Influence of the molecular architecture on the adsorption onto solid surfaces: comb-like polymers.

PubMed

Guzmán, Eduardo; Ortega, Francisco; Prolongo, Margarita G; Starov, Victor M; Rubio, Ramón G

2011-09-28

The processes of adsorption of grafted copolymers onto negatively charged surfaces were studied using a dissipative quartz crystal microbalance (D-QCM) and ellipsometry. The control parameters in the study of the adsorption are the existence or absence on the molecular architecture of grafted polyethyleneglycol (PEG) chains with different lengths and the chemical nature of the main chain, poly(allylamine) (PAH) or poly(L-lysine) (PLL). It was found out that the adsorption kinetics of the polymers showed a complex behavior. The total adsorbed amount depends on the architecture of the polymer chains (length of the PEG chains), on the polymer concentration and on the chemical nature of the main chain. The comparison of the thicknesses of the adsorbed layers obtained from D-QCM and from ellipsometry allowed calculation of the water content of the layers that is intimately related to the grafting length. The analysis of D-QCM results also provides information about the shear modulus of the layers, whose values have been found to be typical of a rubber-like polymer system. It is shown that the adsorption of polymers with a charged backbone is not driven exclusively by the electrostatic interactions, but the entropic contributions as a result of the trapping of water in the layer structure are of fundamental importance.

Gastrointestinal bioavailability of 2.0 nm diameter gold nanoparticles.

PubMed

Smith, Candice A; Simpson, Carrie A; Kim, Ganghyeok; Carter, Carly J; Feldheim, Daniel L

2013-05-28

The use of gold nanoparticles as imaging agents and therapeutic delivery systems is growing rapidly. However, a significant limitation of gold nanoparticles currently is their low absorption efficiencies in the gastrointestinal (GI) tract following oral administration. In an attempt to identify ligands that facilitate gold nanoparticle absorption in the GI tract, we have studied the oral bioavailability of 2.0 nm diameter gold nanoparticles modified with the small molecules p-mercaptobenzoic acid and glutathione, and polyethylene glycols (PEG) of different lengths and charge (neutral and anionic). We show that GI absorption of gold nanoparticles modified with the small molecules tested was undetectable. However, the absorption of PEGs depended upon PEG length, with the shortest PEG studied yielding gold nanoparticle absorptions that are orders-of-magnitude larger than observed previously. As the oral route is the most convenient one for administering drugs and diagnostic reagents, these results suggest that short-chain PEGs may be useful in the design of gold nanoparticles for the diagnosis and treatment of disease.

Association behaviors of dodecyltrimethylammonium bromide with double hydrophilic block co-polymer poly(ethylene glycol)-block-poly(glutamate sodium).

PubMed

Han, Yuchun; Xia, Lin; Zhu, Linyi; Zhang, Shusheng; Li, Zhibo; Wang, Yilin

2012-10-30

The association behaviors of single-chain surfactant dodecyltrimethylammonium bromide (DTAB) with double hydrophilic block co-polymers poly(ethylene glycol)-b-poly(sodium glutamate) (PEG(113)-PGlu(50) or PEG(113)-PGlu(100)) were investigated using isothermal titration microcalorimetry, cryogenic transmission electron microscopy, circular dichroism, ζ potential, and particle size measurements. The electrostatic interaction between DTAB and the oppositely charged carboxylate groups of PEG-PGlu induces the formation of super-amphiphiles, which further self-assemble into ordered aggregates. Dependent upon the charge ratios between DTAB and the glutamic acid residue of the co-polymer, the mixture solutions can change from transparent to opalescent without precipitation. Dependent upon the chain length of the PGlu block, the mixture of DTAB and PEG-PGlu diblocks can form two different aggregates at their corresponding electroneutral point. Spherical and rod-like aggregates are formed in the PEG(113)-PGlu(50)/DTAB mixture, while the vesicular aggregates are observed in the PEG(113)-PGlu(100)/DTAB mixture solution. Because the PEG(113)-PGlu(100)/DTAB super-amphiphile has more hydrophobic components than that of the PEG(113)-PGlu(50)/DTAB super-amphiphile, the former prefers forming the ordered aggregates with higher curvature, such as spherical and rod aggregates, but the latter prefers forming vesicular aggregates with lower curvature.

Influence of Polyethylene Glycol Lipid Desorption Rates on Pharmacokinetics and Pharmacodynamics of siRNA Lipid Nanoparticles

PubMed Central

Mui, Barbara L; Tam, Ying K; Jayaraman, Muthusamy; Ansell, Steven M; Du, Xinyao; Tam, Yuen Yi C; Lin, Paulo JC; Chen, Sam; Narayanannair, Jayaprakash K; Rajeev, Kallanthottathil G; Manoharan, Muthiah; Akinc, Akin; Maier, Martin A; Cullis, Pieter; Madden, Thomas D; Hope, Michael J

2013-01-01

Lipid nanoparticles (LNPs) encapsulating short interfering RNAs that target hepatic genes are advancing through clinical trials, and early results indicate the excellent gene silencing observed in rodents and nonhuman primates also translates to humans. This success has motivated research to identify ways to further advance this delivery platform. Here, we characterize the polyethylene glycol lipid (PEG-lipid) components, which are required to control the self-assembly process during formation of lipid particles, but can negatively affect delivery to hepatocytes and hepatic gene silencing in vivo. The rate of transfer from LNPs to plasma lipoproteins in vivo is measured for three PEG-lipids with dialkyl chains 14, 16, and 18 carbons long. We show that 1.5 mol % PEG-lipid represents a threshold concentration at which the chain length exerts a minimal effect on hepatic gene silencing but can still modify LNPs pharmacokinetics and biodistribution. Increasing the concentration to 2.5 and 3.5 mol % substantially compromises hepatocyte gene knockdown for PEG-lipids with distearyl (C18) chains but has little impact for shorter dimyristyl (C14) chains. These data are discussed with respect to RNA delivery and the different rates at which the steric barrier disassociates from LNPs in vivo. PMID:24345865

Molecular dynamics study of the structure and interparticle interactions of polyethylene glycol-conjugated PAMAM dendrimers.

PubMed

Lee, Hwankyu; Larson, Ronald G

2009-10-08

We performed molecular dynamics (MD) simulations of one or two copies of polyethylene glycol of molecular weight 550 (PEG550) and 5000 (PEG5000) daltons, conjugated to generation 3 (G3) to 5 (G5) polyamidoamine (PAMAM) dendrimers with explicit water using a coarse-grained model. We found the radii of gyration of these dendrimer-PEG molecules to be close to those measured in experiments by Hedden and Bauer (Hedden , R. C. ; Bauer , B. J. Macromolecules 2003 , 36 , 1829.). Densely grafted PEG ligands (>50% of the dendrimer surface) extend like brushes, with layer thickness in agreement with theory for starlike polymers. Two dendrimer-PEG complexes in the box drift away from each other, indicating that no aggregation is induced by either short or long PEG chains, conflicting with a recent view that the cytotoxicity of some PEGylated particles might be due to particle aggregation for long PEG lengths.

[Effect of polyethylene glycol-lipid derivatives on the stability of grafted liposomes].

PubMed

Xu, Yang; Shi, Li; Deng, Yi-hui

2011-10-01

It is reported that polyethylene glycol-lipid (PEG-lipid) derivatives increase liposomes stability, prolong the blood circulation of liposomes, enhance their tumor-targeting efficiency, and improve drug efficacy. Therefore, it is of great importance to investigate the influence of modified PEG-lipid derivatives on the physical, chemical, and biological characteristics of liposomes for the promotion of dealing with the existed problems, such as the accelerated blood clearance (ABC) phenomenon when repeated intravous injection at a certain time-interval, and developing novel targeted pharmaceutical preparations. In this review, the effects of modified PEG-lipid derivatives were summarized in many aspects. It indicats that the chemical bonds (amide, ether, ester, and disulfide) between PEG and lipid, as well as the species of lipids, such as the commonly used phosphatidylethanolamine, cholesterol, and diacylglycerol have substantial effects on the grafted liposomes stability in vitro and in vivo. Besides, the properties of lipids (the fatty acid chain length and saturation) and the groups (methoxy, carboxylic and amino) at the distal ends of the PEG chains were also considered to be important factors. In the end, the influence of the average molecular weight of PEG and the molar ratio of PEG-lipid derivatives in the total lipid were further focused.

Dependence of the product chain-length on detergents for long-chain E-polyprenyl diphosphate synthases

PubMed Central

Pan, Jian-Jung; Ramamoorthy, Gurusankar; Poulter, C. Dale

2013-01-01

Long-chain E-polyprenyl diphosphate synthases (E-PDS) catalyze repetitive addition of isopentenyl diphosphate (IPP) to the growing prenyl chain of an allylic diphosphate. The polyprenyl diphosphate products are required for the biosynthesis of ubiquinones and menaquinones required for electron transport during oxidative phosphorylation to generate ATP. In vitro, the long-chain PDSs require addition of phospholipids or detergents to the assay buffer to enhance product release and maintain efficient turnover. During preliminary assays of product chain-length with anionic, zwitterionic, and non-ionic detergents, we discovered considerable variability. Examination of a series of non-ionic PEG detergents with several long-chain E-PDSs from different organisms revealed that in vitro incubations with nonaethylene glycol monododecyl ether or Triton X-100 typically gave chain lengths that corresponded to those of the isoprenoid moieties in respiratory quinones synthesized in vivo. In contrast incubations in buffer with n-butanol, CHAPS, DMSO, n-octyl-β-glucopyranoside, or β-cyclodextrin or in buffer without detergent typically proceeded more slowly and gave a broad range of chain lengths. PMID:23802587

Influence of Polyethylene Glycol Lipid Desorption Rates on Pharmacokinetics and Pharmacodynamics of siRNA Lipid Nanoparticles.

PubMed

Mui, Barbara L; Tam, Ying K; Jayaraman, Muthusamy; Ansell, Steven M; Du, Xinyao; Tam, Yuen Yi C; Lin, Paulo Jc; Chen, Sam; Narayanannair, Jayaprakash K; Rajeev, Kallanthottathil G; Manoharan, Muthiah; Akinc, Akin; Maier, Martin A; Cullis, Pieter; Madden, Thomas D; Hope, Michael J

2013-12-17

Lipid nanoparticles (LNPs) encapsulating short interfering RNAs that target hepatic genes are advancing through clinical trials, and early results indicate the excellent gene silencing observed in rodents and nonhuman primates also translates to humans. This success has motivated research to identify ways to further advance this delivery platform. Here, we characterize the polyethylene glycol lipid (PEG-lipid) components, which are required to control the self-assembly process during formation of lipid particles, but can negatively affect delivery to hepatocytes and hepatic gene silencing in vivo. The rate of transfer from LNPs to plasma lipoproteins in vivo is measured for three PEG-lipids with dialkyl chains 14, 16, and 18 carbons long. We show that 1.5 mol % PEG-lipid represents a threshold concentration at which the chain length exerts a minimal effect on hepatic gene silencing but can still modify LNPs pharmacokinetics and biodistribution. Increasing the concentration to 2.5 and 3.5 mol % substantially compromises hepatocyte gene knockdown for PEG-lipids with distearyl (C18) chains but has little impact for shorter dimyristyl (C14) chains. These data are discussed with respect to RNA delivery and the different rates at which the steric barrier disassociates from LNPs in vivo.Molecular Therapy-Nucleic Acids (2013) 2, e139; doi:10.1038/mtna.2013.66; published online 17 December 2013.

Elastin-like Polypeptide Linkers for Single-Molecule Force Spectroscopy.

PubMed

Ott, Wolfgang; Jobst, Markus A; Bauer, Magnus S; Durner, Ellis; Milles, Lukas F; Nash, Michael A; Gaub, Hermann E

2017-06-27

Single-molecule force spectroscopy (SMFS) is by now well established as a standard technique in biophysics and mechanobiology. In recent years, the technique has benefitted greatly from new approaches to bioconjugation of proteins to surfaces. Indeed, optimized immobilization strategies for biomolecules and refined purification schemes are being steadily adapted and improved, which in turn has enhanced data quality. In many previously reported SMFS studies, poly(ethylene glycol) (PEG) was used to anchor molecules of interest to surfaces and/or cantilever tips. The limitation, however, is that PEG exhibits a well-known trans-trans-gauche to all-trans transition, which results in marked deviation from standard polymer elasticity models such as the worm-like chain, particularly at elevated forces. As a result, the assignment of unfolding events to protein domains based on their corresponding amino acid chain lengths is significantly obscured. Here, we provide a solution to this problem by implementing unstructured elastin-like polypeptides as linkers to replace PEG. We investigate the suitability of tailored elastin-like polypeptides linkers and perform direct comparisons to PEG, focusing on attributes that are critical for single-molecule force experiments such as linker length, monodispersity, and bioorthogonal conjugation tags. Our results demonstrate that by avoiding the ambiguous elastic response of mixed PEG/peptide systems and instead building the molecular mechanical systems with only a single bond type with uniform elastic properties, we improve data quality and facilitate data analysis and interpretation in force spectroscopy experiments. The use of all-peptide linkers allows alternative approaches for precisely defining elastic properties of proteins linked to surfaces.

Complete regression of xenograft tumors using biodegradable mPEG-PLA-SN38 block copolymer micelles.

PubMed

Lu, Lu; Zheng, Yan; Weng, Shuqiang; Zhu, Wenwei; Chen, Jinhong; Zhang, Xiaomin; Lee, Robert J; Yu, Bo; Jia, Huliang; Qin, Lunxiu

2016-06-01

7-Ethyl-10-hydroxy-comptothecin (SN38) is an active metabolite of irinotecan (CPT-11) and the clinical application of SN38 is limited by its hydrophobicity and instability. To address these issues, a series of novel amphiphilic mPEG-PLA-SN38-conjugates were synthesized by linking SN38 to mPEG-PLA-SA, and they could form micelles by self-assembly. The effects of mPEG-PLA composition were studied in vitro and in vivo. The mean diameters of mPEG2K-PLA-SN38 micelles and mPEG4K-PLA-SN38 micelles were 10-20nm and 120nm, respectively, and mPEG2K-PLA-SN38 micelles showed greater antitumor efficacy than mPEG4K-PLA-SN38 micelles both in vitro and in vivo. These data suggest that the lengths of mPEG and PLA chains had a major impact on the physicochemical characteristics and antitumor activity of SN38-conjugate micelles. Copyright © 2016 Elsevier B.V. All rights reserved.

Influence of dendrimer generation and polyethylene glycol length on the biodistribution of PEGylated dendrimers.

PubMed

Kojima, Chie; Regino, Celeste; Umeda, Yasuhito; Kobayashi, Hisataka; Kono, Kenji

2010-01-04

Dendrimers are a potential drug carrier. Because modification with polyethylene glycol (PEG) is known to improve the blood retention, PEGylated dendrimers have been studied as a useful drug carrier. In this study, three types of PEGylated L-lysine-bearing polyamidoamine dendrimers (PEG2k-Lys-PAMAM (G4), PEG5k-Lys-PAMAM (G4), PEG2k-Lys-PAMAM (G5)) were synthesized, which are composed of a dendrimer of different generations (generations 4 and 5) and PEG chains with different molecular weights (2k and 5k). An acetylated L-lysine-bearing dendrimer was also synthesized as a non-PEGylated dendrimer. Bifunctional diethylenetriaminepentaacetic acid (pSCN-benzyl-DTPA) was bound to the epsilon -amino group of lysine in a dendrimer, to be labeled with radioactive indium-111. These PEGylayed dendrimers showed longer blood retention and lower accumulation in other normal organs such as the kidneys than the non-PEGylated dendrimer. The PEGylated dendrimers with the higher generation and the longer PEG led the greater blood retention.

Monoglyceride-based self-assembling copolymers as carriers for poorly water-soluble drugs.

PubMed

Rouxhet, L; Dinguizli, M; Latere Dwan'isa, J P; Ould-Ouali, L; Twaddle, P; Nathan, A; Brewster, M E; Rosenblatt, J; Ariën, A; Préat, V

2009-12-01

To develop self-assembling polymers forming polymeric micelles and increasing the solubility of poorly soluble drugs, amphiphilic polymers containing a hydrophilic PEG moiety and a hydrophobic moiety derived from monoglycerides and polyethers were designed. The biodegradable copolymers were obtained via a polycondensation reaction of polyethylene glycol (PEG), monooleylglyceride (MOG) and succinic anhydride (SA). Polymers with molecular weight below 10,000 g/mol containing a minimum of 40 mol% PEG and a maximum of 10 mol% MOG self-assembled spontaneously in aqueous media upon gentle mixing. They formed particles with a diameter of 10 nm although some aggregation was evident. The critical micellar concentration varied between 3x10(-4) and 4x10(-3) g/ml, depending on the polymer. The cloud point (> or = 66 degrees C) and flocculation point (> or = 0.89 M) increased with the PEG chain length. At a 1% concentration, the polymers increased the solubility of poorly water-soluble drug candidates up to 500-fold. Drug solubility increased as a function of the polymer concentration. HPMC capsules filled with these polymers disintegrated and released model drugs rapidly. Polymer with long PEG chains had a lower cytotoxicity (MTT test) on Caco-2 cells. All of these data suggest that the object polymers, in particular PEG1000/MOG/SA (45/5/50) might be potential candidates for improving the oral biopharmaceutical performance of poorly soluble drugs.

Laser synthesis of aluminium nanoparticles in biocompatible polymer solutions

NASA Astrophysics Data System (ADS)

Singh, Rina; Soni, R. K.

2014-08-01

Pulsed laser ablation of Aluminium (Al) in pure water rapidly forms a thin alumina (Al2O3) layer which drastically modifies surface plasmon resonance (SPR) absorption characteristics in deep-UV region. Initially, pure aluminium nanoparticles (NPs) are generated in water without any stabilizers or surfactants at low laser fluence which gradually transform to stable Al-Al2O3 core-shell nanostructure with increasing either residency time or fluence. The role of laser wavelength and fluence on the SPR properties and oxidation characteristics of Al NPs has been investigated in detail. We also present a one-step in situ synthesis of oxide-free stable Al NPs in biocompatible polymer solutions using laser ablation in liquid method. We have used nonionic polymers (PVP, PVA and PEG) and anionic surfactant (SDS) stabilizer to suppress the Al2O3 formation and studied the effect of polymer functional group, polymeric chain length, polymer concentration and anionic surfactant on the incipient embryonic aluminium particles and their sizes. The different functional groups of polymers resulted in different oxidation states of Al. PVP and PVA polymers resulted in pure Al NPs; however, PEG and SDS resulted in alumina-modified Al NPs. The Al nanoparticles capped with PVP, PVA, and PEG show a good correlation between nanoparticle stability and monomeric length of the polymer chain.

How PEGylation enhances the stability and potency of insulin: a molecular dynamics simulation.

PubMed

Yang, Cheng; Lu, Diannan; Liu, Zheng

2011-04-05

While the effectiveness of PEGylation in enhancing the stability and potency of protein pharmaceuticals has been validated for years, the underlying mechanism remains poorly understood, particularly at the molecular level. A molecular dynamics simulation was developed using an annealing procedure that allowed an all-atom level examination of the interaction between PEG polymers of different chain lengths and a conjugated protein represented by insulin. It was shown that PEG became entangled around the protein surface through hydrophobic interaction and concurrently formed hydrogen bonds with the surrounding water molecules. In addition to enhancing its structural stability, as indicated by the root-mean-square difference (rmsd) and secondary structure analyses, conjugation increased the size of the protein drug while decreasing the solvent accessible surface area of the protein. All these thus led to prolonged circulation life despite kidney filtration, proteolysis, and immunogenic side effects, as experimentally demonstrated elsewhere. Moreover, the simulation results indicated that an optimal chain length exists that would maximize drug potency underpinned by the parameters mentioned above. The simulation provided molecular insight into the interaction between PEG and the conjugated protein at the all-atom level and offered a tool that would allow for the design of PEGylated protein pharmaceuticals for given applications.

Thermosensitive mPEG-b-PA-g-PNIPAM comb block copolymer micelles: effect of hydrophilic chain length and camptothecin release behavior.

PubMed

Yang, Xiao-Li; Luo, Yan-Ling; Xu, Feng; Chen, Ya-Shao

2014-02-01

Block copolymer micelles are extensively used as drug controlled release carriers, showing promising application prospects. The comb or brush copolymers are especially of great interest, whose densely-grafted side chains may be important for tuning the physicochemical properties and conformation in selective solvents, even in vitro drug release. The purpose of this work was to synthesize novel block copolymer combs via atom transfer radical polymerization, to evaluate its physicochemical features in solution, to improve drug release behavior and to enhance the bioavailablity, and to decrease cytotoxicity. The physicochemical properties of the copolymer micelles were examined by modulating the composition and the molecular weights of the building blocks. A dialysis method was used to load hydrophobic camptothecin (CPT), and the CPT release and stability were detected by UV-vis spectroscopy and high-performance liquid chromatography, and the cytotoxicity was evaluated by MTT assays. The copolymers could self-assemble into well-defined spherical core-shell micelle aggregates in aqueous solution, and showed thermo-induced micellization behavior, and the critical micelle concentration was 2.96-27.64 mg L(-1). The micelles were narrow-size-distribution, with hydrodynamic diameters about 128-193 nm, depending on the chain length of methoxy polyethylene glycol (mPEG) blocks and poly(N-isopropylacrylamide) (PNIPAM) graft chains or/and compositional ratios of mPEG to PNIPAM. The copolymer micelles could stably and effectively load CPT but avoid toxicity and side-effects, and exhibited thermo-dependent controlled and targeted drug release behavior. The copolymer micelles were safe, stable and effective, and could potentially be employed as CPT controlled release carriers.

Molecular dynamics studies of polyethylene oxide and polyethylene glycol: hydrodynamic radius and shape anisotropy.

PubMed

Lee, Hwankyu; Venable, Richard M; Mackerell, Alexander D; Pastor, Richard W

2008-08-01

A revision (C35r) to the CHARMM ether force field is shown to reproduce experimentally observed conformational populations of dimethoxyethane. Molecular dynamics simulations of 9, 18, 27, and 36-mers of polyethylene oxide (PEO) and 27-mers of polyethylene glycol (PEG) in water based on C35r yield a persistence length lambda = 3.7 A, in quantitative agreement with experimentally obtained values of 3.7 A for PEO and 3.8 A for PEG; agreement with experimental values for hydrodynamic radii of comparably sized PEG is also excellent. The exponent upsilon relating the radius of gyration and molecular weight (R(g) proportional, variantM(w)(upsilon)) of PEO from the simulations equals 0.515 +/- 0.023, consistent with experimental observations that low molecular weight PEG behaves as an ideal chain. The shape anisotropy of hydrated PEO is 2.59:1.44:1.00. The dimension of the middle length for each of the polymers nearly equals the hydrodynamic radius R(h)obtained from diffusion measurements in solution. This explains the correspondence of R(h) and R(p), the pore radius of membrane channels: a polymer such as PEG diffuses with its long axis parallel to the membrane channel, and passes through the channel without substantial distortion.

Avidin-biotin-PEG-CPA complexes as potential EPR-directed therapeutic protein carriers: preparation and characterization.

PubMed

Ke, Shan; Wright, John C; Kwon, Glen S

2007-01-01

Bovine carboxypeptidase A (CPA) conjugated with biotinylated poly(ethylene glycol) (PEG) has been synthesized and characterized in terms of stoichiometry and half-life of the avidin-biotin-PEG(s)-CPA complex. The half-lives for dissociation are 3.34 days for the avidin-biotin-PEG(3400)-CPA 1:1 complex, 3.65 days for the avidin-biotin-PEG(5000)-CPA 1:1 complex, 3.91 days for the avidin-biotin-PEG(3400)-CPA-PEG(2000) 1:1 complex, and 2.74 days for the avidin-biotin-PEG(5000)-CPA-PEG(2000) 1:1 complex. The slow dissociation demonstrates the stability of complexes using a PEGylated biotin terminus as a linker with avidin. The stoichiometry of the biotin-PEGylated CPA with avidin was determined by the 2,6-ANS method, and the results are consistent with measurements of the stoichiometry using size exclusion chromatography. The stoichiometries are 1:2 for the avidin-biotin-PEG(3400)-CPA complex and the avidin-biotin-PEG(3400)-CPA-PEG(2000) complex, 1:1 for the avidin-biotin-PEG(5000)-CPA complex, and 1:4 for the avidin-biotin-PEG(5000)-CPA-PEG(2000) complex. These findings stress both the importance of the length of a PEG chain as an appropriate spacer between the biotin terminus and a functional group, and the great potential of the avidin-biotin-PEGylated-protein complex as a therapeutic protein delivery system for solid tumor prodrug targeting.

Aqueous biphasic systems containing PEG-based deep eutectic solvents for high-performance partitioning of RNA.

PubMed

Zhang, Hongmei; Wang, Yuzhi; Zhou, Yigang; Xu, Kaijia; Li, Na; Wen, Qian; Yang, Qin

2017-08-01

In this work, 16 kinds of novel deep eutectic solvents (DESs) composed of polyethylene glycol (PEG) and quaternary ammonium salts, were coupled with Aqueous Biphasic Systems (ABSs) to extract RNA. The phase forming ability of ABSs were comprehensively evaluated, involving the effects of various proportions of DESs' components, carbon chain length and anions species of quaternary ammonium salts, average molecular weights of PEG and inorganic salts nature. Then the systems were applied in RNA extraction, and the results revealed that the extraction efficiency values were distinctly enhanced by relatively lower PEG content in DESs, smaller PEG molecular weights, longer carbon chain of quaternary ammonium salts and more hydrophobic inorganic salts. Then the systems composed of [TBAB][PEG600] and Na 2 SO 4 were utilized in the influence factor experiments, proving that the electrostatic interaction was the dominant force for RNA extraction. Therefore, back-extraction efficiency values ranging between 85.19% and 90.78% were obtained by adjusting the ionic strength. Besides, the selective separation of RNA and tryptophane (Trp) was successfully accomplished. It was found that 86.19% RNA was distributed in the bottom phase, while 72.02% Trp was enriched in the top phase in the novel ABSs. Finally, dynamic light scattering (DLS) and transmission electron microscope (TEM) were used to further investigate the extraction mechanism. The proposed method reveals the outstanding feasibility of the newly developed ABSs formed by PEG-based DESs and inorganic salts for the green extraction of RNA. Copyright © 2017 Elsevier B.V. All rights reserved.

Poly(l-glutamic acid)-g-poly(ethylene glycol) external layer in polyelectrolyte multilayer films: Characterization and resistance to serum protein adsorption.

PubMed

Szczepanowicz, Krzysztof; Kruk, Tomasz; Świątek, Wiktoria; Bouzga, Aud M; Simon, Christian R; Warszyński, Piotr

2018-06-01

Formation of protein-resistant surfaces is a major challenge in the design of novel biomaterials and an important strategy to prevent protein adsorption is the formation of protein-resistant coatings. It can be achieved by proper modification of surfaces, e.g., by immobilization of hydrophilic polymers such as poly(ethylene glycol) (PEG). An appropriate method to immobilize PEG at charged surfaces is the adsorption of copolymers with PEG chains grafted onto polyelectrolyte backbone. The growing interest in the use of polyelectrolyte multilayer coatings in biomedical applications to improve biocompatibility and/or to prepare coating with antiadhesive properties has been the main reason for these studies. Therefore the aim was to produce protein resistant polyelectrolyte multilayer films. They were formed via the layer-by-layer approach, while their pegylation by the deposition of pegylated polyanion, PGA-g-PEG, as an external layer. The influence of PEG chain length and grafting density of PGA-g-PEG copolymers on the protein antiadhesive properties of pegylated polyelectrolyte multilayer films was investigated. To monitor the formation of pegylated and non-pegylated multilayer films, adsorption of the following proteins: HSA, Fibrinogen, and FBS were measured by quartz crystal microbalance (QCM - D). We found that protein adsorption onto all pegylated polyelectrolyte multilayers was significantly reduced in comparison to non-pegylated ones. Long-term performance tests confirmed the stability and the durability of the protein resistant properties of the pegylated multilayers. Antiadhesive properties of tested surfaces pegylated by PGA-g-PEG were compared to the available data for pegylated polycation PLL-g-PEG. Copyright © 2018 Elsevier B.V. All rights reserved.

Pharmacokinetics, biodistribution and in vivo efficacy of cisplatin loaded poly(L-glutamic acid)-g-methoxy poly(ethylene glycol) complex nanoparticles for tumor therapy.

PubMed

Yu, Haiyang; Tang, Zhaohui; Zhang, Dawei; Song, Wantong; Zhang, Ying; Yang, Yan; Ahmad, Zaheer; Chen, Xuesi

2015-05-10

Platinum-based polymeric nano-drugs, especially cisplatin-loaded polymeric nanoparticles (CDDP-NPs), have been extensively exploited for the treatment of solid tumors. However, it is still unclear what role the processing procedure and the properties of the polymeric carrier materials may play in influencing the plasma pharmacokinetics, biodistribution and in vivo efficacy of CDDP-NPs. In this study, a series of poly(l-glutamic acid)-g-methoxy poly(ethylene glycol) (PLG-g-mPEG) copolymers were synthesized for the preparation of CDDP-loaded PLG-g-mPEG (CDDP/PLG-g-mPEG) nanoparticles. All of the parameters, including PLG molecular weight, mPEG/PLG weight ratio, mPEG chain length, ultrafiltration purification and cisplatin loading content, were found to have a significant influence on the plasma pharmacokinetics of the CDDP/PLG-g-mPEG nanoparticles. The blood circulation time of the nanoparticles was prolonged with increases in PLG molecular weight, mPEG/PLG weight ratio, mPEG chain length and CDDP loading content. The use of ultrafiltration purification could prolong the blood circulation time of the nanoparticles as well. Experiments to measure the pharmacokinetics and biodistribution demonstrated that the selected CDDP/PLG-g-mPEG nanoparticles, NP10, had a long blood circulation time and could achieve selective and significant accumulation in Lewis lung carcinoma (LLC) tumors. The platinum plasma concentrations in the LLC tumor-bearing mice receiving NP10 remained up to 46-fold higher than that of mice receiving equivalent doses of free CDDP. In addition, the plasma area under the concentration time curve (AUC) of NP10 was 31-fold higher than that of free CDDP in 48h. The platinum concentration ratio of NP10 to free CDDP in tumors reached as high as 9.4. The tumor AUC ratio of NP10 to CDDP was 6. Using a mouse C26 tumor model, here we demonstrate that NP10 improves the safety and tolerance in vivo when compared to CDDP and effectively inhibits the growth of C26 tumors. Furthermore, increasing the dosage of NP10 by 2 or 3-fold of free CCDP improved its anticancer efficacy to comparable or higher levels. These results indicate that CDDP/PLG-g-mPEG nanoparticles have greater potential for the treatment of solid tumors in clinical application. Copyright © 2014 Elsevier B.V. All rights reserved.

Surface phase behavior and microstructure of lipid/PEG-emulsifier monolayer-coated microbubbles.

PubMed

Borden, Mark A; Pu, Gang; Runner, Gabriel J; Longo, Marjorie L

2004-06-01

Langmuir trough methods and fluorescence microscopy were combined to investigate the phase behavior and microstructure of monolayer shells coating micron-scale bubbles (microbubbles) typically used in biomedical applications. The monolayer shell consisted of a homologous series of saturated acyl chain phospholipids and an emulsifier containing a single hydrophobic stearate chain and polyethylene glycol (PEG) head group. PEG-emulsifier was fully miscible with expanded phase lipids and phase separated from condensed phase lipids. Phase coexistence was observed in the form of dark condensed phase lipid domains surrounded by a sea of bright, emulsifier-rich expanded phase. A rich assortment of condensed phase area fractions and domain morphologies, including networks and other novel structures, were observed in each batch of microbubbles. Network domains were reproduced in Langmuir monolayers under conditions of heating-cooling followed by compression-expansion, as well as in microbubble shells that underwent surface flow with slight compression. Domain size decreased with increased cooling rate through the phase transition temperature, and domain branching increased with lipid acyl chain length at high cooling rates. Squeeze-out of the emulsifier at a surface pressure near 35 mN/m was indicated by a plateau in Langmuir isotherms and directly visualized with fluorescence microscopy, although collapse of the solid lipid domains occurred at much higher surface pressures. Compression of the monolayer past the PEG-emulsifier squeeze-out surface pressure resulted in a dark shell composed entirely of lipid. Under certain conditions, the PEG-emulsifier was reincorporated upon subsequent expansion. Factors that affect shell formation and evolution, as well as implications for the rational design of microbubbles in medical applications, are discussed.

Fabrication of honeycomb-structured poly(ethylene glycol)-block-poly(lactic acid) porous films and biomedical applications for cell growth

NASA Astrophysics Data System (ADS)

Yao, Bingjian; Zhu, Qingzeng; Yao, Linli; Hao, Jingcheng

2015-03-01

A series of poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) copolymers with a hydrophobic PLA block of different molecular weights and a fixed length hydrophilic PEG were synthesized successfully and characterized. These amphiphilic block copolymers were used to fabricate honeycomb-structured porous films using the breath figure (BF) templating technique. The surface topology and composition of the highly ordered pattern film were further characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and fluorescence microscopy. The results indicated that the PEG-to-PLA block molecular weight ratio influenced the BF film surface topology. The film with the best ordered pores was obtained with a PEG-to-PLA ratio of 2.0 × 103:3.0 × 104. The self-organization of the hydrophilic PEG chains within the pores was confirmed by XPS and fluorescence labeled PEG. A model is proposed to elucidate the stabilization process of the amphiphilic PEG-PLA aggregated architecture on the water droplet-based templates. In addition, GFP-U87 cell viability has been investigated by MTS test and the cell morphology on the honeycomb-structured PEG-PLA porous film has been evaluated using phase-contrast microscope. This porous film is shown to be suitable as a matrix for cell growth.

Use of read-across and computer-based predictive analysis for the safety assessment of PEG cocamines.

PubMed

Skare, Julie A; Blackburn, Karen; Wu, Shengde; Re, Thomas A; Duche, Daniel; Ringeissen, Stephanie; Bjerke, Donald L; Srinivasan, Viny; Eisenmann, Carol

2015-04-01

In the European Union animal testing has been eliminated for cosmetic ingredients while the US Cosmetic Ingredient Review Expert Panel may request data from animal studies. The use of read-across and predictive toxicology provides a path for filling data gaps without additional animal testing. The PEG cocamines are tertiary amines with an alkyl group derived from coconut fatty acids and two PEG chains of varying length. Toxicology data gaps for the PEG cocamines can be addressed by read-across based on structure-activity relationship using the framework described by Wu et al. (2010) for identifying suitable structural analogs. Data for structural analogs supports the conclusion that the PEG cocamines are non-genotoxic and not expected to exhibit systemic or developmental/reproductive toxicity with use in cosmetics. Due to lack of reliable dermal sensitization data for suitable analogs, this endpoint was addressed using predictive software (TIMES SS) as a first step (Laboratory of Mathematical Chemistry). The prediction for PEG cocamines was the same as that for PEGs, which have been concluded to not present a significant concern for dermal sensitization. This evaluation for PEG cocamines demonstrates the utility of read-across and predictive toxicology tools to assess the safety of cosmetic ingredients. Copyright © 2015 Elsevier Inc. All rights reserved.

A Study on the Impact of Poly(3-hexylthiophene) Chain Length and Other Applied Side-Chains on the NO2 Sensing Properties of Conducting Graft Copolymers

PubMed Central

Kepska, Kinga

2018-01-01

The detection and concentration measurements of low concentrations of nitrogen dioxide (NO2) are important because of its negative effects on human health and its application in many fields of industry and safety systems. In our approach, conducting graft copolymers based on the poly(3-hexylthiophene) (P3HT) conducting polymer and other side-chains, polyethylene glycol (PEG) and dodec-1-en, grafted on a poly(methylhydrosiloxane) backbone, were investigated. The grafts containing PEG (PEGSil) and dodec-1-en (DodecSil) in two variants, namely, fractions with shorter (hexane fraction -H) and longer (chloroform fraction -CH) side-chains of P3HT, were tested as receptor structures in NO2 gas sensors. Their responses to NO2, within the concentration range of 1–20 ppm, were investigated in an nitrogen atmosphere at different operating temperatures—room temperature (RT) = 25 °C, 50 °C, and 100 °C. The results indicated that both of the copolymers with PEG side-chains had higher responses to NO2 than the materials with dodec-1-en side-chains. Furthermore, the results indicated that, in both cases, H fractions were more sensitive than CH fractions. The highest response to 1 ppm of NO2, from the investigated graft copolymers, had PEGSil H, which indicated a response of 1330% at RT and 1980% at 100 °C. The calculated lower-limit of the detection of this material is lower than 300 ppb of NO2 at 100 °C. This research indicated that graft copolymers of P3HT had great potential for low temperature NO2 sensing, and that the proper choice of other side-chains in graft copolymers can improve their gas sensing properties. PMID:29558448

Infrared spectroscopic study of thermotropic phase behavior of newly developed synthetic biopolymers

NASA Astrophysics Data System (ADS)

Bista, Rajan K.; Bruch, Reinhard F.; Covington, Aaron M.

2011-10-01

The thermotropic phase behavior of a suite of newly developed self-forming synthetic biopolymers has been investigated by variable-temperature Fourier transform infrared (FT-IR) absorption spectroscopy. The temperature-induced infrared spectra of these artificial biopolymers (lipids) composed of 1,2-dimyristoyl- rac-glycerol-3-dodecaethylene glycol (GDM-12), 1,2-dioleoyl- rac-glycerol-3-dodecaethylene glycol (GDO-12) and 1,2-distearoyl- rac-glycerol-3-triicosaethylene glycol (GDS-23) in the spectral range of 4000-500 cm -1 have been acquired by using a thin layered FT-IR spectrometer in conjunction with a custom built temperature-controlled demountable liquid cell having a pathlength of ˜15 μm. The lipids under consideration have long hydrophobic acyl chains and contain various units of hydrophilic polyethylene glycol (PEG) headgroups. In contrast to conventional phospholipids, this new kind of lipids forms liposomes or nanovesicles spontaneously upon hydration, without requiring external activation energy. We have found that the thermal stability of the PEGylated lipids differs greatly depending upon the acyl chain-lengths as well as the nature of the associated bonds and the number of PEG headgroup units. In particular, GDM-12 (saturated 14 hydrocarbon chains with 12 units of PEG headgroup) exhibits one sharp order-disorder phase transition over a temperature range increasing from 3 °C to 5 °C. Similarly, GDS-23 (saturated 18 hydrocarbon chains with 23 units of PEG headgroup) displays comparatively broad order-disorder phase transition profiles between temperature 17 °C and 22 °C. In contrast, GDO-12 (monounsaturated 18 hydrocarbon chains with 12 units of PEG headgroup) does not reveal any order-disorder transition phenomena demonstrating a highly disordered behavior for the entire temperature range. To confirm these observations, differential scanning calorimetry (DSC) was applied to the samples and revealed good agreement with the infrared spectroscopy results. Finally, the investigation of thermal properties of lipids is extremely critical for numerous purposes and the result obtained in this work may find application in various studies including the development of PEGylated lipid based novel drug and substances delivery vehicles.

PEG-protein interaction induced contraction of NalD chains.

PubMed

Yu, Jiyan; Chen, Weizhong; Wu, Chi; Chen, Hao

2014-01-01

In a recent attempt to crystallize a regulator of MexAB-OprM multi-drug efflux systems in Pseudomonas aeruginosa (NalD), we found that adding polyethylene glycol (PEG3350, Mw = 3,350 g/mol) into the protein solution increases the speed of NalD migration in gel electrophoresis, signaling a smaller hydrodynamic size. At first we conjectured that NalD was degraded unexpectedly by PEG; however, we found that there was no change in its molar mass by MALDI-TOF characterization. Moreover, we found that adding polyacrylic acid (PAA) into the solution mixture returned the NalD migration to its normal speed. Furthermore, our analytic ultracentrifugation and dynamic laser light scattering results directly reveal that NalD interacts with PEG so that individual NalD chains gradually shrink as more PEG chains are added in the range of 10-50 mg/mL. Size exclusion chromatography also confirms that the NalD chain shrinks in the presence of PEG. A combination of these results indicates that PEG3350 chains can complex with NalD to induce an intra-protein chain contraction, presumably via the formation of hydrogen bond between -C-O-C- on PEG and -COOH on NalD, resulting in a smaller hydrodynamic size (faster migration) and a higher apparent molar mass. Note that because the presence of PEG affects osmotic pressure, it is considered to be a precipitator of protein crystallization. Our current finding reveals that the interaction of PEG/protein may play a significant role in protein crystallization. The complexation potentially makes the protein chain segments less flexible, and consequently makes crystallization easier. Hopefully, our current results will stimulate further studies in this direction.

PEG-Protein Interaction Induced Contraction of NalD Chains

PubMed Central

Yu, Jiyan; Chen, Weizhong; Wu, Chi; Chen, Hao

2014-01-01

In a recent attempt to crystallize a regulator of MexAB-OprM multi-drug efflux systems in Pseudomonas aeruginosa (NalD), we found that adding polyethylene glycol (PEG3350, Mw = 3,350 g/mol) into the protein solution increases the speed of NalD migration in gel electrophoresis, signaling a smaller hydrodynamic size. At first we conjectured that NalD was degraded unexpectedly by PEG; however, we found that there was no change in its molar mass by MALDI-TOF characterization. Moreover, we found that adding polyacrylic acid (PAA) into the solution mixture returned the NalD migration to its normal speed. Furthermore, our analytic ultracentrifugation and dynamic laser light scattering results directly reveal that NalD interacts with PEG so that individual NalD chains gradually shrink as more PEG chains are added in the range of 10–50 mg/mL. Size exclusion chromatography also confirms that the NalD chain shrinks in the presence of PEG. A combination of these results indicates that PEG3350 chains can complex with NalD to induce an intra-protein chain contraction, presumably via the formation of hydrogen bond between –C-O-C– on PEG and –COOH on NalD, resulting in a smaller hydrodynamic size (faster migration) and a higher apparent molar mass. Note that because the presence of PEG affects osmotic pressure, it is considered to be a precipitator of protein crystallization. Our current finding reveals that the interaction of PEG/protein may play a significant role in protein crystallization. The complexation potentially makes the protein chain segments less flexible, and consequently makes crystallization easier. Hopefully, our current results will stimulate further studies in this direction. PMID:24810951

Tough stimuli-responsive supramolecular hydrogels with hydrogen-bonding network junctions.

PubMed

Guo, Mingyu; Pitet, Louis M; Wyss, Hans M; Vos, Matthijn; Dankers, Patricia Y W; Meijer, E W

2014-05-14

Hydrogels were prepared with physical cross-links comprising 2-ureido-4[1H]-pyrimidinone (UPy) hydrogen-bonding units within the backbone of segmented amphiphilic macromolecules having hydrophilic poly(ethylene glycol) (PEG). The bulk materials adopt nanoscopic physical cross-links composed of UPy-UPy dimers embedded in segregated hydrophobic domains dispersed within the PEG matrix as comfirmed by cryo-electron microscopy. The amphiphilic network was swollen with high weight fractions of water (w(H2O) ≈ 0.8) owing to the high PEG weight fraction within the pristine polymers (w(PEG) ≈ 0.9). Two different PEG chain lengths were investigated and illustrate the corresponding consequences of cross-link density on mechanical properties. The resulting hydrogels exhibited high strength and resilience upon deformation, consistent with a microphase separated network, in which the UPy-UPy interactions were adequately shielded within hydrophobic nanoscale pockets that maintain the network despite extensive water content. The cumulative result is a series of tough hydrogels with tunable mechanical properties and tractable synthetic preparation and processing. Furthermore, the melting transition of PEG in the dry polymer was shown to be an effective stimulus for shape memory behavior.

Thermosensitive behavior of poly(ethylene glycol)-based block copolymer (PEG-b-PADMO) controlled via self-assembled microstructure.

PubMed

Cui, Qianling; Wu, Feipeng; Wang, Erjian

2011-05-19

Stimuli-responsive, well-defined diblock copolymers (PEG-b-PADMO) comprising poly(ethylene glycol) (PEG, DP (degree of polymerization)=45) as the hydrophilic and temperature-sensitive part and poly(N-acryloyl-2,2-dimethyl-1,3-oxazolidine) (PADMO, DP=18-47) as the hydrophobic and acid-labile part self-assembled in water into spherical micelles with high aggregation number. The micellar structures and thermally induced phase transitions of the copolymers were investigated with (1)H NMR spectroscopy, light scattering, microscopy, turbidimetry, and fluorescence techniques. Thermoresponsive phase transitions of the copolymers in water were controlled via formation of core-shell-type micelles with densely compact PEG corona. Their lower critical solution temperatures (LCSTs) were modulated within the range 40-72 °C by varying PADMO block length. This unusually low LCST was attributed to the densely packed PEG structure in the polymer micelles, which resulted in strong n-clustering attractive interactions and insufficient hydration of PEG chains in the shell and greatly enhanced the thermosensitivity. The LCST behavior can also be modulated by partial acid hydrolysis of PADMO segments through the resulting change of hydrophobicity. © 2011 American Chemical Society

A brush-polymer conjugate of exendin-4 reduces blood glucose for up to five days and eliminates poly(ethylene glycol) antigenicity

PubMed Central

Qi, Yizhi; Simakova, Antonina; Ganson, Nancy J.; Li, Xinghai; Luginbuhl, Kelli M.; Özer, Imran; Liu, Wenge; Hershfield, Michael S.; Matyjaszewski, Krzysztof; Chilkoti, Ashutosh

2017-01-01

The delivery of therapeutic peptides and proteins is often challenged by a short half-life, and thus the need for frequent injections that limit efficacy, reduce patient compliance and increase treatment cost. Here, we demonstrate that a single subcutaneous injection of site-specific (C-terminal) conjugates of exendin-4 (exendin) — a therapeutic peptide that is clinically used to treat type 2 diabetes — and poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA) with precisely controlled molecular weights lowered blood glucose for up to 120 h in fed mice. Most notably, we show that an exendin-C-POEGMA conjugate with an average of 9 side-chain ethylene glycol (EG) repeats exhibits significantly lower reactivity towards patient-derived anti-poly(ethylene glycol) (PEG) antibodies than two FDA-approved PEGylated drugs, and that reducing the side-chain length to 3 EG repeats completely eliminates PEG antigenicity without compromising in vivo efficacy. Our findings establish the site-specific conjugation of POEGMA as a next-generation PEGylation technology for improving the pharmacological performance of traditional PEGylated drugs, whose safety and efficacy are hindered by pre-existing anti-PEG antibodies in patients. PMID:28989813

PEG-lipid micelles enable cholesterol efflux in Niemann-Pick Type C1 disease-based lysosomal storage disorder

PubMed Central

Brown, Anna; Patel, Siddharth; Ward, Carl; Lorenz, Anna; Ortiz, Mauren; DuRoss, Allison; Wieghardt, Fabian; Esch, Amanda; Otten, Elsje G.; Heiser, Laura M.; Korolchuk, Viktor I.; Sun, Conroy; Sarkar, Sovan; Sahay, Gaurav

2016-01-01

2-Hydroxy-propyl-β-cyclodextrin (HPβCD), a cholesterol scavenger, is currently undergoing Phase 2b/3 clinical trial for treatment of Niemann Pick Type C-1 (NPC1), a fatal neurodegenerative disorder that stems from abnormal cholesterol accumulation in the endo/lysosomes. Unfortunately, the extremely high doses of HPβCD required to prevent progressive neurodegeneration exacerbates ototoxicity, pulmonary toxicity and autophagy-based cellular defects. We present unexpected evidence that a poly (ethylene glycol) (PEG)-lipid conjugate enables cholesterol clearance from endo/lysosomes of Npc1 mutant (Npc1−/−) cells. Herein, we show that distearyl-phosphatidylethanolamine-PEG (DSPE-PEG), which forms 12-nm micelles above the critical micelle concentration, accumulates heavily inside cholesterol-rich late endosomes in Npc1−/− cells. This potentially results in cholesterol solubilization and leakage from lysosomes. High-throughput screening revealed that DSPE-PEG, in combination with HPβCD, acts synergistically to efflux cholesterol without significantly aggravating autophagy defects. These well-known excipients can be used as admixtures to treat NPC1 disorder. Increasing PEG chain lengths from 350 Da-30 kDa in DSPE-PEG micelles, or increasing DSPE-PEG content in an array of liposomes packaged with HPβCD, improved cholesterol egress, while Pluronic block copolymers capable of micelle formation showed slight effects at high concentrations. We postulate that PEG-lipid based nanocarriers can serve as bioactive drug delivery systems for effective treatment of lysosomal storage disorders. PMID:27572704

PEG-lipid micelles enable cholesterol efflux in Niemann-Pick Type C1 disease-based lysosomal storage disorder

NASA Astrophysics Data System (ADS)

Brown, Anna; Patel, Siddharth; Ward, Carl; Lorenz, Anna; Ortiz, Mauren; Duross, Allison; Wieghardt, Fabian; Esch, Amanda; Otten, Elsje G.; Heiser, Laura M.; Korolchuk, Viktor I.; Sun, Conroy; Sarkar, Sovan; Sahay, Gaurav

2016-08-01

2-Hydroxy-propyl-β-cyclodextrin (HPβCD), a cholesterol scavenger, is currently undergoing Phase 2b/3 clinical trial for treatment of Niemann Pick Type C-1 (NPC1), a fatal neurodegenerative disorder that stems from abnormal cholesterol accumulation in the endo/lysosomes. Unfortunately, the extremely high doses of HPβCD required to prevent progressive neurodegeneration exacerbates ototoxicity, pulmonary toxicity and autophagy-based cellular defects. We present unexpected evidence that a poly (ethylene glycol) (PEG)-lipid conjugate enables cholesterol clearance from endo/lysosomes of Npc1 mutant (Npc1-/-) cells. Herein, we show that distearyl-phosphatidylethanolamine-PEG (DSPE-PEG), which forms 12-nm micelles above the critical micelle concentration, accumulates heavily inside cholesterol-rich late endosomes in Npc1-/- cells. This potentially results in cholesterol solubilization and leakage from lysosomes. High-throughput screening revealed that DSPE-PEG, in combination with HPβCD, acts synergistically to efflux cholesterol without significantly aggravating autophagy defects. These well-known excipients can be used as admixtures to treat NPC1 disorder. Increasing PEG chain lengths from 350 Da-30 kDa in DSPE-PEG micelles, or increasing DSPE-PEG content in an array of liposomes packaged with HPβCD, improved cholesterol egress, while Pluronic block copolymers capable of micelle formation showed slight effects at high concentrations. We postulate that PEG-lipid based nanocarriers can serve as bioactive drug delivery systems for effective treatment of lysosomal storage disorders.

Eco-friendly PEG-based controlled release nano-formulations of Mancozeb: Synthesis and bioefficacy evaluation against phytopathogenic fungi Alternaria solani and Sclerotium rolfsii.

PubMed

Majumder, Sujan; Shakil, Najam A; Kumar, Jitendra; Banerjee, Tirthankar; Sinha, Parimal; Singh, Braj B; Garg, Parul

2016-12-01

Controlled release (CR) nano-formulations of Mancozeb (manganese-zinc double salt of N,N-bisdithiocarbamic acid), a protective fungicide, have been prepared using laboratory-synthesized poly(ethylene glycols) (PEGs)-based functionalized amphiphilic copolymers without using any surfactants or external additives. The release kinetics of the developed Mancozeb CR formulations were studied and compared with that of commercially available 42% suspension concentrate and 75% wettable powder. Maximum amount of Mancozeb was released on 42nd day for PEG-600 and octyl chain, PEG-1000 and octyl chain, and PEG-600 and hexadecyl chain, on 35th day for PEG-1000 and hexadecyl chain, on 28th day for PEG-1500 and octyl chain, PEG-2000 and octyl chain, PEG-1500 and hexadecyl chain, and PEG-2000 and hexadecyl chain in comparison to both commercial formulations (15th day). The diffusion exponent (n value) of Mancozeb in water ranged from 0.42 to 0.62 in tested formulations. The half-release (t 1/2 ) values ranged from 17.35 to 35.14 days, and the period of optimum availability of Mancozeb ranged from 18.54 to 35.42 days. Further, the in vitro bioefficacy evaluation of developed formulations was done against plant pathogenic fungi Alternaria solani and Sclerotium rolfsii by poison food technique. Effective dose for 50% inhibition in mgL -1 (ED 50 ) values of developed formulations varied from 1.31 to 2.79 mg L -1 for A. solani, and 1.60 to 3.14 mg L -1 for S. rolfsii. The present methodology is simple, economical, and eco-friendly for the development of environment-friendly CR formulations of Mancozeb. These formulations can be used to optimize the release of Mancozeb to achieve disease control for the desired period depending upon the matrix of the polymer used. Importantly, the maximum amount of active ingredient remains available for a reasonable period after application. In addition, the developed CR formulations were found to be suitable for fungicidal applications, allowing use of Mancozeb in lower doses.

Synthesis and characterization of mannosylated pegylated polyethylenimine as a carrier for siRNA

PubMed Central

Kim, NaJung; Jiang, Dahai; Jacobi, Ashley; Lennox, Kim A.; Rose, Scott; Behlke, Mark A.; Salem, Aliasger K.

2011-01-01

Regulation of gene expression using small interfering RNA (siRNA) is a promising strategy for research and treatment of numerous diseases. In this study, we develop and characterize a delivery system for siRNA composed of polyethylenimine (PEI), polyethylene glycol (PEG), and mannose (Man). Cationic PEI complexes and compacts siRNA, PEG forms a hydrophilic layer outside of the polyplex for steric stabilization, and mannose serves as a cell binding ligand for macrophages. The PEI-PEG-mannose delivery system was constructed in two different ways. In the first approach, mannose and PEG chains are directly conjugated to the PEI backbone. In the second approach, mannose is conjugated to one end of the PEG chain and the other end of the PEG chain is conjugated to the PEI backbone. The PEI-PEG-mannose delivery systems were synthesized with 3.45 – 13.3 PEG chains and 4.7 – 3.0 mannose molecules per PEI. The PEI-PEG-Man-siRNA polyplexes displayed a coarse surface in Scanning Electron Microscopy (SEM) images. Polyplex sizes were found to range from 169nm to 357nm. Gel retardation assays showed that the PEI-PEG-mannose polymers are able to efficiently complex with siRNA at low N/P ratios. Confocal microscope images showed that the PEI-PEG-Man-siRNA polyplexes could enter cells and localized in the lysosomes at 2 hours post-incubation. Pegylation of the PEI reduced toxicity without any adverse reduction in knockdown efficiency relative to PEI alone. Mannosylation of the PEI-PEG could be carried out without any significant reduction in knockdown efficiency relative to PEI alone. Conjugating mannose to PEI via the PEG spacer generated superior toxicity and gene knockdown activity relative to conjugating mannose and PEG directly onto the PEI backbone. PMID:21864664

Influence of different peg length in glenoid bone loss: A biomechanical analysis regarding primary stability of the glenoid baseplate in reverse shoulder arthroplasty.

PubMed

Königshausen, M; Jettkant, B; Sverdlova, N; Ehlert, C; Gessmann, J; Schildhauer, T A; Seybold, D

2015-01-01

There is no biomechanical basis to determine the influence of different length of the central peg of the baseplate anchored within the native scapula in glenoid defect reconstruction in cases of degenerative or posttraumatic glenoid bone loss in reversed shoulder arthroplasty. The purpose of this study was to analyse the stability of different peg lengths used in glenoid bone loss in reversed shoulder arthroplasty. Different lengths of metaglene pegs with different depths of peg anchorage performed with or without metaglene screws in sawbone foam blocks were loaded in vertical and horizontal directions for differentiating load capacities. Simulated physiological loadings were then applied to the peg implants to determine the limits of loading in each depth of anchorage. The loading capacity of the implant was reduced as less of the peg was anchored. The vertically loaded implants showed a significantly higher stability, in contrast to those loaded horizontally at a corresponding peg length and depth of anchorage (p < 0.05). The tests revealed that the metaglene screws are more essential for primary stability than is the peg particularly in the vertically directed loadings (2/3 anchored: peg contributed to 28% of the stability, 1/3 anchorage: peg contributed to 12%). Under the second test conditions, the lowest depth of peg anchorage (1/3) resulted in 322 Newtons [N] in the long peg with a vertical loading direction, and in 130 N in the long peg with a horizontal loading direction (p < 0.05). The pegs should be anchored as deeply as possible into the native scapula bone stock. The metaglene screws play a major role in the initial stability, in contrast to the peg, and they become more important when the depth of the peg anchorage is reduced. If possible, four metaglene screws should be used in cases of uncontained bone loss to guarantee the highest stability.

Encapsulation, controlled release, and antitumor efficacy of cisplatin delivered in liposomes composed of sterol-modified phospholipids

DOE PAGES

Kieler-Ferguson, Heidi M.; Chan, Darren; Sockolosky, Jonathan; ...

2017-03-03

Here, we employed a recently introduced class of sterol-modified lipids (SML) to produce m-PEG-DSPE containing liposome compositions with a range of cis-platinum content release rates. SML have a cholesterol succinate attached to the phosphatidylglycerol head group and a fatty acid at the 2 position. These compositions were compared to the well-studied liposome phospholipid compositions: mPEG-DSPE/Hydrogenated Soy PC/cholesterol or mPEG-DSPE/POPC/cholesterol to determine the effect of the cis-platinum release extent on C26 tumor proliferation in the BALB/c colon carcinoma mouse model. The release rates of cis-platinum from liposomes composed of SML are a function of the acyl chain length. SML-liposomes with shortermore » acyl chain lengths C-8 provided more rapid cisplatin release, lower in vitro IC50, and were easier to formulate compared to liposomes using traditional phospholipid compositions. Similar to other liposome cis-platinum formulations, the half-life of m-PEG-DSPE SML liposome cisplatin is substantially longer than the free drug. This resulted in a higher tumor cisplatin concentration at 48 h post-dosing compared to the free drug and higher Pt-DNA adducts in the tumor. Moreover, the maximum tolerated dose of the liposome formulations where up to four fold greater than the free drug. Using X-ray fluorescence spectroscopy on tumor sections, we compared the location of platinum, to the location of a fluorescence lipid incorporated in the liposomes. The liposome platinum co-localized with the fluorescent lipid and both were non-uniformly distributed in the tumor. Non-encapsulated Cis-platinum, albeit at a low concentration, was more uniformly distributed thorough the tumor. Three liposome formulations, including the well studied hydrogenated HSPC composition, had better antitumor activity in the murine colon 26 carcinoma model as compared to the free drug at the same dose but the SML liposome platinum formulations did not perform better than the HSPC formulation.« less

Encapsulation, controlled release, and antitumor efficacy of cisplatin delivered in liposomes composed of sterol-modified phospholipids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kieler-Ferguson, Heidi M.; Chan, Darren; Sockolosky, Jonathan

Here, we employed a recently introduced class of sterol-modified lipids (SML) to produce m-PEG-DSPE containing liposome compositions with a range of cis-platinum content release rates. SML have a cholesterol succinate attached to the phosphatidylglycerol head group and a fatty acid at the 2 position. These compositions were compared to the well-studied liposome phospholipid compositions: mPEG-DSPE/Hydrogenated Soy PC/cholesterol or mPEG-DSPE/POPC/cholesterol to determine the effect of the cis-platinum release extent on C26 tumor proliferation in the BALB/c colon carcinoma mouse model. The release rates of cis-platinum from liposomes composed of SML are a function of the acyl chain length. SML-liposomes with shortermore » acyl chain lengths C-8 provided more rapid cisplatin release, lower in vitro IC50, and were easier to formulate compared to liposomes using traditional phospholipid compositions. Similar to other liposome cis-platinum formulations, the half-life of m-PEG-DSPE SML liposome cisplatin is substantially longer than the free drug. This resulted in a higher tumor cisplatin concentration at 48 h post-dosing compared to the free drug and higher Pt-DNA adducts in the tumor. Moreover, the maximum tolerated dose of the liposome formulations where up to four fold greater than the free drug. Using X-ray fluorescence spectroscopy on tumor sections, we compared the location of platinum, to the location of a fluorescence lipid incorporated in the liposomes. The liposome platinum co-localized with the fluorescent lipid and both were non-uniformly distributed in the tumor. Non-encapsulated Cis-platinum, albeit at a low concentration, was more uniformly distributed thorough the tumor. Three liposome formulations, including the well studied hydrogenated HSPC composition, had better antitumor activity in the murine colon 26 carcinoma model as compared to the free drug at the same dose but the SML liposome platinum formulations did not perform better than the HSPC formulation.« less

Crystalline and dynamic mechanical behaviors of synthesized poly(sebacic anhydride-co-ethylene glycol).

PubMed

Chan, Cheng-Kuang; Chu, I-Ming

2003-01-01

A novel biomaterial: poly(sebacic anhydride-co-ethylene glycol) was synthesized by introducing poly(ethylene glycol) (PEG) into a polyanhydride system. This copolymer was synthesized using sebacic acid and PEG via melt-condensation polymerization. The crystalline behavior of these synthesized products was studied, and compared to that of polymer blends of poly(sebacic anhydride) (PSA) and PEG. The crystallinity of PSA chain segments can be significantly enhanced by increasing chain mobility via the introduction of PEG. The crystallinity of the PSA component in copolymers was substantially greater than that of blends. However, the crystalline growth of the PEG segments was totally hindered by the presence of PSA chain segments, such that no crystal for PEG component was found in these copolymers. Besides, a dynamic mechanical analysis of these materials was also performed to provide additional information concerning visco-elastic behavior for other biomedical applications, where it was found that the viscous behavior in copolymers was more significant than in neat PSA and PEG. Copyright 2002 Elsevier Science Ltd.

Tunable Surface Repellency Maintains Stemness and Redox Capacity of Human Mesenchymal Stem Cells.

PubMed

Balikov, Daniel A; Crowder, Spencer W; Boire, Timothy C; Lee, Jung Bok; Gupta, Mukesh K; Fenix, Aidan M; Lewis, Holley N; Ambrose, Caitlyn M; Short, Philip A; Kim, Chang Soo; Burnette, Dylan T; Reilly, Matthew A; Murthy, N Sanjeeva; Kang, Mi-Lan; Kim, Won Shik; Sung, Hak-Joon

2017-07-12

Human bone marrow derived mesenchymal stem cells (hMSCs) hold great promise for regenerative medicine due to their multipotent differentiation capacity and immunomodulatory capabilities. Substantial research has elucidated mechanisms by which extracellular cues regulate hMSC fate decisions, but considerably less work has addressed how material properties can be leveraged to maintain undifferentiated stem cells. Here, we show that synthetic culture substrates designed to exhibit moderate cell-repellency promote high stemness and low oxidative stress-two indicators of naïve, healthy stem cells-in commercial and patient-derived hMSCs. Furthermore, the material-mediated effect on cell behavior can be tuned by altering the molar percentage (mol %) and/or chain length of poly(ethylene glycol) (PEG), the repellant block linked to hydrophobic poly(ε-caprolactone) (PCL) in the copolymer backbone. Nano- and angstrom-scale characterization of the cell-material interface reveals that PEG interrupts the adhesive PCL domains in a chain-length-dependent manner; this prevents hMSCs from forming mature focal adhesions and subsequently promotes cell-cell adhesions that require connexin-43. This study is the first to demonstrate that intrinsic properties of synthetic materials can be tuned to regulate the stemness and redox capacity of hMSCs and provides new insight for designing highly scalable, programmable culture platforms for clinical translation.

In situ crosslinking of surface-initiated ring opening metathesis polymerization of polynorbornene for improved stability.

PubMed

Fursule, Ishan A; Abtahi, Ashkan; Watkins, Charles B; Graham, Kenneth R; Berron, Brad J

2018-01-15

In situ crosslinking is expected to increase the solvent stability of coatings formed by surface-initiated ring opening metathesis polymerization (SI ROMP). Solvent-associated degradation limits the utility of SI ROMP coatings. SI ROMP coatings have a unique capacity for post-functionalization through reaction of the unsaturated site on the polymer backbone. Any post-reaction scheme which requires a liquid solvent has the potential to degrade the coating and lower the thickness of the resulting film. We designed a macromolecular crosslinking group based on PEG dinorbornene. The PEG length is tailored to the expected mean chain to chain distance during surface-initiated polymerization. This crosslinking macromer is randomly copolymerized with norbornene through SI ROMP on a gold coated substrate. The solvent stability of polynorbornene coatings with and without PEG dinorbornene is quantitatively determined, and the mechanism of degradation is further supported through XPS and AFM analyses. The addition of the 0.25mol% PEG dinorbornene significantly increases the solvent stability of the SI ROMP coatings. The crosslinker presence in the more stable films is supported with observable PEG absorbances by FTIR and an increase in contact angle hysteresis when compared to non-crosslinked coatings. The oxidation of the SI ROMP coatings is supported by the observation of carbonyl oxygen in the polynorbornene coatings. The rapid loss of the non-crosslinked SI ROMP coating corresponds to nanoscale pitting across the surface and micron-scale regions of widespread film loss. The crosslinked coatings have uniform nanoscale pitting, but the crosslinked films show no evidence of micron-scale film damage. In all, the incorporation of minimal crosslinking content is a simple strategy for improving the solvent stability of SI ROMP coatings. Copyright © 2017 Elsevier Inc. All rights reserved.

Amphiphilic graft polymer with reduction breakable main chain prepared via click polymerization and grafting onto

NASA Astrophysics Data System (ADS)

Zhang, Xiaojin; Dai, Yu

2018-06-01

Amphiphilic graft polymer PSS- g-Pal/PEG with reduction breakable main chain was synthesized via click polymerization of dialkynyl (containing disulfide bond) and diazide (containing pendant diol) and one-pot grafting onto of hydrophobic palmitate (Pal) and hydrophilic methoxy poly(ethylene glycol) (PEG). PSS- g-Pal/PEG is able to form polymeric micelles by self-assembly in water via dialysis. Polymeric micelles are nano-sized spheres and the particle size is approximately 70 nm. Of note, polymeric micelles are reduction-responsive owing to the disulfide bonds in main chain of PSS- g-Pal/PEG. Therefore, polymeric micelles prepared from amphiphilic graft polymer PSS- g-Pal/PEG are able to fast release the drugs in the presence of the reducing agents such as DL-dithiothreitol (DTT).

Self-assembly behavior of a linear-star supramolecular amphiphile based on host-guest complexation.

PubMed

Wang, Juan; Wang, Xing; Yang, Fei; Shen, Hong; You, Yezi; Wu, Decheng

2014-11-04

A star polymer, β-cyclodextrin-poly(l-lactide) (β-CD-PLLA), and a linear polymer, azobenzene-poly(ethylene glycol) (Azo-PEG), could self-assemble into a supramolecular amphiphilic copolymer (β-CD-PLLA@Azo-PEG) based on the host-guest interaction between β-CD and azobenzene moieties. This linear-star supramolecular amphiphilic copolymer further self-assembled into a variety of morphologies, including sphere-like micelle, carambola-like micelle, naan-like micelle, shuttle-like lamellae, tube-like fiber, and random curled-up lamellae, by tuning the length of hydrophilic or hydrophobic chains. The variation of morphology was closely related to the topological structure and block ratio of the supramolecular amphiphiles. These self-assembly structures could disassemble upon an ultraviolet (UV) light irradiation.

A polymeric prodrug of 5-fluorouracil-1-acetic acid using a multi-hydroxyl polyethylene glycol derivative as the drug carrier.

PubMed

Li, Man; Liang, Zhen; Sun, Xun; Gong, Tao; Zhang, Zhirong

2014-01-01

Macromolecular prodrugs obtained by covalently conjugating small molecular drugs with polymeric carriers were proven to accomplish controlled and sustained release of the therapeutic agents in vitro and in vivo. Polyethylene glycol (PEG) has been extensively used due to its low toxicity, low immunogenicity and high biocompatibility. However, for linear PEG macromolecules, the number of available hydroxyl groups for drug coupling does not change with the length of polymeric chain, which limits the application of PEG for drug conjugation purposes. To increase the drug loading and prolong the retention time of 5-fluorouracil (5-Fu), a macromolecular prodrug of 5-Fu, 5-fluorouracil-1 acid-PAE derivative (5-FA-PAE) was synthesized and tested for the antitumor activity in vivo. PEG with a molecular weight of 38 kDa was selected to synthesize the multi-hydroxyl polyethylene glycol derivative (PAE) through an addition reaction. 5-fluorouracil-1 acetic acid (5-FA), a 5-Fu derivative was coupled with PEG derivatives via ester bond to form a macromolecular prodrug, 5-FA-PAE. The in vitro drug release, pharmacokinetics, in vivo distribution and antitumor effect of the prodrug were investigated, respectively. The PEG-based prodrug obtained in this study possessed an exceedingly high 5-FA loading efficiency of 10.58%, much higher than the maximum drug loading efficiency of unmodified PEG with the same molecular weight, which was 0.98% theoretically. Furthermore, 5-FA-PAE exhibited suitable sustained release in tumors. This study provides a new approach for the development of the delivery to tumors of anticancer agents with PEG derivatives.

Decorin causes autophagy in endothelial cells via Peg3

PubMed Central

Buraschi, Simone; Neill, Thomas; Goyal, Atul; Poluzzi, Chiara; Smythies, James; Owens, Rick T.; Schaefer, Liliana; Torres, Annabel; Iozzo, Renato V.

2013-01-01

Soluble decorin affects the biology of several receptor tyrosine kinases by triggering receptor internalization and degradation. We found that decorin induced paternally expressed gene 3 (Peg3), an imprinted tumor suppressor gene, and that Peg3 relocated into autophagosomes labeled by Beclin 1 and microtubule-associated light chain 3. Decorin evoked Peg3-dependent autophagy in both microvascular and macrovascular endothelial cells leading to suppression of angiogenesis. Peg3 coimmunoprecipitated with Beclin 1 and LC3 and was required for maintaining basal levels of Beclin 1. Decorin, via Peg3, induced transcription of Beclin 1 and microtubule-associated protein 1 light chain 3 alpha genes, thereby leading to a protracted autophagic program. Mechanistically, decorin interacted with VEGF receptor 2 (VEGFR2) in a region overlapping with its natural ligand VEGFA, and VEGFR2 was required for decorin-evoked Beclin 1 and microtubule-associated protein 1 light chain 3 alpha expression as well as for Peg3 induction in endothelial cells. Moreover, decorin induced VEGFR2-dependent mitochondrial fragmentation and loss of mitochondrial membrane potential. Thus, we have unveiled a mechanism for a secreted proteoglycan in inducing Peg3, a master regulator of macroautophagy in endothelial cells. PMID:23798385

Fluorescent water-Soluble Probes Based on Ammonium Cation Peg Substituted Perylenepisimides: Synthesis, Photophysical Properties, and Live Cell Images

NASA Astrophysics Data System (ADS)

Yang, Wei; Cai, Jiaxuan; Zhang, Shuchen; Yi, Xuegang; Gao, Baoxiang

2018-01-01

To synthesize perylenbisimides (PBI) fluorescent probes that will improve the water-soluble ability and the cytocompatibility, the synthesis and properties of fluorescent water-soluble probes based on dendritic ammonium cation polyethylene glycol (PEG) substituted perylenebisimides(GPDIs) are presented. As we expected, with increased ammonium cation PEG, the aggregation of the PBI in an aqueous solution is completely suppressed by the hydrophilic ammonium cation PEG groups. And the fluorescence quantum yield increases from 25% for GPDI-1 to 62% for GPDI-2. When incubated with Hela cells for 48 h, the viabilities are 71% (for GPDI-1) and 76% (for GPDI-2). Live cell imaging shows that these probes are efficiently internalized by HeLa cells. The study of the photophysical properties indicated increasing the ammonium cation PEG generation can increase the fluorescence quantum yield. Live cell imaging shows that with the ammonium cation PEG chains of perylenebisimides has high biocompatibility. The exceptionally low cytotoxicity is ascribed to the ammonium cation PEG chains, which protect the dyes from nonspecifically interacting with the extracellular proteins. Live cell imaging shows that ammonium cations PEG chains can promote the internalization of these probes.

Solubility and binding properties of PEGylated lysozyme derivatives with increasing molecular weight on hydrophobic-interaction chromatographic resins.

PubMed

Müller, Egbert; Josic, Djuro; Schröder, Tim; Moosmann, Anna

2010-07-09

Dynamic binding capacities and resolution of PEGylated lysozyme derivatives with varying molecular weights of poly (ethylene) glycol (PEG) with 5 kDa, 10 kDa and 30 kDa for HIC resins and columns are presented. To find the optimal range for the operating conditions, solubility studies were performed by high-throughput analyses in a 96-well plate format, and optimal salt concentrations and pH values were determined. The solubility of PEG-proteins was strongly influenced by the length of the PEG moiety. Large differences in the solubilities of PEGylated lysozymes in two different salts, ammonium sulfate and sodium chloride were found. Solubility of PEGylated lysozyme derivatives in ammonium sulfate decreases with increased length of attached PEG chains. In sodium chloride all PEGylated lysozyme derivatives are fully soluble in a concentration range between 0.1 mg protein/ml and 10 mg protein/ml. The binding capacities for PEGylated lysozyme to HIC resins are dependent on the salt type and molecular weight of the PEG polymer. In both salt solutions, ammonium sulfate and sodium chloride, the highest binding capacity of the resin was found for 5 kDa PEGylated lysozyme. For both native lysozyme and 30 kDa mono-PEGylated lysozyme the binding capacities were lower. In separation experiments on a TSKgel Butyl-NPR hydrophobic-interaction column with ammonium sulfate as mobile phase, the elution order was: native lysozyme, 5 kDa mono-PEGylated lysozyme and oligo-PEGylated lysozyme. This elution order was found to be reversed when sodium chloride was used. Furthermore, the resolution of the three mono-PEGylated forms was not possible with this column and ammonium sulfate as mobile phase. In 4 M sodium chloride a resolution of all PEGylated lysozyme forms was achieved. A tentative explanation for these phenomena can be the increased solvation of the PEG polymers in sodium chloride which changes the usual attractive hydrophobic forces in ammonium sulfate to more repulsive hydration forces in this hydrotrophic salt.

Design of polymer conjugated 3-helix micelles as nanocarriers with tunable shapes.

PubMed

Ma, Dan; DeBenedictis, Elizabeth P; Lund, Reidar; Keten, Sinan

2016-11-24

Amphiphilic peptide-polymer conjugates have the ability to form stable nanoscale micelles, which show great promise for drug delivery and other applications. A recent design has utilized the end-conjugation of alkyl chains to 3-helix coiled coils to achieve amphiphilicity, combined with the side-chain conjugation of polyethylene glycol (PEG) to tune micelle size through entropic confinement forces. Here we investigate this phenomenon in depth, using coarse-grained dissipative particle dynamics (DPD) simulations in an explicit solvent and micelle theory. We analyze the conformations of PEG chains conjugated to three different positions on 3-helix bundle peptides to ascertain the degree of confinement upon assembly, as well as the ordering of the subunits making up the micelle. We discover that the micelle size and stability is dictated by a competition between the entropy of PEG chain conformations in the assembled state, as well as intermolecular cross-interactions among PEG chains that promote cohesion between neighboring conjugates. Our analyses build on the role of PEG molecular weight and conjugation site and lead to computational phase diagrams that can be used to design 3-helix micelles. This work opens pathways for the design of multifunctional micelles with tunable size, shape and stability.

Rationally designed dual functional block copolymers for bottlebrush-like coatings: In vitro and in vivo antimicrobial, antibiofilm, and antifouling properties.

PubMed

Gao, Qiang; Yu, Meng; Su, Yajuan; Xie, Meihua; Zhao, Xin; Li, Peng; Ma, Peter X

2017-03-15

Numerous antimicrobial coatings have been developed for biomedical devices/implants, but few can simultaneously fulfill the requirements for antimicrobial and antifouling ability and biocompatibility. In this study, to develop an antimicrobial and antibiofilm surface coating, diblock amphiphilic molecules with antimicrobial and antifouling segments in a single chain were rationally designed and synthesized. Cationic antimicrobial polypeptides (AMP) were first synthesized by N-carboxyanhydride ring-opening polymerization (NCA-ROP). Heterofunctionalized poly(ethylene glycol) with different lengths (methacrylate-PEG n -tosyl, n=10/45/90) was synthesized and site-specifically conjugated with polypeptides to form diblock amphiphiles. Along with increased PEG chain length, hemolytic activity was considerably improved, and broad-spectrum antimicrobial activity is retained. Three MA-PEG n -b-AMP copolymers were further grafted onto the surface of silicone rubber (a commonly used catheter material) via plasma/UV-induced surface polymerizations to form a bottlebrush-like coating with excellent antimicrobial activity against several pathogenic bacteria (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus), and effectively prevent biofilm formation. This bottlebrush coating also greatly reduced protein adsorption and platelet adhesion, indicating its excellent antifouling ability. An in vitro cytotoxicity study also demonstrated that this coating is biocompatible with mammalian cells. After subcutaneous implantation of the materials in rats, we demonstrated that the g-PEG 45 -b-AMP bottlebrush coating exhibits significant anti-infective activity in vivo. Thus, this facilely synthesized PEGylated AMP bottlebrush coating is a feasible method to prevent biomedical devices-associated infections. Current antimicrobial coatings are often associated with concerns such as antibiotic resistance, environmental pollution, short-time antimicrobial activity, biofouling, poor blood compatibility and cytotoxicity, etc. To overcome these drawbacks, a robust PEGylated cationic amphiphilic peptides-based bottlebrush-like surface coating is demonstrated here, which fulfil the requirements of antimicrobial and antifouling as well as biocompatibility in the meantime. Briefly, the rational designed g-PEG n -b-AMP block copolymers (n=10/45/90) were synthesized and grafted on silicone surface. This bottlebrush-like coating efficiently kill the contacted bacteria and prevent the biofilm formation, greatly reduced protein and platelet adhesion. It also exhibits excellent blood compatibility and low cytotoxicity in vitro. In particular, g-PEG 45 -b-AMP coating exhibits significant anti-infection effect in vivo. This coating offering an effective strategy for combating biomedical devices-associated infections. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Mesoporous Akaganeite of Adjustable Pore Size Synthesized using Mixed Templates

NASA Astrophysics Data System (ADS)

Zhang, Y.; Ge, D. L.; Ren, H. P.; Fan, Y. J.; Wu, L. M.; Sun, Z. X.

2017-12-01

Mesoporous akaganeite with large and adjustable pore size was synthesized through a co-template method, which was achieved by the combined interaction between PEG2000 and alkyl amines with different lengths of the straight carbon chain. The characterized results indicate that the synthesized samples show comparatively narrow BJH pore size distributions and centered at 14.3 nm when PEG and HEPA was used, and it could be enlarged to 16.8 and 19.4 nm respectively through changing the alkyl amines to DDA and HDA. Meanwhile, all the synthesized akaganeite possess relativity high specific surface area ranging from 183 to 281 m2/g and high total pore volume of 0.98 to 1.5 cm3/g. A possible mechanism leading to the pore size changing was also proposed.

Controlled Self-Assembly of Cyclophane Amphiphiles: From 1D Nanofibers to Ultrathin 2D Topological Structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cai, Zhengxu; Li, Lianwei; Lo, Wai-Yip

2016-07-05

A novel series of amphiphilic TC-PEG molecules were designed and synthesized based on the orthogonal cyclophane unit. These molecules were able to self-assemble from 1D nanofibers and nanobelts to 2D ultrathin nanosheets (3 nm thick) in a controlled way by tuning the length of PEG side chains. The special structure of the cyclophane moiety allowed control in construction of nanostructures through programmed noncovalent interactions (hydrophobic hydrophilic interaction and pi-pi interaction). The self-assembled nanostructures were characterized by combining real space imaging (TEM, SEM, and AFM) and reciprocal space scattering (GIWAXS) techniques. This unique supramolecular system may provide a new strategy formore » the design of materials with tunable nanomorphology and functionality.« less

Towards potential nanoparticle contrast agents: Synthesis of new functionalized PEG bisphosphonates.

PubMed

Kachbi-Khelfallah, Souad; Monteil, Maelle; Cortes-Clerget, Margery; Migianu-Griffoni, Evelyne; Pirat, Jean-Luc; Gager, Olivier; Deschamp, Julia; Lecouvey, Marc

2016-01-01

The use of nanotechnologies for biomedical applications took a real development during these last years. To allow an effective targeting for biomedical imaging applications, the adsorption of plasmatic proteins on the surface of nanoparticles must be prevented to reduce the hepatic capture and increase the plasmatic time life. In biologic media, metal oxide nanoparticles are not stable and must be coated by biocompatible organic ligands. The use of phosphonate ligands to modify the nanoparticle surface drew a lot of attention in the last years for the design of highly functional hybrid materials. Here, we report a methodology to synthesize bisphosphonates having functionalized PEG side chains with different lengths. The key step is a procedure developed in our laboratory to introduce the bisphosphonate from acyl chloride and tris(trimethylsilyl)phosphite in one step.

A Polymeric Prodrug of 5-Fluorouracil-1-Acetic Acid Using a Multi-Hydroxyl Polyethylene Glycol Derivative as the Drug Carrier

PubMed Central

Sun, Xun; Gong, Tao; Zhang, Zhirong

2014-01-01

Purpose Macromolecular prodrugs obtained by covalently conjugating small molecular drugs with polymeric carriers were proven to accomplish controlled and sustained release of the therapeutic agents in vitro and in vivo. Polyethylene glycol (PEG) has been extensively used due to its low toxicity, low immunogenicity and high biocompatibility. However, for linear PEG macromolecules, the number of available hydroxyl groups for drug coupling does not change with the length of polymeric chain, which limits the application of PEG for drug conjugation purposes. To increase the drug loading and prolong the retention time of 5-fluorouracil (5-Fu), a macromolecular prodrug of 5-Fu, 5-fluorouracil-1 acid-PAE derivative (5-FA-PAE) was synthesized and tested for the antitumor activity in vivo. Methods PEG with a molecular weight of 38 kDa was selected to synthesize the multi-hydroxyl polyethylene glycol derivative (PAE) through an addition reaction. 5-fluorouracil-1 acetic acid (5-FA), a 5-Fu derivative was coupled with PEG derivatives via ester bond to form a macromolecular prodrug, 5-FA-PAE. The in vitro drug release, pharmacokinetics, in vivo distribution and antitumor effect of the prodrug were investigated, respectively. Results The PEG-based prodrug obtained in this study possessed an exceedingly high 5-FA loading efficiency of 10.58%, much higher than the maximum drug loading efficiency of unmodified PEG with the same molecular weight, which was 0.98% theoretically. Furthermore, 5-FA-PAE exhibited suitable sustained release in tumors. Conclusion This study provides a new approach for the development of the delivery to tumors of anticancer agents with PEG derivatives. PMID:25389968

Accelerated cell sheet detachment by copolymerizing hydrophilic PEG side chains into PNIPAm nanocomposite hydrogels.

PubMed

Liu, Dan; Wang, Tao; Liu, Xinxing; Tong, Zhen

2012-10-01

One-end-connected short poly(ethylene glycol) (PEG) side chains were facilely introduced into the poly(N-isopropylacrylamide) (PNIPAm) nanocomposite hydrogel (NC gel) via in situ copolymerization of NIPAm monomer and PEG macromonomer in the aqueous suspension of hectorite clay Laponite XLS. The NC gels were characterized with Fourier transform infrared and x-ray photoelectron spectroscopy for the composition, DSC and transmittance for the phase separation temperature, dynamic mechanical spectra and swelling ratio for the interaction. Increasing the PEG content led to a small increase in the storage modulus and the lower critical solution temperature (LCST) of the copolymerized NC gels, and the LCST of the copolymerized NC gels was still below 37 °C. The L929 cell adhesion and proliferation on the surface of these NC gels were not suppressed by the incorporation of hydrophilic PEG side chains. By lowering temperature below the LCST, the cell sheet spontaneously detached from the copolymerized NC gels. The surface morphology and surface wettability of the NC gels were detected by atom force microscope and contact angle measurement. A rough and hydrophilic surface induced by a small amount of PEG side chains was found to be favorable to accelerate the cell sheet detachment, probably due to the enhanced water permeation into the gel-cell sheet interface.

Sol-gel immobilized short-chain poly(ethylene glycol) coating for capillary microextraction of underivatized polar analytes.

PubMed

Kulkarni, Sameer; Shearrow, Anne M; Malik, Abdul

2007-12-07

Sol-gel coating with covalently bonded low-molecular-weight (MW<300 Da) poly(ethylene glycol) (PEG) chains was developed for capillary microextraction (CME). The sol-gel chemistry proved effective in the immobilization of low-molecular-weight PEGs thanks to the formation of chemical bonds between the organic-inorganic hybrid sol-gel PEG coating and the fused silica capillary inner surface. This chemical anchorage provided excellent thermal and solvent stability to the created sol-gel PEG coating as is evidenced by its high upper limit of allowable conditioning temperature (340 degrees C) and its practically identical performance before and after rinsing with various solvents. The prepared sol-gel PEG coating provided simultaneous extraction of moderately polar and highly polar analytes from aqueous samples without requiring derivatization, pH adjustment or salting-out procedures. Detection limits on the order of nanogram per liter (ng/L) were achieved in CME-GC-flame ionization detection experiments designed for the preconcentration and trace analysis of both highly polar and moderately polar compounds extracted directly from aqueous media using sol-gel short-chain PEG coated microextraction capillaries.

Block copolymer micelles with acid-labile ortho ester side-chains: Synthesis, characterization, and enhanced drug delivery to human glioma cells.

PubMed

Tang, Rupei; Ji, Weihang; Panus, David; Palumbo, R Noelle; Wang, Chun

2011-04-10

A new type of block copolymer micelles for pH-triggered delivery of poorly water-soluble anticancer drugs has been synthesized and characterized. The micelles were formed by the self-assembly of an amphiphilic diblock copolymer consisting of a hydrophilic poly(ethylene glycol) (PEG) block and a hydrophobic polymethacrylate block (PEYM) bearing acid-labile ortho ester side-chains. The diblock copolymer was synthesized by atom transfer radical polymerization (ATRP) from a PEG macro-initiator to obtain well-defined polymer chain-length. The PEG-b-PEYM micelles assumed a stable core-shell structure in aqueous buffer at physiological pH with a low critical micelle concentration as determined by proton NMR and pyrene fluorescence spectroscopy. The hydrolysis of the ortho ester side-chain at physiological pH was minimal yet much accelerated at mildly acidic pHs. Doxorubicin (Dox) was successfully loaded into the micelles at pH 7.4 and was released at a much higher rate in response to slight acidification to pH 5. Interestingly, the release of Dox at pH 5 followed apparently a biphasic profile, consisting of an initial fast phase of several hours followed by a sustained release period of several days. Dox loaded in the micelles was rapidly taken up by human glioma (T98G) cells in vitro, accumulating in the endolysosome and subsequently in the nucleus in a few hours, in contrast to the very low uptake of free drug at the same dose. The dose-dependent cytotoxicity of the Dox-loaded micelles was determined by the MTT assay and compared with that of the free Dox. While the empty micelles themselves were not toxic, the IC(50) values of the Dox-loaded micelles were approximately ten-times (by 24h) and three-times (by 48h) lower than the free drug. The much enhanced potency in killing the multi-drug-resistant human glioma cells by Dox loaded in the micelles could be attributed to high intracellular drug concentration and the subsequent pH-triggered drug release. These results establish the PEG-b-PEYM block copolymer with acid-labile ortho ester side-chains as a novel and effective pH-responsive nano-carrier for enhancing the delivery of drugs to cancer cells. Copyright © 2010 Elsevier B.V. All rights reserved.

PEGylation of polylysine dendrimers improves absorption and lymphatic targeting following SC administration in rats.

PubMed

Kaminskas, Lisa M; Kota, Jagannath; McLeod, Victoria M; Kelly, Brian D; Karellas, Peter; Porter, Christopher Jh

2009-12-03

Polylysine dendrimers have potential as highly flexible, biodegradable nanoparticular carriers that may also promote lymphatic transport. The current study was undertaken to determine the impact of PEGylation on the absorption and lymphatic transport of polylysine dendrimers modified by surface derivatisation with PEG (200, 570 or 2000Da) or 4-benzene sulphonate following SC or IV dosing. PEGylation led to the PEG(200) derived dendrimer being rapidly and completely absorbed into the blood after SC administration, however only 3% of the administered dose was recovered in pooled thoracic lymph over 30h. Increasing the PEG chain length led to a systematic decrease in absorption into the blood and an enhancement of the proportion recovered in the lymphatics (up to 29% over 30h). For the PEG(570) and PEG(2000) derived dendrimers, indirect access to the lymph via equilibration across the capillary beds also appeared to play a role in lymphatic targeting after both IV and SC dosing. In contrast, the anionic benzene sulphonate-capped dendrimer was not well absorbed from the SC injection site (26% bioavailability) into either the blood or the lymph. The data suggest that PEGylated poly-L-lysine dendrimers are well absorbed from SC injection sites and that the extent of lymphatic transport may be enhanced by increasing the size of the PEGylated dendrimer complex.

Preparation, characterization, and application of poly(vinyl alcohol)-graft-poly(ethylene glycol) resins: novel polymer matrices for solid-phase synthesis.

PubMed

Luo, Juntao; Pardin, Christophe; Zhu, X X; Lubell, William D

2007-01-01

Spherical crosslinked poly(vinyl alcohol) (PVA) beads with good mechanical stability were prepared by reverse-suspension polymerization, using dimethyl sulfoxide (DMSO) as a cosolvent in an aqueous phase. Poly(ethylene glycol)s with varying chain lengths were grafted onto the PVA beads by anionic polymerization of ethylene oxide. The thermal behavior, morphology, and swelling were evaluated for each of the new polymer matrices. High loading and good swelling in water and organic solvents were characteristic of the PEG-grafted PVA beads. The polymer beads also exhibited good mechanical and chemical stability and were unaffected by treatment with 6 N HCl and with 6 N NaOH. The hydroxyl groups of the PVA-PEG beads were converted into aldehyde, carboxylic acid, and isocyanate functions to provide scavenger resins and were extended by way of a benzyl alcohol in a Wang linker. The transglutaminase substrates dipeptides (Z-Gln-Gly) and heptapeptides (Pro-Asn-Pro-Gln-Leu-Pro-Phe) were synthesized on PVA-PEG_5, PVA-PEG_20, and the Wang linker-derivatized PVA-PEG resins. The cleavage of the peptides from the resins using MeOH/NH3 mixture at different temperatures (0 degrees C and room temp) and 50% TFA/DCM provided, respectively, peptide methyl esters, amides, and acids in good yields and purity as assessed by LC-MS analysis.

Acoustic, Thermal and Molecular Interactions of Polyethylene Glycol (2000, 3000, 6000)

NASA Astrophysics Data System (ADS)

Venkatramanan, K.; Padmanaban, R.; Arumugam, V.

Polyethylene Glycol (PEG) is a condensation polymer of ethylene oxide and water. PEG find its application as emulsifying agents, detergents, soaps, plasticizers, ointments, etc. Though the chemical and physical properties of PEG are known, still because of their uses in day to day life, it becomes necessary to study few physical properties like ultrasonic velocity, viscosity and hence adiabatic compressibility, free length, etc. In the present study, an attempt has been made to compute the activation energy and hence to analyse the molecular interactions of aqueous solutions of Polyethylene Glycol of molar mass 2000, 3000 and 6000 at different concentrations (2%, 4%, 6%, 8% and 10%) at different temperatures (303K, 308K, 313K, 318K) by determining relative viscosity, ultrasonic velocity and density. Various parameters like adiabatic compressibility, viscous relaxation time, inter molecular free length, free volume, internal pressure, etc are calculated at 303K and the results are discussed in the light of polymer-solvent interaction. This study helps to understand the behavior of macro-molecules with respect to changing concentration and temperature. Furthermore, viscosity and activation energy results are correlated to understand the increased entanglement of the polymer chains due to the increase in the concentration of a polymer solution that leads to an increase in viscosity and an increase in the activation energy of viscous flow.

Self-aggregation of cationically modified poly(ε-caprolactone)2-co-poly(ethylene glycol) copolymers: Effect of cationic grafting ligand and poly(ε-caprolactone) chain length.

PubMed

Charoongchit, Pimchanok; Suksiriworapong, Jiraphong; Sripha, Kittisak; Mao, Shirui; Sapin-Minet, Anne; Maincent, Philippe; Junyaprasert, Varaporn Buraphacheep

2017-03-01

Cationic copolymers have been attractive to investigate due to their potential to complexation with anionic drugs and expected to use in the pharmaceutical application. In this study, the modified poly(ε-caprolactone) 2 -co-poly(ethylene glycol) copolymers (P(CL) 2 -PEG) were successfully synthesized by click reaction. The amount of small molecular cationic ligand, propargyltrimethyl ammonium iodide, was varied and grafted onto various mole ratios of P(CL) to PEG. The effects of P(CL) chain length and amount of the grafting cationic ligand on physicochemical properties of polymers and particles were studied. The number-average molecular weights of the copolymers grafted with cationic ligand were found ranging between 10,000 and 23,000g/mol as investigated by NMR. From DSC study, the results showed that the grafting ligand affected thermal behaviors of the copolymers by increasing the glass transition temperature and decreasing the melting temperature of the copolymers. Furthermore, these cationic copolymers could self-aggregate with their critical aggregation concentration depending on mole ratios of hydrophilic to hydrophobic portions. The particles containing higher amounts of the cationic ligand tended to aggregate in both acidic and basic pH environment and at high salt concentration. Additionally, particle size, size distribution (PdI), and morphology of self-assembling particles varied depending on P(CL) chain length and the amount of the grafting cationic ligand. The synthesized cationic copolymer showed a capability to encapsulate a high negatively charged drug, enoxaparin, with an encapsulation efficiency of 87%. After drug incorporation, the particles substantially changed in size, shape, PdI, and zeta potential to become more suitable for drug delivery. These cationic copolymers with flexible properties will be the candidate for further development as carriers for the delivery of negatively charged drugs. Copyright © 2016. Published by Elsevier B.V.

Chemical modification of protein a chromatography ligands with polyethylene glycol. II: Effects on resin robustness and process selectivity.

PubMed

Weinberg, Justin; Zhang, Shaojie; Kirkby, Allison; Shachar, Enosh; Carta, Giorgio; Przybycien, Todd

2018-04-20

We have proposed chemical modification of Protein A (ProA) chromatography ligands with polyethylene glycol (PEGylation) as a strategy to increase the resin selectivity and robustness by providing the ligand with a steric repulsion barrier against non-specific binding. Here, we report on robustness and selectivity benefits for Repligen CaptivA PriMAB resin with ligands modified with 5.2 kDa and 21.5 kDa PEG chains, respectively. PEGylation of ProA ligands allowed the resin to retain a higher percentage of static binding capacity relative to the unmodified resin upon digestion with chymotrypsin, a representative serine protease. The level of protection against digestion was independent of the PEG molecular weight or modification extent for the PEGylation chemistry used. Additionally, PEGylation of the ligands was found to decrease the level of non-specific binding of fluorescently labeled bovine serum albumin (BSA) aggregates to the surface of the resin particles as visualized via confocal laser scanning microscopy (CLSM). The level of aggregate binding decreased as the PEG molecular weight increased, but increasing the extent of modification with 5.2 kDa PEG chains had no effect. Further examination of resin particles via CLSM confirmed that the PEG chains on the modified ligands were capable of blocking the "hitchhiking" association of BSA, a mock contaminant, to an adsorbed mAb that is prone to BSA binding. Ligands modified with 21.5 kDa PEG chains were effective at blocking the association, while ligands modified with 5.2 kDa PEG chains were not. Finally, ligands with 21.5 kDa PEG chains increased the selectivity of the resin against host cell proteins (HCPs) produced by Chinese Hamster Ovary (CHO) cells by up to 37% during purification of a monoclonal antibody (mAb) from harvested cell culture fluid (HCCF) using a standard ProA chromatography protocol. The combined work suggests that PEGylating ProA chromatography media is a viable pathway for increasing both resin lifetime and host cell impurity clearance in downstream bioprocessing. Copyright © 2018 Elsevier B.V. All rights reserved.

Towards potential nanoparticle contrast agents: Synthesis of new functionalized PEG bisphosphonates

PubMed Central

Kachbi-Khelfallah, Souad; Monteil, Maelle; Cortes-Clerget, Margery; Migianu-Griffoni, Evelyne; Pirat, Jean-Luc; Gager, Olivier; Deschamp, Julia

2016-01-01

Summary The use of nanotechnologies for biomedical applications took a real development during these last years. To allow an effective targeting for biomedical imaging applications, the adsorption of plasmatic proteins on the surface of nanoparticles must be prevented to reduce the hepatic capture and increase the plasmatic time life. In biologic media, metal oxide nanoparticles are not stable and must be coated by biocompatible organic ligands. The use of phosphonate ligands to modify the nanoparticle surface drew a lot of attention in the last years for the design of highly functional hybrid materials. Here, we report a methodology to synthesize bisphosphonates having functionalized PEG side chains with different lengths. The key step is a procedure developed in our laboratory to introduce the bisphosphonate from acyl chloride and tris(trimethylsilyl)phosphite in one step. PMID:27559386

Exploring Segment Lengths on the Geoboard

ERIC Educational Resources Information Center

Ellis, Mark W.; Pagni, David

2008-01-01

Given a 5-peg by 5-peg geoboard, how many different lengths can be made by stretching a rubber band to form an oblique segment between any two pegs? This investigation requires students to make connections to the Pythagorean theorem, congruence, and combinations. With its use of visual representation and a range of mathematical ideas that can be…

Surface Mechanical and Rheological Behaviors of Biocompatible Poly((D,L-lactic acid-ran-glycolic acid)-block-ethylene glycol) (PLGA-PEG) and Poly((D,L-lactic acid-ran-glycolic acid-ran-ε-caprolactone)-block-ethylene glycol) (PLGACL-PEG) Block Copolymers at the Air-Water Interface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Hyun Chang; Lee, Hoyoung; Khetan, Jawahar

Air–water interfacial monolayers of poly((d,l-lactic acid-ran-glycolic acid)-block-ethylene glycol) (PLGA–PEG) exhibit an exponential increase in surface pressure under high monolayer compression. In order to understand the molecular origin of this behavior, a combined experimental and theoretical investigation (including surface pressure–area isotherm, X-ray reflectivity (XR) and interfacial rheological measurements, and a self-consistent field (SCF) theoretical analysis) was performed on air–water monolayers formed by a PLGA–PEG diblock copolymer and also by a nonglassy analogue of this diblock copolymer, poly((d,l-lactic acid-ran-glycolic acid-ran-caprolactone)-block-ethylene glycol) (PLGACL–PEG). The combined results of this study show that the two mechanisms, i.e., the glass transition of the collapsed PLGA filmmore » and the lateral repulsion of the PEG brush chains that occur simultaneously under lateral compression of the monolayer, are both responsible for the observed PLGA–PEG isotherm behavior. Upon cessation of compression, the high surface pressure of the PLGA–PEG monolayer typically relaxes over time with a stretched exponential decay, suggesting that in this diblock copolymer situation, the hydrophobic domain formed by the PLGA blocks undergoes glass transition in the high lateral compression state, analogously to the PLGA homopolymer monolayer. In the high PEG grafting density regime, the contribution of the PEG brush chains to the high monolayer surface pressure is significantly lower than what is predicted by the SCF model because of the many-body attraction among PEG segments (referred to in the literature as the “n-cluster” effects). The end-grafted PEG chains were found to be protein resistant even under the influence of the “n-cluster” effects.« less

New sterically stabilized vesicles based on nonionic surfactant, cholesterol, and poly(ethylene glycol)-cholesterol conjugates.

PubMed Central

Beugin, S; Edwards, K; Karlsson, G; Ollivon, M; Lesieur, S

1998-01-01

Monomethoxypoly(ethylene glycol) cholesteryl carbonates (M-PEG-Chol) with polymer chain molecular weights of 1000 (M-PEG1000-Chol) and 2000 (M-PEG2000-Chol) have been newly synthesized and characterized. Their aggregation behavior in mixture with diglycerol hexadecyl ether (C16G2) and cholesterol has been examined by cryotransmission electron microscopy, high-performance gel exclusion chromatography, and quasielastic light scattering. Nonaggregated, stable, unilamellar vesicles were obtained at low polymer levels with optimal shape and size homogeneity at cholesteryl conjugate/ lipids ratios of 10 mol% M-PEG1000-Chol or 5 mol% M-PEG2000-Chol, corresponding to the theoretically predicted brush conformational state of the PEG chains. At 20 mol% M-PEG1000-Chol or 10 mol% M-PEG2000-Chol, the saturation threshold of the C16G2/cholesterol membrane in polymer is exceeded, and open disk-shaped aggregates are seen in coexistence with closed vesicles. Higher levels up to 30 mol% lead to the complete solubilization of the vesicles into disk-like structures of decreasing size with increasing PEG content. This study underlines the bivalent role of M-PEG-Chol derivatives: while behaving as solubilizing surfactants, they provide an efficient steric barrier, preventing the vesicles from aggregation and fusion over a period of at least 2 weeks. PMID:9635773

Impact of molecular weight and degree of conjugation on the thermodynamics of DNA complexation and stability of polyethylenimine-graft-poly(ethylene glycol) copolymers.

PubMed

Smith, Ryan J; Beck, Rachel W; Prevette, Lisa E

2015-01-01

Poly(ethylene glycol) (PEG) is often conjugated to polyethylenimine (PEI) to provide colloidal stability to PEI-DNA polyplexes and shield charge leading to toxicity. Here, a library of nine cationic copolymers was synthesized by grafting three molecular weights (750, 2000, 5000Da) of PEG to linear PEI at three conjugation ratios. Using isothermal titration calorimetry, we have quantified the thermodynamics of the associations between the copolymers and DNA and determined the extent to which binding is hindered as a function of PEG molecular weight and conjugation ratio. Low conjugation ratios of 750Da PEG to PEI resulted in little decrease in DNA affinity, but a significant decrease-up to two orders of magnitude-was found for the other copolymers. We identified limitations in determination of affinity using indirect assays (electrophoretic mobility shift and ethidium bromide exclusion) commonly used in the field. Dynamic light scattering of the DNA complexes at physiological ionic strength showed that PEI modifications that did not reduce DNA affinity also did not confer significant colloidal stability, a finding that was supported by calorimetric data on the aggregation process. These results quantify the DNA interaction thermodynamics of PEGylated polycations for the first time and indicate that there is an optimum PEG chain length and degree of substitution in the design of agents that have desirable properties for effective in vivo gene delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

Catalytic Mechanism of Short Ethoxy Chain Nonylphenol Dehydrogenase Belonging to a Polyethylene Glycol Dehydrogenase Group in the GMC Oxidoreductase Family

PubMed Central

Liu, Xin; Ohta, Takeshi; Kawabata, Takeshi; Kawai, Fusako

2013-01-01

Ethoxy (EO) chain nonylphenol dehydrogenase (NPEO-DH) from Ensifer sp. AS08 and EO chain octylphenol dehydrogenase from Pseudomonas putida share common molecular characteristics with polyethylene glycol (PEG) dehydrogenases (PEG-DH) and comprise a PEG-DH subgroup in the family of glucose-methanol-choline (GMC) oxidoreductases that includes glucose/alcohol oxidase and glucose/choline dehydrogenase. Three-dimensional (3D) molecular modeling suggested that differences in the size, secondary structure and hydropathy in the active site caused differences in their substrate specificities toward EO chain alkylphenols and free PEGs. Based on 3D molecular modeling, site-directed mutagenesis was utilized to introduce mutations into potential catalytic residues of NPEO-DH. From steady state and rapid kinetic characterization of wild type and mutant NPEO-DHs, we can conclude that His465 and Asn507 are directly involved in the catalysis. Asn507 mediates the transfer of proton from a substrate to FAD and His465 transfers the same proton from the reduced flavin to an electron acceptor. PMID:23306149

Catalytic mechanism of short ethoxy chain nonylphenol dehydrogenase belonging to a polyethylene glycol dehydrogenase group in the GMC oxidoreductase family.

PubMed

Liu, Xin; Ohta, Takeshi; Kawabata, Takeshi; Kawai, Fusako

2013-01-10

Ethoxy (EO) chain nonylphenol dehydrogenase (NPEO-DH) from Ensifer sp. AS08 and EO chain octylphenol dehydrogenase from Pseudomonas putida share common molecular characteristics with polyethylene glycol (PEG) dehydrogenases (PEG-DH) and comprise a PEG-DH subgroup in the family of glucose-methanol-choline (GMC) oxidoreductases that includes glucose/alcohol oxidase and glucose/choline dehydrogenase. Three-dimensional (3D) molecular modeling suggested that differences in the size, secondary structure and hydropathy in the active site caused differences in their substrate specificities toward EO chain alkylphenols and free PEGs. Based on 3D molecular modeling, site-directed mutagenesis was utilized to introduce mutations into potential catalytic residues of NPEO-DH. From steady state and rapid kinetic characterization of wild type and mutant NPEO-DHs, we can conclude that His465 and Asn507 are directly involved in the catalysis. Asn507 mediates the transfer of proton from a substrate to FAD and His465 transfers the same proton from the reduced flavin to an electron acceptor.

Single oral dose of cannabinoid derivate loaded PLGA nanocarriers relieves neuropathic pain for eleven days.

PubMed

Berrocoso, Esther; Rey-Brea, Raquel; Fernández-Arévalo, Mercedes; Micó, Juan Antonio; Martín-Banderas, Lucía

2017-11-01

Neuropathic pain, resistant to opiates and other drugs, is a chronic/persistent state with a complex treatment and often poor efficacy. In this scenario, cannabinoids are increasingly regarded as a genuine alternative. In this paper, and in an experimental animal model of neuropathic pain, we studied the efficacy of three kinds of PLGA nanoparticles containing synthetic cannabinoid CB13: (i) plain nanoparticles (PLGA); (ii) particles coated with PEG chains (PLGA+PEG) and (iii) particles possessing hydrophilic surfaces obtained by covalently binding PEG chains (PLGA-PEG). The optimized formulation, CB13-PLGA-PEG, showed high drug loading (13%) and small size (<300nm) with a narrow distribution and controlled surface properties (near-neutral zeta potential and stable PEG corona). Animal nociceptive behavioral studies were conducted by paw pressure and acetone tests. Versus the free CB13, CB13-PLGA-PEG nanoparticles showed a very noticeable analgesic efficacy with the longest sustained pain-relieving effect, lasting up to eleven days after one oral dose. Copyright © 2017 Elsevier Inc. All rights reserved.

Influence of polyethylene glycol on percolation dynamics of reverse microemulsions

NASA Astrophysics Data System (ADS)

Geethu, P. M.; Yadav, Indresh; Aswal, V. K.; Satapathy, D. K.

2018-04-01

We explore the influence of a hydrophilic polymer, polyethylene glycol (PEG), on the structure and the percolation dynamics of reverse microemulsions (ME) stabilized by an anionic surfactant AOT (sodium bis(2-ethylhexyl) sulfosuccinate). The percolation transition of MEs is probed using dielectric relaxation spectroscopy (DRS). Notably, an increase in percolation temperature is observed by the incorporation of PEG-polymer into larger ME droplets which is explained by considering the model of polymer adsorption at surfactant-water interface. The stability of the droplet phase of microemulsion after the incorporation of PEG is confirmed by small-angle neutron scattering (SANS) experiment. Further, a net decrease in percolation transition temperature is observed with the addition of PEG polymer for smaller ME droplets and is discussed in relation with the destabilization of droplets owing to the polymer induced bridging and the associated clustering of droplets. We conjecture that the adsorption of PEG polymer chains at the surfactant-water interface as well as the PEG-induced bridging of droplets are due to the strong ion-dipole interaction between anionic head group of AOT surfactant and dipoles present in PEG polymer chains.

The role of oxygen vacancies in resistive switching behavior of organic-TiO2 hybrid composite

NASA Astrophysics Data System (ADS)

Zhang, Jiahua; Chen, Da; Huang, Shihua

2017-10-01

Effects of polyethylene glycol (PEG) on resistive switching behaviors and mechanisms in organic-TiO2 hybrid composites were investigated. The reversed current-voltage curves in the negative bias during the initial voltage sweeps were first observed in the composites annealed at 150, 200 and 250 °C, which is ascribed to the accumulation of oxygen vacancies and the inhibition effect of polarities of PEG chains. In addition, the volatility of composites with relatively high content of PEG is caused by the inhibition effect of PEG on creating oxygen vacancies. The formation and rupture of oxygen-vacancy filaments was considered as the resistive switching mechanism. Finally, the charging and discharging process in PEG-TiO2 composite annealed at 150 °C results in the instability of the electron-occupied oxygen vacancies and the inhibition of PEG chains. This study demonstrates a new way to investigate the interaction between polymers and TiO2 for understanding the resistive switching mechanism of TiO2-based memories.

Lipolysis of the semi-solid self-emulsifying excipient Gelucire 44/14 by digestive lipases.

PubMed

Fernandez, Sylvie; Rodier, Jean-David; Ritter, Nicolas; Mahler, Bruno; Demarne, Frédéric; Carrière, Frédéric; Jannin, Vincent

2008-08-01

Gelucire 44/14 is a semi-solid self-emulsifying excipient used for the oral delivery of poorly water-soluble drugs. It is composed of C8-C18 acylglycerols and PEG-32 esters, all of which are potential substrates for digestive lipases. Here we studied the lipolysis of Gelucire 44/14 by porcine pancreatic extracts, human pancreatic juice and several purified digestive lipases. Human pancreatic lipase (HPL), the main lipase involved in the digestion of triacylglycerols, did not show any significant activity on Gelucire 44/14 or on either of its individual compounds, C8-C18 acylglycerols and PEG-32 esters. Other pancreatic lipases such as human pancreatic lipase-related protein 2 (HPLRP2) showed low activity on Gelucire 44/14 although the highest activity of HPLRP2 was that observed on the C8-C18 acylglycerol fraction, which accounts for 20% (w/w) of Gelucire 44/14. In addition, HPLRP2 showed low activities on the PEG-32 esters, whether these were tested individually or mixed together. Carboxyl ester hydrolase (CEH) showed high activity on Gelucire 44/14, and the highest activities of CEH were those recorded on the total PEG-32 ester fraction and on each individual PEG-32 ester, except for PEG-32 monostearate. The highest activity of all the enzymes tested was that of dog gastric lipase (DGL) on Gelucire 44/14, although DGL showed low activity on the PEG-32 ester fraction and on each individual PEG-32 ester. We compared the lipolysis of Gelucire 44/14 with that of Labrasol, another self-emulsifying excipient, which is liquid at room temperature. Human pancreatic juice showed similar rates of activity on both Gelucire 44/14 and Labrasol. This finding means that these excipients are hydrolyzed in vivo during pancreatic digestion, mainly by CEH in the case of Gelucire 44/14 and by both HPLRP2 and CEH in that of Labrasol, whereas HPL showed very low activities on each of these two excipients. This is the first time the effects of PEG and acyl chain length on the lipolytic activity of digestive lipases on PEG esters have been investigated.

Lipid and Lipid-Polymer Mixtures at an Interface

NASA Astrophysics Data System (ADS)

Kim, Joon Heon; Kim, Mahn Won

2000-03-01

The surface pressure (Π) and surface area/molecule (A) isotherms of a mixture of DMPC (DL-α-phosphatidylcholine,Dimyristoyl) and PEG-DMPE (1,2-Diacyl-sn-Glycero-3-Phosphoethanolamine-N-[Poly(ethylene glycol)5000]) system were measured at various compositions by the Langmuir surface balance technique at an air/water interface. In the range where the surface pressure is less than about 8 dynes/cm, a PEG polymer chain of PEG-DMPE molecules remains on the surface and the isotherm can be explained by the 2-D power law behavior of chains in a good solvent. In the range above 8 dynes/cm, a part of the PEG polymer segment is dissolved into the water phase, and the surface pressure can be explained as the sum of the 2-D component and 3-D component. Furthermore, the mixing energy is negative, which indicates an attractive interaction between DMPC and PEG-DMPE.

Lipid and lipid-polymer mixtures at an interface

NASA Astrophysics Data System (ADS)

Kim, Joon Heon; Kim, Mahn Won

2000-06-01

The surface pressure (Π) and surface area/molecule (A) isotherms of a mixture of DMPC (DL-α-phosphatidylcholine, Dimyristoyl) and PEG-DMPE (1,2-Diacyl-sn-Glycero-3-Phosphoethanolamine-N-[Poly(ethylene glycol)5000]) system were measured at various compositions by the Langmuir surface balance technique at an air/water interface. In the range where the surface pressure is less than about 8 dynes/cm, a PEG polymer chain of PEG-DMPE molecules remains on the surface and the isotherm can be explained by the 2-D power law behavior of chains in a good solvent. In the range above 8 dynes/cm, a part of the PEG polymer segment is dissolved into the water phase, and the surface pressure can be explained as the sum of the 2-D component and 3-D component. Furthermore, the mixing energy is negative, which indicates an attractive interaction between DMPC and PEG-DMPE. .

Comparison of biodegradation of poly(ethylene glycol)s and poly(propylene glycol)s.

PubMed

Zgoła-Grześkowiak, Agnieszka; Grześkowiak, Tomasz; Zembrzuska, Joanna; Łukaszewski, Zenon

2006-07-01

The biodegradation of poly(ethylene glycol)s (PEGs) and poly(propylene glycol)s (PPGs), both being major by-products of non-ionic surfactants biodegradation, was studied under the conditions of the River Water Die-Away Test. PEGs were isolated from a water matrix using solid-phase extraction with graphitized carbon black sorbent, then derivatized with phenyl isocyanate and determined by HPLC with UV detection. PPGs were isolated from a water matrix by liquid-liquid extraction with chloroform, then derivatized with naphthyl isocyanate and determined by HPLC with fluorescence detection. The primary biodegradation of both PEGs and PPGs reached approximately 99% during the test. The tests show different biodegradation pathways of PEG and PPG. During PEG biodegradation, their chains are shortened leading to the formation of ethylene glycol and diethylene glycol. During PPG biodegradation, no short-chained biodegradation products were found.

Conjugation of 10 kDa Linear PEG onto Trastuzumab Fab' Is Sufficient to Significantly Enhance Lymphatic Exposure while Preserving in Vitro Biological Activity.

PubMed

Chan, Linda J; Ascher, David B; Yadav, Rajbharan; Bulitta, Jürgen B; Williams, Charlotte C; Porter, Christopher J H; Landersdorfer, Cornelia B; Kaminskas, Lisa M

2016-04-04

The lymphatic system is a major conduit by which many diseases spread and proliferate. There is therefore increasing interest in promoting better lymphatic drug targeting. Further, antibody fragments such as Fabs have several advantages over full length monoclonal antibodies but are subject to rapid plasma clearance, which can limit the lymphatic exposure and activity of Fabs against lymph-resident diseases. This study therefore explored ideal PEGylation strategies to maximize biological activity and lymphatic exposure using trastuzumab Fab' as a model. Specifically, the Fab' was conjugated with single linear 10 or 40 kDa PEG chains at the hinge region. PEGylation led to a 3-4-fold reduction in binding affinity to HER2, but antiproliferative activity against HER2-expressing BT474 cells was preserved. Lymphatic pharmacokinetics were then examined in thoracic lymph duct cannulated rats after intravenous and subcutaneous dosing at 2 mg/kg, and the data were evaluated via population pharmacokinetic modeling. The Fab' displayed limited lymphatic exposure, but conjugation of 10 kDa PEG improved exposure by approximately 11- and 5-fold after intravenous (15% dose collected in thoracic lymph over 30 h) and subcutaneous (9%) administration, respectively. Increasing the molecular weight of the PEG to 40 kDa, however, had no significant impact on lymphatic exposure after intravenous (14%) administration and only doubled lymphatic exposure after subcutaneous administration (18%) when compared to 10 kDa PEG-Fab'. The data therefore suggests that minimal PEGylation has the potential to enhance the exposure and activity of Fab's against lymph-resident diseases, while no significant benefit is achieved with very large PEGs.

Preparation and characterization of anodic films on AZ31B Mg alloy formed in the silicate electrolytes with ethylene glycol oligomers as additives

NASA Astrophysics Data System (ADS)

Zhu, Feng; Wang, Jinwei; Li, Shanghua; Zhang, Jin

2012-09-01

Oxide coatings are prepared on AZ31B Mg alloy in an environment-friendly electrolyte with additives by plasma electrolytic anodization, and the effect of ethylene glycol oligmers on the performances of the anodized film is investigated. Under a constant current density of 10 mA cm-2, the reaction overpotential of the silicate electrolytes with additives are found higher than that of the original electrolyte as measured by potential-time test. The EIS and DC polarization results reveal that the addition of PEG increases the impedance of the film and reduces its corrosion current density (Icorr) at least by one order of magnitude. The surface morphologies are more and more compact and homogeneous with the increase in EG numbers, while a rougher surface appeared again if the PEG4000 is used as observed by SEM. As detected by XRD, the anodic films are found mainly consist of MgO, MgSiO3 and Mg2SiO4, and their relative amounts are related to the lengths of EGs, resulting in the differences in morphology and anticorrosion variations. Furthermore, the improvement in abrasive resistance of the anodic film formed in the electrolyte with PEG1000 may be attributed to its much more compact surface and the incorporation of ductile PEG chains among those oxides.

Smart pH- and reduction-dual-responsive folate-PEG-coated polymeric lipid vesicles for tumor-triggered targeted drug delivery

NASA Astrophysics Data System (ADS)

Wang, Sheng; Wang, Hanjie; Liu, Zhongyun; Wang, Liangliang; Wang, Xiaomin; Su, Lin; Chang, Jin

2014-06-01

To improve their therapeutic index, designed nanocarriers should preferentially accumulate in tumor tissues and then rapidly enter tumor cells to release the encapsulated drugs in a triggered manner. In this article, a new kind of a smart pH- and reduction-dual-responsive drug delivery system based on folate-PEG-coated polymeric lipid vesicles (FPPLVs) formed from amphiphilic dextran derivatives was designed and prepared successfully. PEG chains with pH-sensitive hydrazone bonds, stearyl alcohol (SA) chains with reduction-sensitive disulfide bonds and folate were connected to a dextran main chain. The newly developed FPPLVs had a nano-sized structure (~50 nm) with a PEG coating. The in vitro DOX release profiles showed that the FPPLVs achieved a triggered drug release in response to acidic pH and reducing environments due to the cleavage of hydrazone bonds and disulfide bonds. It has also been demonstrated by an in vitro cellular uptake study that the FPPLVs lose their PEG coating as well as expose the folate in acidic conditions, which allows them to efficiently enter tumor cells through ligand-receptor interactions. In vitro cytotoxicity measurements also confirmed that FPPLVs exhibited pronounced antitumor activity against HeLa cells. These results suggest that FPPLVs are promising carriers for smart antitumor drug delivery applications.To improve their therapeutic index, designed nanocarriers should preferentially accumulate in tumor tissues and then rapidly enter tumor cells to release the encapsulated drugs in a triggered manner. In this article, a new kind of a smart pH- and reduction-dual-responsive drug delivery system based on folate-PEG-coated polymeric lipid vesicles (FPPLVs) formed from amphiphilic dextran derivatives was designed and prepared successfully. PEG chains with pH-sensitive hydrazone bonds, stearyl alcohol (SA) chains with reduction-sensitive disulfide bonds and folate were connected to a dextran main chain. The newly developed FPPLVs had a nano-sized structure (~50 nm) with a PEG coating. The in vitro DOX release profiles showed that the FPPLVs achieved a triggered drug release in response to acidic pH and reducing environments due to the cleavage of hydrazone bonds and disulfide bonds. It has also been demonstrated by an in vitro cellular uptake study that the FPPLVs lose their PEG coating as well as expose the folate in acidic conditions, which allows them to efficiently enter tumor cells through ligand-receptor interactions. In vitro cytotoxicity measurements also confirmed that FPPLVs exhibited pronounced antitumor activity against HeLa cells. These results suggest that FPPLVs are promising carriers for smart antitumor drug delivery applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr00843j

Molecular-dynamics simulations of self-assembled monolayers (SAM) on parallel computers

NASA Astrophysics Data System (ADS)

Vemparala, Satyavani

The purpose of this dissertation is to investigate the properties of self-assembled monolayers, particularly alkanethiols and Poly (ethylene glycol) terminated alkanethiols. These simulations are based on realistic interatomic potentials and require scalable and portable multiresolution algorithms implemented on parallel computers. Large-scale molecular dynamics simulations of self-assembled alkanethiol monolayer systems have been carried out using an all-atom model involving a million atoms to investigate their structural properties as a function of temperature, lattice spacing and molecular chain-length. Results show that the alkanethiol chains tilt from the surface normal by a collective angle of 25° along next-nearest neighbor direction at 300K. At 350K the system transforms to a disordered phase characterized by small tilt angle, flexible tilt direction, and random distribution of backbone planes. With increasing lattice spacing, a, the tilt angle increases rapidly from a nearly zero value at a = 4.7A to as high as 34° at a = 5.3A at 300K. We also studied the effect of end groups on the tilt structure of SAM films. We characterized the system with respect to temperature, the alkane chain length, lattice spacing, and the length of the end group. We found that the gauche defects were predominant only in the tails, and the gauche defects increased with the temperature and number of EG units. Effect of electric field on the structure of poly (ethylene glycol) (PEG) terminated alkanethiol self assembled monolayer (SAM) on gold has been studied using parallel molecular dynamics method. An applied electric field triggers a conformational transition from all-trans to a mostly gauche conformation. The polarity of the electric field has a significant effect on the surface structure of PEG leading to a profound effect on the hydrophilicity of the surface. The electric field applied anti-parallel to the surface normal causes a reversible transition to an ordered state in which the oxygen atoms are exposed. On the other hand, an electric field applied in a direction parallel to the surface normal introduces considerable disorder in the system and the oxygen atoms are buried inside.

Biocellulose-based flexible magnetic paper

NASA Astrophysics Data System (ADS)

Barud, H. S.; Tercjak, A.; Gutierrez, J.; Viali, W. R.; Nunes, E. S.; Ribeiro, S. J. L.; Jafellici, M.; Nalin, M.; Marques, R. F. C.

2015-05-01

Biocellulose or bacterial cellulose (BC) is a biocompatible (nano) material produced with a three-dimensional network structure composed of microfibrils having nanometric diameters obtained by the Gluconacetobacter xylinus bacteria. BC membranes present relatively high porosity, allowing the incorporation or synthesis in situ of inorganic nanoparticles for multifunctional applications and have been used as flexible membranes for incorporation of magnetic nanocomposite. In this work, highly stable superparamagnetic iron oxide nanoparticles (SPION), functionalized with polyethylene glycol (PEG), with an average diameter of 5 nm and a saturation magnetization of 41 emu/g at 300 K were prepared. PEG-Fe2O3 hybrid was dispersed by mixing a pristine BC membrane in a stable aqueous dispersion of PEG-SPION. The PEG chains at PEG-SPION's surface provide a good permeability and strong affinity between the BC chains and SPION through hydrogen-bonding interactions. PEG-SPION also allow the incorporation of higher content of nanoparticles without compromising the mechanical properties of the nanocomposite. Structural and magnetic properties of the composite have been characterized by XRD, SEM, energy-dispersive X-ray spectroscopy (EDX), magnetization, Raman spectroscopy, and magnetic force microscopy.

Characterization, efficacy, pharmacokinetics, and biodistribution of 5kDa mPEG modified tetrameric canine uricase variant.

PubMed

Zhang, Chun; Fan, Kai; Luo, Hua; Ma, Xuefeng; Liu, Riyong; Yang, Li; Hu, Chunlan; Chen, Zhenmin; Min, Zhiqiang; Wei, Dongzhi

2012-07-01

PEGylated uricase is a promising anti-gout drug, but the only commercially marketed 10kDa mPEG modified porcine-like uricase (Pegloticase) can only be used for intravenous infusion. In this study, tetrameric canine uricase variant was modified by covalent conjugation of all accessible ɛ amino sites of lysine residues with a smaller 5kDa mPEG (mPEG-UHC). The average modification degree and PEGylation homogeneity were evaluated. Approximately 9.4 5 kDa mPEG chains were coupled to each monomeric uricase and the main conjugates contained 7-11 mPEG chains per subunit. mPEG-UHC showed significantly therapeutic or preventive effect on uric acid nephropathy and acute urate arthritis based on three different animal models. The clearance rate from an intravenous injection of mPEG-UHC varied significantly between species, at 2.61 mL/h/kg for rats and 0.21 mL/h/kg for monkeys. The long elimination half-life of mPEG-UHC in non-human primate (191.48 h, intravenous injection) indicated the long-term effects in humans. Moreover, the acceptable bioavailability of mPEG-UHC after subcutaneous administration in monkeys (94.21%) suggested that subcutaneous injection may be regarded as a candidate administration route in clinical trails. Non-specific tissue distribution was observed after administration of (125)I-labeled mPEG-UHC in rats, and elimination by the kidneys into the urine is the primary excretion route. Copyright © 2012 Elsevier B.V. All rights reserved.

Formation of protein complex with the aid of polyethylene glycol for deproteinized natural rubber latex

NASA Astrophysics Data System (ADS)

Wei, Lim Keuw; Ing, Wong Kwee; Badri, Khairiah Haji; Ban, Wong Chong

2013-11-01

The effect of polyethylene glycol (PEG) as a deproteinizing agent in commercial natural rubber latex (NRL) onto the physicochemical properties of the NRL was investigated. Three types of PEG were used namely PEG200, PEG4000 and PEG20000 (molecular weight of 200, 4000 and 20000 g/mol respectively). The optimum amount of PEG in NRL was determined from viscosity changes, protein content and Fourier Transform Infrared spectroscopy. Level of protein reduction was affected by molecular weight of PEG. The addition of PEG in NRL reduced the protein content of NRL (3.30 %) to the lowest (2.01 %) at 0.40 phr of PEG200 due to more attractive hydrophobic interactions between short chains PEG compared to PEG4000 (2.24%) and PEG20000 (2.15%). This was verified through FTIR spectroscopy analysis by observing the primary and secondary amide peak where PEG4000 has lesser absorption at the region compared to with PEG20000.

Molecular Dynamics Studies of Polyethylene Oxide and Polyethylene Glycol: Hydrodynamic Radius and Shape Anisotropy

PubMed Central

Lee, Hwankyu; Venable, Richard M.; MacKerell, Alexander D.; Pastor, Richard W.

2008-01-01

A revision (C35r) to the CHARMM ether force field is shown to reproduce experimentally observed conformational populations of dimethoxyethane. Molecular dynamics simulations of 9, 18, 27, and 36-mers of polyethylene oxide (PEO) and 27-mers of polyethylene glycol (PEG) in water based on C35r yield a persistence length λ = 3.7 Å, in quantitative agreement with experimentally obtained values of 3.7 Å for PEO and 3.8 Å for PEG; agreement with experimental values for hydrodynamic radii of comparably sized PEG is also excellent. The exponent υ relating the radius of gyration and molecular weight (\\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}R_{{\\mathrm{g}}}{\\propto}M_{{\\mathrm{w}}}^{{\\upsilon}}\\end{equation*}\\end{document}) of PEO from the simulations equals 0.515 ± 0.023, consistent with experimental observations that low molecular weight PEG behaves as an ideal chain. The shape anisotropy of hydrated PEO is 2.59:1.44:1.00. The dimension of the middle length for each of the polymers nearly equals the hydrodynamic radius \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}R_{{\\mathrm{h}}}\\end{equation*}\\end{document}obtained from diffusion measurements in solution. This explains the correspondence of \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}R_{{\\mathrm{h}}}\\end{equation*}\\end{document} and \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}R_{{\\mathrm{p}}},\\end{equation*}\\end{document} the pore radius of membrane channels: a polymer such as PEG diffuses with its long axis parallel to the membrane channel, and passes through the channel without substantial distortion. PMID:18456821

Measurements of Attractive Forces between Proteins and End-Grafted Poly(Ethylene Glycol) Chains

NASA Astrophysics Data System (ADS)

Sheth, S. R.; Leckband, D.

1997-08-01

The surface force apparatus was used to measure directly the molecular forces between streptavidin and lipid bilayers displaying grafted Mr 2,000 poly(ethylene glycol) (PEG). These measurements provide direct evidence for the formation of relatively strong attractive forces between PEG and protein. At low compressive loads, the forces were repulsive, but they became attractive when the proteins were pressed into the polymer layer at higher loads. The adhesion was sufficiently robust that separation of the streptavidin and PEG uprooted anchored polymer from the supporting membrane. These interactions altered the properties of the grafted chains. After the onset of the attraction, the polymer continued to bind protein for several hours. The changes were not due to protein denaturation. These data demonstrate directly that the biological activity of PEG is not due solely to properties of simple polymers such as the excluded volume. It is also coupled to the competitive interactions between solvent and other materials such as proteins for the chain segments and to the ability of this material to adopt higher order intrachain structures.

Importance of poly(ethylene glycol) conformation for the synthesis of silver nanoparticles in aqueous solution

USDA-ARS?s Scientific Manuscript database

In the formation of silver nanoparticles (NPs) using silver nitrate in a poly(ethylene glycol) (PEG) aqueous solution, which acts as both a reducing and stabilizing agent, the PEG chain structure was found to play a significant role. Even though PEG 100 (100 kg/mol) has limited reducing sites of hyd...

Stabilization of bacterially expressed erythropoietin by single site-specific introduction of short branched PEG chains at naturally occurring glycosylation sites.

PubMed

Hoffmann, E; Streichert, K; Nischan, N; Seitz, C; Brunner, T; Schwagerus, S; Hackenberger, C P R; Rubini, M

2016-05-24

The covalent attachment of polyethylene glycol (PEG) to therapeutic proteins can improve their physicochemical properties. In this work we utilized the non-natural amino acid p-azidophenylalanine (pAzF) in combination with the chemoselective Staudinger-phosphite reaction to install branched PEG chains to recombinant unglycosylated erythropoietin (EPO) at each single naturally occurring glycosylation site. PEGylation with two short 750 or 2000 Da PEG units at positions 24, 38, or 83 significantly decreased unspecific aggregation and proteolytic degradation while biological activity in vitro was preserved or even increased in comparison to full-glycosylated EPO. This site-specific bioconjugation approach permits to analyse the impact of PEGylation at single positions. These results represent an important step towards the engineering of site-specifically modified EPO variants from bacterial expression with increased therapeutic efficacy.

Lamellar biogels comprising fluid membranes with a newly synthesized class of polyethylene glycol-surfactants

NASA Astrophysics Data System (ADS)

Warriner, Heidi E.; Davidson, Patrick; Slack, Nelle L.; Schellhorn, Matthias; Eiselt, Petra; Idziak, Stefan H. J.; Schmidt, Hans-Werner; Safinya, Cyrus R.

1997-09-01

A series of four polymer-surfactant macromolecules, each consisting of a double-chain hydrophobic moiety attached onto a monofunctional polyethylene glycol (PEG) polymer chain, were synthesized in order to study their effect upon the fluid lamellar liquid crystalline (Lα) phase of the dimyristoylphosphatidylcholine/pentanol/water system. The main finding of this study is that the addition of these compounds induces a new lamellar gel, called Lα,g. We have determined the phase diagrams as a function of PEG-surfactant concentration, cPEG, and weight fraction water, ΦW. All phase diagrams are qualitatively similar and show the existence of the gel. Unlike more common polymer physical gels, this gel can be induced either by increasing cPEG or by adding water at constant cPEG. In particular, less polymer is required for gelation as water concentration increases. Moreover, the gel phase is attained at concentrations of PEG-surfactant far below that required for classical polymer gels and is stable at temperatures comparable to the lower critical solution temperature of free PEG-water mixtures. Small angle x-ray experiments demonstrate the lamellar structure of the gel phase, while wide angle x-ray scattering experiments prove that the structure is Lα, not Lβ' (a common chain-ordered phase which is also a gel). The rheological behavior of the Lα,g phase demonstrates the existence of three dimensional elastic properties. Polarized light microscopy of Lα,g samples reveals that the Lα,g is induced by a proliferation of defect structures, including whispy lines, spherulitic defects, and a nematiclike Schlieren texture. We propose a model of topological defects created by the aggregation of PEG-surfactant into highly curved regions within the membranes. This model accounts for both the inverse relationship between ΦW and cPEG observed along the gel transition line and the scaling dependence of the interlayer spacing at the gel transition with the PEG molecular weight. These Lα hydrogels could serve as the matrix for membrane-anchored peptides, proteins or other drug molecules, creating a "bioactive gel" with mechanical stability deriving from the polymer-lipid minority component.

Multifunctional superparamagnetic iron oxide nanoparticles for combined chemotherapy and hyperthermia cancer treatment

NASA Astrophysics Data System (ADS)

Quinto, Christopher A.; Mohindra, Priya; Tong, Sheng; Bao, Gang

2015-07-01

Superparamagnetic iron oxide (SPIO) nanoparticles have the potential for use as a multimodal cancer therapy agent due to their ability to carry anticancer drugs and generate localized heat when exposed to an alternating magnetic field, resulting in combined chemotherapy and hyperthermia. To explore this potential, we synthesized SPIOs with a phospholipid-polyethylene glycol (PEG) coating, and loaded Doxorubicin (DOX) with a 30.8% w/w loading capacity when the PEG length is optimized. We found that DOX-loaded SPIOs exhibited a sustained DOX release over 72 hours where the release kinetics could be altered by the PEG length. In contrast, the heating efficiency of the SPIOs showed minimal change with the PEG length. With a core size of 14 nm, the SPIOs could generate sufficient heat to raise the local temperature to 43 °C, sufficient to trigger apoptosis in cancer cells. Further, we found that DOX-loaded SPIOs resulted in cell death comparable to free DOX, and that the combined effect of DOX and SPIO-induced hyperthermia enhanced cancer cell death in vitro. This study demonstrates the potential of using phospholipid-PEG coated SPIOs for chemotherapy-hyperthermia combinatorial cancer treatment with increased efficacy.Superparamagnetic iron oxide (SPIO) nanoparticles have the potential for use as a multimodal cancer therapy agent due to their ability to carry anticancer drugs and generate localized heat when exposed to an alternating magnetic field, resulting in combined chemotherapy and hyperthermia. To explore this potential, we synthesized SPIOs with a phospholipid-polyethylene glycol (PEG) coating, and loaded Doxorubicin (DOX) with a 30.8% w/w loading capacity when the PEG length is optimized. We found that DOX-loaded SPIOs exhibited a sustained DOX release over 72 hours where the release kinetics could be altered by the PEG length. In contrast, the heating efficiency of the SPIOs showed minimal change with the PEG length. With a core size of 14 nm, the SPIOs could generate sufficient heat to raise the local temperature to 43 °C, sufficient to trigger apoptosis in cancer cells. Further, we found that DOX-loaded SPIOs resulted in cell death comparable to free DOX, and that the combined effect of DOX and SPIO-induced hyperthermia enhanced cancer cell death in vitro. This study demonstrates the potential of using phospholipid-PEG coated SPIOs for chemotherapy-hyperthermia combinatorial cancer treatment with increased efficacy. Electronic supplementary information (ESI) available: Core size distribution; temperature increase for specific absorption rate calculations; effect of DOX loading on zeta potential; combined effect of hyperthermia and free DOX; cell morphology following DOX/hyperthermia treatment. See DOI: 10.1039/c5nr02718g

Interaction of polyhedral oligomeric silsesquioxanes and dipalmitoylphosphatidylcholine at the air/water interface: Thermodynamic and rheological study.

PubMed

Skrzypiec, M; Georgiev, G As; Rojewska, M; Prochaska, K

2017-10-01

Polyhedral oligomeric silsesquioxanes (POSS) derivatives containing open silsesquioxane cage bear great potential for biomedical applications and therefore their lateral interactions with phospholipids, major biomembranes and drug vehicles constituent, should be studied in detail. That is why the properties of surface films by two POSS-derivatives, POSS-polyethylene glycol (POSS-PEG) and POSS-perfluoroalkyl (POSS-OFP), pure and in presence of 1,2-dipalmitoyl-sn-glycerol-3-phosphocholine (DPPC) were studied using Langmuir surface balance. Side chains of opposite nature (PEG is hydrophilic; OFP is hydrophobic) were selected, so that to evaluate their impact on polymers' surface properties. Two types of measurements were performed: (i) the miscibility of POSS-derivatives with DPPC was evaluated via thermodynamic analysis of the surface pressure (π)-area (A) isotherms and (ii) the dilatational rheology of selected POSS-polymer containing films was studied by the stress relaxation method. Fourier transformation analysis of the relaxation transients allows to access films' dynamic interfacial properties in broad frequency range (10 -5 -1Hz). Film morphology was monitored with Brewster Angle Microscopy. PEG moiety enabled POSS-PEG to stably incorporate in DPPC films, modifying their equilibrium and dynamic properties. In contrast OFP chains excluded from interactions with other molecules and diminished PEG-OFP amphiphilicity. Therefore at high packing densities (π≥25mN/m) PEG-OFP was expelled from the air/water interface in DPPC/PEG-OFP mixtures, and the binary films equilibrium and dynamic surface properties were determined primarily by DPPC. Thus the choice of POSS side chains can play key role in biomedical applications depending on whether strong or weak incorporation of POSS-polymers in lipid environment is aimed for. Copyright © 2017 Elsevier B.V. All rights reserved.

Temperature-Dependent Implicit-Solvent Model of Polyethylene Glycol in Aqueous Solution.

PubMed

Chudoba, Richard; Heyda, Jan; Dzubiella, Joachim

2017-12-12

A temperature (T)-dependent coarse-grained (CG) Hamiltonian of polyethylene glycol/oxide (PEG/PEO) in aqueous solution is reported to be used in implicit-solvent material models in a wide temperature (i.e., solvent quality) range. The T-dependent nonbonded CG interactions are derived from a combined "bottom-up" and "top-down" approach. The pair potentials calculated from atomistic replica-exchange molecular dynamics simulations in combination with the iterative Boltzmann inversion are postrefined by benchmarking to experimental data of the radius of gyration. For better handling and a fully continuous transferability in T-space, the pair potentials are conveniently truncated and mapped to an analytic formula with three structural parameters expressed as explicit continuous functions of T. It is then demonstrated that this model without further adjustments successfully reproduces other experimentally known key thermodynamic properties of semidilute PEG solutions such as the full equation of state (i.e., T-dependent osmotic pressure) for various chain lengths as well as their cloud point (or collapse) temperature.

Poly(ethylene glycol)s in Semidilute Regime: Radius of Gyration in the Bulk and Partitioning into a Nanopore

DOE PAGES

Gurnev, Philip A.; Stanley, Christopher B.; Aksoyoglu, M. Alphan; ...

2017-03-09

In this work, using two approaches, small-angle neutron scattering (SANS) from bulk solutions and nanopore conductance-fluctuation analysis, we studied structural and dynamic features of poly(ethylene glycol) (PEG) water/salt solutions in the dilute and semidilute regimes. SANS measurements on PEG 3400 at the zero-average contrast yielded the single chain radius of gyration (R g) over 1–30 wt %. We observed a small but statistically reliable decrease in R g with increasing PEG concentration: at 30 wt % the chain contracts by a factor of 0.94. Analyzing conductance fluctuations of the α-hemolysin nanopore in the mixtures of PEG 200 with PEG 3400,more » we demonstrated that polymer partitioning into the nanopore is mostly due to PEG 200. Specifically, for a 1:1 wt/wt mixture the smaller polymer dominates to the extent that only about 1/25 of the nanopore volume is taken by the larger polymer. In conclusion, these findings advance our conceptual and quantitative understanding of nanopore polymer partitioning; they also support the main assumptions of the recent “polymers-pushing-polymers” model.« less

Modification of Propellant Binder Network for Improvement of Mechanical Properties

DTIC Science & Technology

1984-12-01

skeletal atoms) is more beneficial than 22 mole % of the shorter PEG 3350 (230 skeletal atoms) or 25 mole % of shorter PCP 0260 (180 skeletal atoms). One...of the reasons may be that a higher degree of strain-induced crystalliza- tion of PEG 8000 occurs compared with PEG 3350 or PCP 0260. 4.8 Effect of...prepolymer rubbers. Also, the stress capability of the cured rubbers is improved compared to the long chain prepolymer rubbers. Polyethylene glycol 8000 ( PEG

Biocompatible fluorinated polyglycerols for droplet microfluidics as an alternative to PEG-based copolymer surfactants.

PubMed

Wagner, Olaf; Thiele, Julian; Weinhart, Marie; Mazutis, Linas; Weitz, David A; Huck, Wilhelm T S; Haag, Rainer

2016-01-07

In droplet-based microfluidics, non-ionic, high-molecular weight surfactants are required to stabilize droplet interfaces. One of the most common structures that imparts stability as well as biocompatibility to water-in-oil droplets is a triblock copolymer surfactant composed of perfluoropolyether (PFPE) and polyethylene glycol (PEG) blocks. However, the fast growing applications of microdroplets in biology would benefit from a larger choice of specialized surfactants. PEG as a hydrophilic moiety, however, is a very limited tool in surfactant modification as one can only vary the molecular weight and chain-end functionalization. In contrast, linear polyglycerol offers further side-chain functionalization to create custom-tailored, biocompatible droplet interfaces. Herein, we describe the synthesis and characterization of polyglycerol-based triblock surfactants with tailored side-chain composition, and exemplify their application in cell encapsulation and in vitro gene expression studies in droplet-based microfluidics.

INTRACELLULAR TARGETING OF THE ONCOGENIC MUC1-C PROTEIN WITH A NOVEL GO-203 NANOPARTICLE FORMULATION

PubMed Central

Hasegawa, Masanori; Sinha, Raj Kumar; Kumar, Manoj; Alam, Maroof; Yin, Li; Raina, Deepak; Kharbanda, Akriti; Panchamoorthy, Govind; Gupta, Dikshi; Singh, Harpal; Kharbanda, Surender; Kufe, Donald

2015-01-01

Purpose The MUC1-C oncoprotein is an intracellular target that is druggable with cell-penetrating peptide inhibitors. However, development of peptidyl drugs for treating cancer has been a challenge because of unfavorable pharmacokinetic parameters and limited cell penetrating capabilities. Experimental Design Encapsulation of the MUC1-C inhibitor, GO-203, in novel polymeric nanoparticles (NPs) was studied for effects on intracellular targeting of MUC1-C signaling and function. Results Our results show that loading GO-203 into tetrablock polylactic acid (PLA)-polyethylene glycol (PEG)-polypropylene glycol (PPG)-PEG copolymers is achievable and, notably, is enhanced by increasing PEG chain length. Additionally, we found that release of GO-203 from these NPs is controllable over at least 7 days. GO-203/NP treatment of MUC1-C-positive breast and lung cancer cells in vitro was more active with less frequent dosing than that achieved with non-encapsulated GO-203. Moreover, treatment with GO-203/NPs blocked MUC1-C homodimerization, consistent with on-target effects. GO-203/NP treatment was also effective in downregulating TIGAR, disrupting redox balance and inhibiting the self-renewal capacity of cancer cells. Significantly, weekly administration of GO-203/NPs to mice bearing syngeneic or xenograft tumors was associated with regressions that were comparable to those found when dosing on a daily basis with GO-203. Conclusions These findings thus define an effective approach for (i) sustained administration of GO-203 in polymeric PLA-(PEG-PPG-PEG) NPs to target MUC1-C in cancer cells and (ii) the potential delivery of other anti-cancer peptide drugs. PMID:25712682

Noncovalent PEGylation through Protein-Polyelectrolyte Interaction: Kinetic Experiment and Molecular Dynamics Simulation.

PubMed

Kurinomaru, Takaaki; Kuwada, Kengo; Tomita, Shunsuke; Kameda, Tomoshi; Shiraki, Kentaro

2017-07-20

Noncovalent binding of polyethylene glycol (PEG) to a protein surface is a unique protein handling technique to control protein function and stability. A diblock copolymer containing PEG and polyelectrolyte chains (PEGylated polyelectrolyte) is a promising candidate for noncovalent attachment of PEG to a protein surface because of the binding through multiple electrostatic interactions without protein denaturation. To obtain a deeper understanding of protein-polyelectrolyte interaction at the molecular level, we investigated the manner in which cationic PEGylated polyelectrolyte binds to anionic α-amylase in enzyme kinetic experiments and molecular dynamics (MD) simulations. Cationic PEG-block-poly(N,N-dimethylaminoethyl) (PEG-b-PAMA) inhibited the enzyme activity of anionic α-amylase due to binding of PAMA chains. Enzyme kinetics revealed that the inhibition of α-amylase activity by PEG-b-PAMA is noncompetitive inhibition manner. In MD simulations, the PEG-b-PAMA molecule was initially located at six different placements of the x-, y-, and z-axis ±20 Å from the center of α-amylase, which showed that the PEG-b-PAMA nonspecifically bound to the α-amylase surface, corresponding to the noncompetitive inhibition manner that stems from the polymer binding to an enzyme surface other than the active site. In addition, the enzyme activity of α-amylase in the presence of PEG-b-PAMA was not inhibited by increasing the ionic strength, consistent with the MD simulation; i.e., PEG-b-PAMA did not interact with α-amylase in high ionic strength conditions. The results reported in this paper suggest that enzyme inhibition by PEGylated polyelectrolyte can be attributed to the random electrostatic interaction between protein and polyelectrolyte.

Multifunctional superparamagnetic iron oxide nanoparticles for combined chemotherapy and hyperthermia cancer treatment.

PubMed

Quinto, Christopher A; Mohindra, Priya; Tong, Sheng; Bao, Gang

2015-08-07

Superparamagnetic iron oxide (SPIO) nanoparticles have the potential for use as a multimodal cancer therapy agent due to their ability to carry anticancer drugs and generate localized heat when exposed to an alternating magnetic field, resulting in combined chemotherapy and hyperthermia. To explore this potential, we synthesized SPIOs with a phospholipid-polyethylene glycol (PEG) coating, and loaded Doxorubicin (DOX) with a 30.8% w/w loading capacity when the PEG length is optimized. We found that DOX-loaded SPIOs exhibited a sustained DOX release over 72 hours where the release kinetics could be altered by the PEG length. In contrast, the heating efficiency of the SPIOs showed minimal change with the PEG length. With a core size of 14 nm, the SPIOs could generate sufficient heat to raise the local temperature to 43 °C, sufficient to trigger apoptosis in cancer cells. Further, we found that DOX-loaded SPIOs resulted in cell death comparable to free DOX, and that the combined effect of DOX and SPIO-induced hyperthermia enhanced cancer cell death in vitro. This study demonstrates the potential of using phospholipid-PEG coated SPIOs for chemotherapy-hyperthermia combinatorial cancer treatment with increased efficacy.

Controlling the Formation of Ionic-Liquid-based Aqueous Biphasic Systems by Changing the Hydrogen-Bonding Ability of Polyethylene Glycol End Groups.

PubMed

Pereira, Jorge F B; Kurnia, Kiki A; Freire, Mara G; Coutinho, João A P; Rogers, Robin D

2015-07-20

The formation of aqueous biphasic systems (ABS) when mixing aqueous solutions of polyethylene glycol (PEG) and an ionic liquid (IL) can be controlled by modifying the hydrogen-bond-donating/-accepting ability of the polymer end groups. It is shown that the miscibility/immiscibility in these systems stems from both the solvation of the ether groups in the oxygen chain and the ability of the PEG terminal groups to preferably hydrogen bond with water or the anion of the salt. The removal of even one hydrogen bond in PEG can noticeably affect the phase behavior, especially in the region of the phase diagram in which all the ethylene oxide (EO) units of the polymeric chain are completely solvated. In this region, removing or weakening the hydrogen-bond-donating ability of PEG results in greater immiscibility, and thus, in a higher ability to form ABS, as a result of the much weaker interactions between the IL anion and the PEG end groups. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The bundling of actin with polyethylene glycol 8000 in the presence and absence of gelsolin.

PubMed Central

Goverman, J; Schick, L A; Newman, J

1996-01-01

Actin filament and bundle formation occur in the cytosol under conditions of very high total macromolecular concentration. In this study we have utilized the inert molecule polyethylene glycol 8000 (PEG) as a means of simulating crowded conditions in vitro. Column-purified Ca-actin was polymerized in the absence and presence of gelsolin (to regulate mean filament lengths between 50 and 5000 mers) and PEG (2-8%) using various concentrations of KCl and/or 2 mM divalent cations. Bundling was characterized by the scattered light intensity and mean diffusion coefficients obtained from dynamic light scattering, as well as by fluorescence and phase-contrast microscopy. The minimum concentration of KCl required for bundling decreases both with increasing concentration of PEG at a fixed mean filament length, and with decreasing filament length at a fixed concentration of PEG. In the absence of divalent cation, bundling is reversible on dilution, as determined by intensity levels, diffusion coefficients, and microscopy. However, with either 2 mM Mg2+ or Ca2+ added, bundling is irreversible under conditions of higher PEG concentrations or longer filaments, indicating that osmotic pressure effects cannot fully explain actin bundling with PEG. Weaker divalent cation-binding sites on actin as well as disulfide bonds appear to be involved in the irreversible bundling. Images FIGURE 7 PMID:8874022

Clonazepam release from bioerodible hydrogels based on semi-interpenetrating polymer networks composed of poly(epsilon-caprolactone) and poly(ethylene glycol) macromer.

PubMed

Cho, C S; Han, S Y; Ha, J H; Kim, S H; Lim, D Y

1999-04-30

Poly(ethylene glycol)(PEG) macromers terminated with acrylate groups and semi-interpenetrating polymer networks (SIPNs) composed of poly(epsilon-caprolactone)(PCL) and PEG macromer were synthesized to obtain a bioerodible hydrogel. Polymerization of PEG macromer resulted in the formation of cross-linked gels due to the multifunctionality of macromer. Glass transition temperature (Tg) and melting temperature (Tm) of PEG networks and PCL in the SIPNs were inner-shifted, indicating an interpenetration of PCL and PEG chains. Water content in the SIPNs increased with increasing PEG weight fraction due to the hydrophilicity of PEG. The amount of clonazepam (CNZ) released from the SIPNs increased with higher content in the SIPNs, lower drug loading, lower concentration of PEG macromer during the SIPNs preparation, and higher molecular weight of PEG. In particular, a combination with low PEG content and low CNZ solubility in water led to long-term constant release from these matrices in vitro and in vivo. Copyright.

Self-assembly of core-polyethylene glycol-lipid shell (CPLS) nanoparticles and their potential as drug delivery vehicles

NASA Astrophysics Data System (ADS)

Shen, Zhiqiang; Loe, David T.; Awino, Joseph K.; Kröger, Martin; Rouge, Jessica L.; Li, Ying

2016-08-01

Herein a new multifunctional formulation, referred to as a core-polyethylene glycol-lipid shell (CPLS) nanoparticle, has been proposed and studied in silico via large scale coarse-grained molecular dynamics simulations. A PEGylated core with surface tethered polyethylene glycol (PEG) chains is used as the starting configuration, where the free ends of the PEG chains are covalently bonded with lipid molecules (lipid heads). A complete lipid bilayer is formed at the surface of the PEGylated particle core upon addition of free lipids, driven by the hydrophobic properties of the lipid tails, leading to the formation of a CPLS nanoparticle. The self-assembly process is found to be sensitive to the grafting density and molecular weight of the tethered PEG chains, as well as the amount of free lipids added. At low grafting densities the assembly of CPLS nanoparticles cannot be accomplished. As demonstrated by simulations, a lipid bud/vesicle can be formed on the surface when an excess amount of free lipids is added at high grafting density. Therefore, the CPLS nanoparticles can only be formed under appropriate conditions of both PEG and free lipids. The CPLS nanoparticle has been recognized to be able to store a large quantity of water molecules, particularly with high molecular weight of PEG chains, indicating its capacity for carrying hydrophilic molecules such as therapeutic biomolecules or imaging agents. Under identical size and surface chemistry conditions of a liposome, it has been observed that the CPLS particle can be more efficiently wrapped by the lipid membrane, indicating its potential for a greater efficiency in delivering its hydrophilic cargo. As a proof-of-concept, the experimental realization of CPLS nanoparticles is explicitly demonstrated in this study. To test the capacity of the CPLS to store small molecule cargo a hydrophilic dye was successfully encapsulated in the particles' water soluble layer. The results of this study show the power and potential of simulation-driven approaches for guiding the design of more efficient nanomaterial delivery platforms.Herein a new multifunctional formulation, referred to as a core-polyethylene glycol-lipid shell (CPLS) nanoparticle, has been proposed and studied in silico via large scale coarse-grained molecular dynamics simulations. A PEGylated core with surface tethered polyethylene glycol (PEG) chains is used as the starting configuration, where the free ends of the PEG chains are covalently bonded with lipid molecules (lipid heads). A complete lipid bilayer is formed at the surface of the PEGylated particle core upon addition of free lipids, driven by the hydrophobic properties of the lipid tails, leading to the formation of a CPLS nanoparticle. The self-assembly process is found to be sensitive to the grafting density and molecular weight of the tethered PEG chains, as well as the amount of free lipids added. At low grafting densities the assembly of CPLS nanoparticles cannot be accomplished. As demonstrated by simulations, a lipid bud/vesicle can be formed on the surface when an excess amount of free lipids is added at high grafting density. Therefore, the CPLS nanoparticles can only be formed under appropriate conditions of both PEG and free lipids. The CPLS nanoparticle has been recognized to be able to store a large quantity of water molecules, particularly with high molecular weight of PEG chains, indicating its capacity for carrying hydrophilic molecules such as therapeutic biomolecules or imaging agents. Under identical size and surface chemistry conditions of a liposome, it has been observed that the CPLS particle can be more efficiently wrapped by the lipid membrane, indicating its potential for a greater efficiency in delivering its hydrophilic cargo. As a proof-of-concept, the experimental realization of CPLS nanoparticles is explicitly demonstrated in this study. To test the capacity of the CPLS to store small molecule cargo a hydrophilic dye was successfully encapsulated in the particles' water soluble layer. The results of this study show the power and potential of simulation-driven approaches for guiding the design of more efficient nanomaterial delivery platforms. Electronic supplementary information (ESI) available: Simulation protocol, simulation results for the self-assembly of CPLS nanoparticles, membrane wrapping and free energy change of grafted PEG polymers. See DOI: 10.1039/C6NR04134E

Tunable Pickering Emulsions with Environmentally Responsive Hairy Silica Nanoparticles.

PubMed

Liu, Min; Chen, Xiaoli; Yang, Zongpeng; Xu, Zhou; Hong, Liangzhi; Ngai, To

2016-11-30

Surface modification of the nanoparticles using surface anchoring of amphiphilic polymers offers considerable scope for the design of a wide range of brush-coated hybrid nanoparticles with tunable surface wettability that may serve as new class of efficient Pickering emulsifiers. In the present study, we prepared mixed polymer brush-coated nanoparticles by grafting ABC miktoarm star terpolymers consisting of poly(ethylene glycol), polystyrene, and poly[(3-triisopropyloxysilyl)propyl methacrylate] (μ-PEG-b-PS-b-PIPSMA) on the surface of silica nanoparticles. The wettability of the as-prepared nanoparticles can be precisely tuned by a change of solvent or host-guest complexation. 1 H NMR result confirmed that such wettability change is due to the reorganization of the polymer chain at the grafted layer. We show that this behavior can be used for stabilization and switching between water-in-oil (W/O) and oil-in-water (O/W) emulsions. For hairy particles initially dispersed in oil, W/O emulsions were always obtained with collapsed PEG chains and mobile PS chains at the grafted layer. However, initially dispersing the hairy particles in water resulted in O/W emulsions with collapsed PS chains and mobile PEG chains. When a good solvent for both PS and PEG blocks such as toluene was used, W/O emulsions were always obtained no matter where the hairy particles were dispersed. The wettability of the mixed polymer brush-coated silica particles can also be tuned by host-guest complexation between PEG block and α-CD. More importantly, our result showed that surprisingly the resultant mixed brush-coated hairy nanoparticles can be employed for the one-step production of O/W/O multiple emulsions that are not attainable from conventional Pickering emulsifiers. The functionalized hairy silica nanoparticles at the oil-water interface can be further linked together utilizing poly(acrylic acid) as the reversible linker to form supramolecular colloidosomes, which show pH-dependent release of cargo.

Elasticity of bilayers containing PEG lipids

NASA Astrophysics Data System (ADS)

Bivas, I.; Winterhalter, M.; Méléard, P.; Bothorel, P.

1998-02-01

The addition of lipids with a poly(ethylene glycol) head group (Stealth or grafted or PEG lipids) to a phosphatidylcholine bilayer changes the mechanical properties of the membrane. We calculate the dependences of the bending and stretching elasticities of the bilayer on the PEG lipid concentration and on the monomer number in its polymer chain. The role of the bending elasticity at blocked flip-flop of the pure bilayer is revealed.

RAFT Aqueous Dispersion Polymerization Yields Poly(ethylene glycol)-Based Diblock Copolymer Nano-Objects with Predictable Single Phase Morphologies

PubMed Central

2013-01-01

A poly(ethylene glycol) (PEG) macromolecular chain transfer agent (macro-CTA) is prepared in high yield (>95%) with 97% dithiobenzoate chain-end functionality in a three-step synthesis starting from a monohydroxy PEG113 precursor. This PEG113-dithiobenzoate is then used for the reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA). Polymerizations conducted under optimized conditions at 50 °C led to high conversions as judged by 1H NMR spectroscopy and relatively low diblock copolymer polydispersities (Mw/Mn < 1.25) as judged by GPC. The latter technique also indicated good blocking efficiencies, since there was minimal PEG113 macro-CTA contamination. Systematic variation of the mean degree of polymerization of the core-forming PHPMA block allowed PEG113-PHPMAx diblock copolymer spheres, worms, or vesicles to be prepared at up to 17.5% w/w solids, as judged by dynamic light scattering and transmission electron microscopy studies. Small-angle X-ray scattering (SAXS) analysis revealed that more exotic oligolamellar vesicles were observed at 20% w/w solids when targeting highly asymmetric diblock compositions. Detailed analysis of SAXS curves indicated that the mean number of membranes per oligolamellar vesicle is approximately three. A PEG113-PHPMAx phase diagram was constructed to enable the reproducible targeting of pure phases, as opposed to mixed morphologies (e.g., spheres plus worms or worms plus vesicles). This new RAFT PISA formulation is expected to be important for the rational and efficient synthesis of a wide range of biocompatible, thermo-responsive PEGylated diblock copolymer nano-objects for various biomedical applications. PMID:24400622

Micelles of enzymatically synthesized PEG-poly(amine-co-ester) block copolymers as pH-responsive nanocarriers for docetaxel delivery.

PubMed

Zhang, Xiaofang; Liu, Bo; Yang, Zhe; Zhang, Chao; Li, Hao; Luo, Xingen; Luo, Huiyan; Gao, Di; Jiang, Qing; Liu, Jie; Jiang, Zhaozhong

2014-03-01

A series of PEGylated poly(amine-co-ester) terpolymers were successfully synthesized in one step via lipase-catalyzed copolymerization of ω-pentadecalactone (PDL), diethyl sebacate (DES), and N-methyldiethanolamine (MDEA) comonomers in the presence of poly(ethylene glycol) methyl ether as a chain-terminating agent. The resultant amphiphilic poly(ethylene glycol)-poly(PDL-co-MDEA-co-sebacate) (PEG-PPMS) block copolymers consisted of hydrophilic PEG chain segments and hydrophobic random PPMS chain segments, which self-assembled in aqueous medium to form stable, nanosized micelles at physiological pH of 7.4. Upon decreasing the medium pH from 7.4 to 5.0, the copolymer micelles swell significantly due to protonation of the amino groups in the micelle PPMS cores. Correspondingly, docetaxel (DTX)-encapsulated PEG2K-PPMS copolymer micelles showed gradual sustained drug release at pH of 7.4, but remarkably accelerated DTX release at acidic pH of 5.0. The drug-loaded micelle particles were readily internalized by SK-BR-3 cancer cells and, compared to free DTX drug, DTX-loaded micelles of the copolymers with optimal compositions exhibited enhanced potency against the cells. Biodegradable PEG-PPMS copolymer micelles represent a new type of promising, pH-responsive nanocarriers for anticancer drug delivery, and the drug release rate from the micelles can be systematically controlled by both pH and the copolymer composition. Copyright © 2013 Elsevier B.V. All rights reserved.

Accessing the dynamics of end-grafted flexible polymer chains by atomic force-electrochemical microscopy. Theoretical modeling of the approach curves by the elastic bounded diffusion model and Monte Carlo simulations. Evidence for compression-induced lateral chain escape.

PubMed

Abbou, Jeremy; Anne, Agnès; Demaille, Christophe

2006-11-16

The dynamics of a molecular layer of linear poly(ethylene glycol) (PEG) chains of molecular weight 3400, bearing at one end a ferrocene (Fc) label and thiol end-grafted at a low surface coverage onto a gold substrate, is probed using combined atomic force-electrochemical microscopy (AFM-SECM), at the scale of approximately 100 molecules. Force and current approach curves are simultaneously recorded as a force-sensing microelectrode (tip) is inserted within the approximately 10 nm thick, redox labeled, PEG chain layer. Whereas the force approach curve gives access to the structure of the compressed PEG layer, the tip-current, resulting from tip-to-substrate redox cycling of the Fc head of the chain, is controlled by chain dynamics. The elastic bounded diffusion model, which considers the motion of the Fc head as diffusion in a conformational field, complemented by Monte Carlo (MC) simulations, from which the chain conformation can be derived for any degree of confinement, allows the theoretical tip-current approach curve to be calculated. The experimental current approach curve can then be very satisfyingly reproduced by theory, down to a tip-substrate separation of approximately 2 nm, using only one adjustable parameter characterizing the chain dynamics: the effective diffusion coefficient of the chain head. At closer tip-substrate separations, an unpredicted peak is observed in the experimental current approach curve, which is shown to find its origin in a compression-induced escape of the chain from within the narrowing tip-substrate gap. MC simulations provide quantitative support for lateral chain elongation as the escape mechanism.

Plasticization of poly(lactic acid) using different molecular weight of Poly(ethylene glycol)

NASA Astrophysics Data System (ADS)

Septevani, Athanasia Amanda; Bhakri, Samsul

2017-11-01

Poly (lactic acid) (PLA) has been known as an excellent candidate for developing the future bioplastic due to its biodegradability and competitive price. However, inherent brittleness and low thermal stability of PLA have limited its applications. Considerable studies have been developed to improve the flexibility of PLA, in which blending PLA with various plasticizers has been identified as a cost-effective way to lower glass-transition temperature (Tg) and thus improve its elongation property. In this study, PLA was modified by incorporating poly(ethylene glycol) as a plasticizer with different molecular weights (M¯w 400, 1000, and 6000, called respectively as PEG 400, PEG 1000, and PEG 6000) via a solvent-casting blend method. FTIR was used for analyzing the chemical interaction while TGA and DSC measured the thermal behavior of PLA/PEG. The results indicated that the addition of lower M¯w (PEG 400 and PEG 1000) could reduce the Tg due to the enhancement of chain mobility of PLA with PEG and so driving into a more amorphous states resulted reduction of melting temperature (Tm) compared to the neat PLA. Further, at a higher M¯w of PEG 6000, the longer chain of ethylene glycol, in contrast, resulted a gradual increase in the Tg as well as Tm where the value went back to the point of neat PLA compared to the other lower molecular weight of PLA. This was due to the decrease in polymer miscibility with the increasing of M¯w. In terms of thermal stability, the addition of PEG exhibited two step degradation behavior while the neat PLA only possessed single step degradation. The presence of PEG could act as a protective barrier layer that could hinder the permeability of the volatile compound and product during decomposition reaction and thus could eventually delay and slower the degradation process. It was observed that the addition of PEG at higher M¯w (PEG1000 and PEG 6000) exhibited a higher second degradation temperature up to 380 °C.

Polyethylene Oxide (PEO) and Polyethylene Glycol (PEG) Polymer Sieving Matrix for RNA Capillary Electrophoresis

PubMed Central

Yamaguchi, Yoshinori; Li, Zhenqing; Zhu, Xifang; Liu, Chenchen; Zhang, Dawei; Dou, Xiaoming

2015-01-01

The selection of sieving polymer for RNA fragments separation by capillary electrophoresis is imperative. We investigated the separation of RNA fragments ranged from 100 to 10,000 nt in polyethylene glycol (PEG) and polyethylene oxide (PEO) solutions with different molecular weight and different concentration. We found that the separation performance of the small RNA fragments (<1000 nt) was improved with the increase of polymer concentration, whereas the separation performance for the large ones (>4000 nt) deteriorated in PEG/PEO solutions when the concentration was above 1.0%/0.6%, respectively. By double logarithmic plot of mobility and RNA fragment size, we revealed three migration regimes for RNA in PEG (300-500k) and PEO (4,000k). Moreover, we calculated the smallest resolvable nucleotide length (N min) from the resolution length analysis. PMID:25933347

Relationship between complement activation, cellular uptake and surface physicochemical aspects of novel PEG-modified nanocapsules.

PubMed

Mosqueira, V C; Legrand, P; Gulik, A; Bourdon, O; Gref, R; Labarre, D; Barratt, G

2001-11-01

The aim of our work was to examine the relationship between modifications of the surface of nanocapsules (NC) by adsorption or covalent grafting of poly(ethylene oxide) (PEG), and changes in their phospholipid (PL) content on complement activation (C3 cleavage) and on uptake by macrophages. The physicochemical characterization of the NC included an investigation of their properties, such as surface charge, size, hydrophilicity, morphology and homogeneity. This is the first time that such properties have been correlated with biological interactions for NC, a novel carrier system with a structure more complex than nanospheres. C3 crossed immunoelectrophoresis revealed the reduced activation for NC with longer PEG chain and higher density, although all formulations induced C3 cleavage to a lesser or greater extent. NC bearing PEG covalently bound to the surface were weaker activators of complement than plain PLA [poly(D,L-lactide)] NC or nanospheres (NS). Furthermore, the fluorescent/confocal microscopy of J774A1 cells in contact with NC reveal a dramatically reduced interaction with PEG-bearing NC. However, the way in which PEG was attached (covalent or adsorbed) seemed to affect the mechanism of uptake. Taken together, these results suggest that the low level of protein binding to NC covered with a high density of 20kDa PEG chains is likely to be due to the steric barriers surrounding these particles, which prevents protein adsorption and reduces their interaction with macrophages.

Galactosylated DNA lipid nanocapsules for efficient hepatocyte targeting.

PubMed

Morille, M; Passirani, C; Letrou-Bonneval, E; Benoit, J-P; Pitard, B

2009-09-11

The main objective of gene therapy via a systemic pathway is the development of a stable and non-toxic gene vector that can encapsulate and deliver foreign genetic materials into specific cell types with the transfection efficiency of viral vectors. With this objective, DNA complexed with cationic lipids of DOTAP/DOPE was encapsulated into lipid nanocapsules (LNCs) forming nanocarriers (DNA LNCs) with a size suitable for systemic injection (109+/-6 nm). With the goal of increasing systemic delivery, LNCs were stabilised with long chains of poly(ethylene glycol) (PEG), either from a PEG lipid derivative (DSPE-mPEG(2000)) or from an amphiphilic block copolymer (F108). In order to overcome internalisation difficulties encountered with PEG shield, a specific ligand (galactose) was covalently added at the distal end of the PEG chains, in order to provide active targeting of the asialoglycoprotein-receptor present on hepatocytes. This study showed that DNA LNCs were as efficient as positively charged DOTAP/DOPE lipoplexes for transfection. In primary hepatocytes, when non-galactosylated, the two polymers significantly decreased the transfection, probably by creating a barrier around the DNA LNCs. Interestingly, galactosylated F108 coated DNA LNCs led to a 18-fold increase in luciferase expression compared to non-galactosylated ones.

Amphiphilic polymer based on fluoroalkyl and PEG side chains for fouling release coating

NASA Astrophysics Data System (ADS)

Cong, W. W.; Wang, K.; Yu, X. Y.; Zhang, H. Q.; Lv, Z.; Gui, T. J.

2017-12-01

Under static conditions, fouling release coating could not express good release property to marine organisms. Amphiphilic polymer with mixture of fluorinated monomer and short side group of polyethylene glycol (PEG) was synthesized. And also we studied the ability of amphiphilic polymer to influence the surface properties and how it controlled the adhesion of marine organisms to coated surfaces. By incorporating fluorinated monomer and PEG side chain into the polymer, the effect of incorporating both polar and non-polar groups on fouling-release coating could be studied. The dry surface was characterized by three-dimensional digital microscopy and scanning electron microscopy (SEM), and the morphology of the amphiphilic fouling release coating showed just like flaky petal. The amphiphilic polymer in fouling release coating tended to reconstruct in water, and the ability was examined by static contact angle, which was smaller than the PDMS (polydimethylsiloxane) fouling release coating. Also surface energy was calculated by three solvents, and surface energy of amphiphilic fouling release coating was higher than that of the PDMS fouling release coating. To understand more about its fouling release property, seawater exposure method was adopted in gulf of Qingdao port. Fewer diatoms Navicula were found in biofilm after using amphiphilic fouling release coating. In general, coating containing both PEG and fluorinated side chain possessed certain fouling release property.

The effect of lipid monolayer in-plane rigidity on in vivo microbubble circulation persistence

PubMed Central

Garg, Sumit; Thomas, Alex A.; Borden, Mark A.

2013-01-01

The goal of this study was to increase in vivo microbubble circulation persistence for applications in medical imaging and targeted drug delivery. Our approach was to investigate the effect of lipid monolayer in-plane rigidity to reduce the rate of microbubble dissolution, while holding constant the microbubble size, concentration and surface architecture. We first estimated the impact of acyl chain length of the main diacyl phosphatidyl-choline (PC) lipid and inter-lipid distance on the cohesive surface energy and, based on these results, we hypothesized that microbubble stability and in vivo ultrasound contrast persistence would increase monotonically with increasing acyl chain length. We therefore measured microbubble in vitro stability to dilution with and without ultrasound exposure, as well as in vivo ultrasound contrast persistence. All measurements showed a sharp rise in stability between DPPC (C16:0) and DSPC (C18:0), which correlates to the wrinkling transition, which signals the onset of significant surface shear and gas permeation resistance, observed in prior single-bubble dissolution studies. Further evidence for the effect of the wrinkling transition came from an in vitro and in vivo stability comparison of microbubbles coated with pure DPPC with those of lung surfactant extract. Microbubble stability against dilution without ultrasound and in vivo ultrasound contrast persistence showed a monotonic increase with acyl chain length from DSPC to DBPC (C22:0). However, we also observed that stability dropped precipitously for all measurements on further increasing lipid acyl chain length from DBPC to DLiPC (C24:0). This result suggests that hydrophobic mismatch between the main PC lipid and the lipopolymer emulsifier, DSPE-PEG5000, may drive a less stable surface microstructure. Overall, these results support our general hypothesis of the role of in-plane rigidity for increasing the lifetime of microbubble circulation. PMID:23787108

Cooperation of Amphiphilicity and Crystallization for Regulating the Self-Assembly of Poly(ethylene glycol)-block-poly(lactic acid) Copolymers.

PubMed

Wang, Zhen; Cao, Yuanyuan; Song, Jiaqi; Xie, Zhigang; Wang, Yapei

2016-09-20

Tuning the amphiphilicity of block copolymers has been extensively exploited to manipulate the morphological transition of aggregates. The introduction of crystallizable moieties into the amphiphilic copolymers also offers increasing possibilities for regulating self-assembled structures. In this work, we demonstrate a detailed investigation of the self-assembly behavior of amphiphilic poly(ethylene glycol)-block-poly(l-lactic acid) (PEG-b-PLLA) diblock copolymers with the assistance of a common solvent in aqueous solution. With a given length of the PEG block, the molecular weight of the PLA block has great effect on the morphologies of self-assembled nanoaggregates as a result of varying molecular amphiphilicity and polymer crystallization. Common solvents including N,N-dimethylformamide, dioxane, and tetrahydrofuran involved in the early stage of self-assembly led to the change in chain configuration, which further influences the self-assembly of block copolymers. This study expanded the scope of PLA-based copolymers and proposed a possible mechanism of the sphere-to-lozenge and platelet-to-cylinder morphological transitions.

Structural relaxation processes in polyethylene glycol/CCl4 solutions by Brillouin scattering.

PubMed

Pochylski, M; Aliotta, F; Błaszczak, Z; Gapiński, J

2005-03-10

We present results of a Brillouin scattering experiment on solutions of poly(ethylene glycol) of mean molecular mass 600 g/mol (PEG600) in CCl4. The relaxation process detected has been assigned to conformational rearrangements of the polymeric chains, triggered by reorientation of the side groups. The concentration dependencies of the hypersound velocity and normalized absorption are compared against the indications from several models proposed in the literature. The concentration evolution of the system is described in terms of two distinct regimes. At high polymer content, the system is dominated by the structure of the dense polymer, where polymer-polymer interactions, together with excluded volume effects, induce the existence of a preferred local arrangement resulting in a narrow distribution of the relaxation times, with the average value of the relaxation time following a simple Arrhenius temperature dependence. As the concentration decreases, the original structure of the hydrogen bonded polymer network is destroyed, and a number of different local configuration coexist, giving rise to a wider distribution of relaxation times or to a multiple relaxation. At low concentrations, the experimental data are well fitted assuming a Vogel-Fulker-Tammon behavior for the average relaxation time. In addition, the observed deviation from the ideal behavior for the refractive index and the density suggests that CCl4 does not behave as an inert solvent, and due to polarization effects, it can develop local hetero-associated structures via electrostatic interaction with the O-H end groups of the polymeric chains. The hypothesis has been successfully tested by fitting the concentration behavior of the hypersonic velocity to a recent three-component model, suitable to describe the concentration dependence of sound velocity in moderately interacting fluids. The indication of the model furnishes a very high value for the association constant of the PEG600, confirming the literature indication that, in polymeric systems capable of developing long liner aggregates via hydrogen bonding interaction, the Brillouin probe is insensitive to the true length of the polymeric chains. The Brillouin scattering experiment just sees an effective hydrogen bonded aggregate that is huge relative to the length of the single polymeric chain and becomes sensitive only to the density fluctuations of the local segmental motions.

Hydroxypropyl-β-CD vs. its α-homologue for a 3D modified polyrotaxane network formation and properties: the relationship between modified CD and polymer revealed through comparison.

PubMed

Li, Zhao; Zheng, Zhen; Su, Shan; Yu, Lin; Wang, Xinling

2016-09-14

The threading mechanism of the hydroxypropyl-cyclodextrin (Hy-CD)/tetrahedron-like poly(ethylene glycol) (tetra-PEG) based host-guest complex and the relationship between Hy-CD and poly(ethylene oxide) (PEO) in the three-dimensional modified polyrotaxane (PR) formed by the complex were revealed through the comparison between Hy-β-CD/tetra-PEG and Hy-α-CD/tetra-PEG based systems from the macroscopic material view to the microscopic molecular view. The complexation between Hy-CD and tetra-PEG in water experiences a threading-dethreading-rethreading process which is controlled by the intermolecular interaction intensity or molecular hindrance depending on the feed ratio of Hy-CD to tetra-PEG. In the 3D modified PR, the methyl group of the Hy part on one Hy-CD can insert into the cavity of the adjacent Hy-CD and interacts with both the interior surface of the cavity and the PEO segment within the cavity if the cavity of Hy-CD is large enough. The threaded Hy-CD in the PR straightens the chain of PEO and suppresses the segment motion of the PEO. With the decrease of the cavity size of Hy-CD, the degree of suppression on the segment motion of PEO increases. Hy-CD threaded on the PEO chain can also deform when the 3D modified PR is compressed, and the degree of deformation increases with the increase of the cavity size of Hy-CD. These results of the modified CD/PEG based complex system set it apart from the unmodified CD/PEG based one, and reveal the structure-property relationship of this new type of Hy-CD/tetra-PEG based 3D modified PR material.

Modeling of hyaluronic acid containing anti-cancer drugs-loaded polylactic-co-glycolic acid bioconjugates for targeted delivery to cancer cells

NASA Astrophysics Data System (ADS)

Gul-e-Saba, Adulphakdee, A.; Madthing, A.; Zafar, M. N.; Abdullah, M. A.

2012-09-01

Molecular modeling of hyaluronan (HA), polylactic-co-glycolic acid (PLGA), polyethylene glycol-bis-amine (PEG-bis-amine), Curcumin, Cisplatin and the conjugate HA-PEG-PLGA containing Curcumin/Cisplatin were performed using Discovery Studio 2.5 to better understand issues and constraints related to targeted delivery of potent anticancer drugs to cancer cells. HA, a versatile biopolymer is a ligand of cancer cell receptor, CD44 that can be particularly useful in a receptor-mediated cellular uptake of drug-incorporated nanoparticles. Biocompatible and biodegradable polymers, PLGA and PEG, serve as polymeric micelles for controlled-release of drug. Curcumin as a natural anticancer agent has poor solubility that limits its use in drug therapeutics, while platinum-based Cisplatin exhibits systemic cytotoxicity. These can be overcome via drug delivery in polymeric biocompatible vehicles. The PLGA-PEG-HA conjugate shows the total measurement of 105 bond length with average bond length of 1.274163 Å. The conjugation between PEG and HA occurs at C8-O1 atoms and can be manipulated to improve properties.

Improving TCO-Conjugated Antibody Reactivity for Bioorthogonal Pretargeting

NASA Astrophysics Data System (ADS)

Chu, Tina Tingyi

Cancer remains a major cause of death because of its unpredictable progression. Utilizing bioorthogonal chemistry between trans-cyclooctene (TCO) and tetrazine to target imaging agents to tumors in two subsequent steps offers a more versatile platform for molecular imaging. This is accomplished by pretargeting TCO-modified primary antibody to cell surface biomarkers, followed by delivery of tetrazine-modified imaging probes. In previous work, it has been established that TCO-tetrazine chemistry can be applied to in vivo imaging, resulting in precise tumor detection. However, most TCO modifications on an antibody are not reactive because they are buried within hydrophobic domains. To expose and improve the reactivity, Rahim et al. incorporated a polyethylene glycol (PEG) linker through a two-step reaction with DBCO-azide, which successfully maintained 100% TCO functionality. In this project, various types of linkers were studied to improve the reactivity in a single step. Three primary types of linkers were studied: hydrophilic PEG chains, hydrophobic short linkers, and amphiphilic linkers. Our results show that PEG chain alone can only maintain 40% TCO reactivity. Unexpectedly, a short alkyl chain (valeric acid) provided superior results, with 60% TCO reactivity. Lengthening the alkyl chain did not improve results further. Finally, an amphiphilic linker containing valeric acid and PEG performed worse than either linker type alone, at ˜30% functionality. We conclude that our previous 100% functional TCO result obtained with the two-step coupling may have stemmed from generation of the DBCO/azide cycloaddition product. Future work will explore factors such as rigidity of linker structure, polarity, or charges.

``Sheddable'' PEG-lipid to balance the contradiction of PEGylation between long circulation and poor uptake

NASA Astrophysics Data System (ADS)

Zhao, Caiyan; Deng, Hongzhang; Xu, Jing; Li, Shuyi; Zhong, Lin; Shao, Leihou; Wu, Yan; Liang, Xing-Jie

2016-05-01

PEGylated lipids confer longer systemic circulation and tumor accumulation via the enhanced permeability and retention (EPR) effect. However, PEGylation inhibits cellular uptake and subsequent endosomal escape. In order to balance the contradiction between the advantages of long circulation and the disadvantages of poor uptake of PEGylated lipids, we prepared a ``sheddable'' PEG-lipid micelle system based on the conjugation of PEG and phosphatidyl ethanolamine (DSPE) with a pH sensitive benzoic imine bond. In a physiological environment, the PEG-protected micelles were not readily taken up by the reticuloendothelial system (RES) and could be successfully delivered to tumor tissue by the EPR effect. In a tumor acidic microenvironment, the PEG chains detached from the surfaces of the micelles while the degree of linker cleavage could not cause a significant particle size change, which facilitated the carrier binding to tumor cells and improved the cellular uptake. Subsequently, the ``sheddable'' PEG-lipid micelles easily internalized into cells and the increased acidity in the lysosomes further promoted drug release. Thus, this ``sheddable'' PEG-lipid nanocarrier could be a good candidate for effective intracellular drug delivery in cancer chemotherapy.PEGylated lipids confer longer systemic circulation and tumor accumulation via the enhanced permeability and retention (EPR) effect. However, PEGylation inhibits cellular uptake and subsequent endosomal escape. In order to balance the contradiction between the advantages of long circulation and the disadvantages of poor uptake of PEGylated lipids, we prepared a ``sheddable'' PEG-lipid micelle system based on the conjugation of PEG and phosphatidyl ethanolamine (DSPE) with a pH sensitive benzoic imine bond. In a physiological environment, the PEG-protected micelles were not readily taken up by the reticuloendothelial system (RES) and could be successfully delivered to tumor tissue by the EPR effect. In a tumor acidic microenvironment, the PEG chains detached from the surfaces of the micelles while the degree of linker cleavage could not cause a significant particle size change, which facilitated the carrier binding to tumor cells and improved the cellular uptake. Subsequently, the ``sheddable'' PEG-lipid micelles easily internalized into cells and the increased acidity in the lysosomes further promoted drug release. Thus, this ``sheddable'' PEG-lipid nanocarrier could be a good candidate for effective intracellular drug delivery in cancer chemotherapy. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr02174c

Molecular Level Investigations of Interfacial Friction of Polymer Brush Surfaces

NASA Astrophysics Data System (ADS)

Perry, Scott

2005-03-01

The development of synthetic polymer lubricants to mimic joint lubrication within the human body will be presented. Unlike most industrial applications involving oils and greases, lubrication of these joints is accomplished in an aqueous environment. Fundamentally, water is a poor lubricant in most settings due to the weak pressure dependence of its viscosity, yet the contacting surfaces of skeletal joints function with low friction throughout a lifetime. Motivated by the molecular structure of materials making up joint surfaces, interfacial friction between polymer brush surfaces under aqueous environments has been probed with an array of molecularly sensitive surface analytical techniques including atomic force microscopy. The brush surfaces, comprised of poly(L-lysine)-g-poly(ethylene glycol) (PLL-g-PEG), have been generated through the spontaneous adsorption of polymer from solution onto oxide substrates and sodium borosilicate surfaces (AFM tip). The character of the polymer films has been investigated in-situ with the quartz crystal microbalance (QCM) and atomic force microscope (AFM) and ex-situ with ellipsometry and X-ray photoelectron spectroscopy (XPS). The interfacial friction measurements have been carried out on polymer-coated substrates with bare or polymer-coated, microsphere-attached tips in over a range of solution conditions. It was found that the adsorption of polymer on oxides strikingly reduced the interfacial friction, resulting in ultra-low friction under certain conditions. By using a series of PLL-g-PEG polymers differing from each other in PEG side-chain length and grafting ratio, we observed that frictional properties of polymer-coated interfaces strongly depend on the architecture of PLL-g-PEG. Polymer-film formation and the influence of polymer architecture will be reviewed while the role of solvent and manifestation of ultra-low friction will be discussed in detail.

Promoter-Based Theranostics for Prostate Cancer

DTIC Science & Technology

2016-06-01

diagnosis vector consists of the tumor-specific PEG-promoter (PEG-Prom) and cDNA of human chorionic gonadotropin β chain (βhCG) as a reporter. We...transfection efficiency. We also used CpG-free cDNA of Figure 5. pCpGfree-PEGwt-HSV1-tk-neo vector expressed functional thymidine kinase in human

Biodistribution and pharmacokinetic analysis of long-circulating thiolated gelatin nanoparticles following systemic administration in breast cancer-bearing mice.

PubMed

Kommareddy, Sushma; Amiji, Mansoor

2007-02-01

The objective of the present study was to modify thiolated gelatin nanoparticles with poly(ethylene glycol) (PEG) chains and examine their long circulating and tumor-targeting properties in vivo in an orthotopic a human breast adenocarcinoma xenograft model. The crosslinked nanoparticle systems were characterized to have a size of 150-250 nm with rapid payload release properties in a highly reducing environment. Upon PEG modification, the nanoparticle size increased to 300-350 nm in diameter. The presence of PEG chains on the surface was confirmed by characterization with electron spectroscopy for chemical analysis. The in vivo long-circulating potential, biodistribution and passive tumor targeting of the controls, and PEG-modified thiolated gelatin nanoparticles were evaluated by injecting indium-111 (111In)-labeled nanoparticles into breast tumor (MDA-MB-435)-bearing nude mice. Upon modification with PEG, the nanoparticles were found to have longer circulation times, with the plasma and tumor half-lives of 15.3 and 37.8 h, respectively. The results also showed preferential localization of thiolated nanoparticles in the tumor mass. The resulting nanoparticulate systems with long circulation properties could be used to target encapsulated drugs and genes to tumors passively by utilizing the enhanced permeability and retention effect of the tumor vasculature. Copyright (c) 2006 Wiley-Liss, Inc.

Controlled Thermoresponsive Hydrogels by Stereocomplexed PLA-PEG-PLA Prepared via Hybrid Micelles of Pre-Mixed Copolymers with Different PEG Lengths

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abebe, Daniel G.; Fujiwara, Tomoko

2012-09-05

The stereocomplexed hydrogels derived from the micelle mixture of two enantiomeric triblock copolymers, PLLA-PEG-PLLA and PDLA-PEG-PDLA, reported in 2001 exhibited sol-to-gel transition at approximately body temperature upon heating. However, the showed poor storage modulus (ca. 1000 Pa) determined their insufficiency as injectable implant biomaterials for many applications. In this study, the mechanical property of these hydrogels was significantly improved by the modifications of molecular weights and micelle structure. Co-micelles composed of block copolymers with two sizes of PEG block length were shown to possess unique and dissimilar properties from the micelles composed of single-sized block copolymers. The stereomixture of PLA-PEG-PLAmore » comicelles showed a controllable sol-to-gel transition at a wide temperature range of 4 and 80 C. The sol-gel phase diagram displays a linear relationship of temperature versus copolymer composition; hence, a transition at body temperature can be readily achieved by adjusting the mixed copolymer ratio. The resulting thermoresponsive hydrogels exhibit a storage modulus notably higher (ca. 6000 Pa) than that of previously reported hydrogels. As a physical network solely governed by self-reorganization of micelles, followed by stereocomplexation, this unique system offers practical, safe, and simple implantable biomaterials.« less

Polyethylene Glycol Based Graphene Aerogel Confined Phase Change Materials with High Thermal Stability.

PubMed

Fu, Yang; Xiong, Weilai; Wang, Jianying; Li, Jinghua; Mei, Tao; Wang, Xianbao

2018-05-01

Polyethylene glycol (PEG) based graphene aerogel (GA) confined shaped-stabilized phase change materials (PCMs) are simply prepared by a one-step hydrothermal method. Three-dimensional GA inserted by PEG molecule chains, as a supporting material, obtained by reducing graphene oxide sheets, is used to keep their stabilized shape during a phase change process. The volume of GA is obviously expended after adding PEG, and only 9.8 wt% of GA make the composite achieve high energy efficiency without leakage during their phase change because of hydrogen bonding widely existing in the GA/PEG composites (GA-PCMs). The heat storage energy of GA-PCMs is 164.9 J/g, which is 90.2% of the phase change enthalpy of pure PEG. In addition, this composite inherits the natural thermal properties of graphene and thus shows enhanced thermal conductivity compared with pure PEG. This novel study provides an efficient way to fabricate shape-stabilized PCMs with a high content of PEG for thermal energy storage.

Novel Bioconjugation Strategy Using Elevated Hydrostatic Pressure: A Case Study for the Site-Specific Attachment of Polyethylene Glycol (PEGylation) of Recombinant Human Ciliary Neurotrophic Factor.

PubMed

Wang, Qi; Zhang, Chun; Guo, Fangxia; Li, Zenglan; Liu, Yongdong; Su, Zhiguo

2017-11-15

In this paper, we reported a novel strategy for the site-specific attachment of polyethylene glycol (PEGylation) of proteins using elevated hydrostatic pressure. The process was similar to the conventional one except the reactor was under elevated hydrostatic pressure. The model protein was recombinant human ciliary neurotrophic factor (rhCNTF), and the reagent was monomethoxy-polyethylene glycol-maleimide (mPEG-MAL). PEGylation with mPEG (40 kDa)-MAL at pH 7.0 under normal pressure for 5 h achieved a less than 5% yield. In comparison, when the pressure was elevated, the PEGylation yield was increased dramatically, reaching nearly 90% at 250 MPa. Furthermore, the following phenomena were observed: (1) high-hydrostatic-pressure PEGylation (HHPP) could operate at a low reactant ratio of 1:1.2 (rhCNTF to mPEG-MAL), while the conventional process needs a much-higher ratio. (2) Short and long chains of PEG gave a similar yield of 90% in HHPP, while the conventional yield for the short chain of the PEG was higher than that of the long chain. (3) The reaction pH in the range of 7.0 to 8.0 had almost no influence upon the yield of HHPP, while the PEGylation yield was significantly increased by a factor of three from pH 7.0 to 8.0 at normal pressure. Surface accessibility analysis was performed using GRASP2 software, and we found that Cys17 of rhCNTF was located at the concave patches, which may have steric hindrance for the PEG to approach. The speculated benefit of HHPP was the facilitation of target-site exposure, reducing the steric hindrance and making the reaction much easier. Structure and activity analysis demonstrated that the HHPP product was comparable to the PEGylated rhCNTF prepared through a conventional method. Overall, this work demonstrated that HHPP, as we proposed, may have application potentials in various conjugations of biomacromolecules.

Ligand conjugation to bimodal poly(ethylene glycol) brush layers on microbubbles.

PubMed

Chen, Cherry C; Borden, Mark A

2010-08-17

Using microbubbles as model systems, we examined molecular diffusion and binding to colloidal surfaces in bimodal poly(ethylene glycol) (PEG) brush layers. A microbubble is a gaseous colloidal particle with a diameter of less than 10 mum, of which the surface comprises amphiphilic phospholipids self-assembled to form a lipid monolayer shell. Due to the compressible gas core, microbubbles provide a sensitive acoustic response and are currently used as ultrasound contrast agents. Similar to the design of long circulating liposomes, PEG chains are typically incorporated into the shell of microbubbles to form a steric barrier against coalescence and adsorption of macromolecules to the microbubble surface. We introduced a buried-ligand architecture (BLA) design where the microbubble surface was coated with a bimodal PEG brush. After microbubbles were generated, fluorescent ligands with different molecular weights were conjugated to the tethered functional groups on the shorter PEG chains, while the longer PEG chains served as a shield to protect these ligands from exposure to the surrounding environment. BLA microbubbles reduced the binding of macromolecules (>10 kDa) to the tethers due to the steric hindrance of the PEG overbrush while allowing the uninhibited attachment of small molecules (<1 kDa). Roughly 40% less fluorescein-conjugated streptavidin (SA-FITC) bound to BLA microbubbles compared to exposed-ligand architecture (ELA) microbubbles. The binding of SA-FITC to BLA microbubbles suggested a possible phase separation between the lipid species on the surface leading to populations of revealed and concealed ligands. Ligand conjugation kinetics was independent of microbubble size, regardless of ligand size or microbubble architecture. We observed, for the first time, streptavidin-induced surface structure formation for ELA microbubbles and proposed that this phenomenon may be correlated to flow cytometry scattering measurements. We therefore demonstrated the feasibility of postlabeling for small-molecule ligands to BLA microbubbles to generate stealth targeted ultrasound contrast agents.

Physicochemical Parameters Affecting the Electrospray Ionization Efficiency of Amino Acids after Acylation

PubMed Central

2017-01-01

Electrospray ionization (ESI) is widely used in liquid chromatography coupled to mass spectrometry (LC–MS) for the analysis of biomolecules. However, the ESI process is still not completely understood, and it is often a matter of trial and error to enhance ESI efficiency and, hence, the response of a given set of compounds. In this work we performed a systematic study of the ESI response of 14 amino acids that were acylated with organic acid anhydrides of increasing chain length and with poly(ethylene glycol) (PEG) changing certain physicochemical properties in a predictable manner. By comparing the ESI response of 70 derivatives, we found that there was a strong correlation between the calculated molecular volume and the ESI response, while correlation with hydrophobicity (log P values), pKa, and the inverse calculated surface tension was significantly lower although still present, especially for individual derivatized amino acids with increasing acyl chain lengths. Acylation with PEG containing five ethylene glycol units led to the largest gain in ESI response. This response was maximal independent of the calculated physicochemical properties or the type of amino acid. Since no actual physicochemical data is available for most derivatized compounds, the responses were also used as input for a quantitative structure–property relationship (QSPR) model to find the best physicochemical descriptors relating to the ESI response from molecular structures using the amino acids and their derivatives as a reference set. A topological descriptor related to molecular size (SPAN) was isolated next to a descriptor related to the atomic composition and structural groups (BIC0). The validity of the model was checked with a test set of 43 additional compounds that were unrelated to amino acids. While prediction was generally good (R2 > 0.9), compounds containing halogen atoms or nitro groups gave a lower predicted ESI response. PMID:28737384

Facile controlled synthesis of micro/nanostructure MCrO 4 (M = Ba, Pb) by using Gemini surfactant C 12-PEG-C 12 as a soft template

NASA Astrophysics Data System (ADS)

Chang, Wengui; Shen, Yuhua; Xie, Anjian; Liu, Xue

2010-04-01

Gemini surfactants, double sodium α-sulfonic polyethylene glycol laurate (abbreviated C 12-PEG-C 12), were prepared and applied as soft templates in the controlled synthesis of BaCrO 4 and PbCrO 4 micro/nanocrystals. The template effects were investigated by adjusting the length of the spacer, using PEG400 and PEG4000, of the Gemini surfactant. The results indicated that the size and morphology of BaCrO 4 and PbCrO 4 micro/nanocrystals varied with the change in spacer length of C 12-PEG-C 12, suggesting that the different lengths of the polyethylene glycol group spacers in the Gemini surfactants played a key role in determining the size and shape of the MCrO 4 micro/nanoparticles. The dynamic process of the formation of the novel morphology BaCrO 4 crystals showed that the morphology grew from a round-bar polyhedron, to regular polyhedron, to approximate octahedron to a uniform pistachio nut shape. The growth mechanism of the BaCrO 4 micro/nanocrystals was explained that C 12-PEG-C 12 had a greater interfacial adsorption and would effectively control the shape evolution during the crystal growth, while PbCrO 4 could be explained that the Gemini surfactants can undergo liquid-crystalline phase transitions with long channels providing a soft template effect and derived the nanorods formation. Room temperature fluorescence spectra were studied and these showed that the pistachio-shaped BaCrO 4 microcrystals and PbCrO 4 nanorods possess photoactive luminescence properties with emission peaks at 470 and 549 nm, respectively.

Distraction induced enterogenesis: a unique mouse model using polyethylene glycol.

PubMed

Okawada, Manabu; Maria, Haytham Mustafa; Teitelbaum, Daniel H

2011-09-01

Recent studies have demonstrated that the small intestine can be lengthened by applying mechanical forces to the bowel lumen-distraction-induced enterogenesis. However, the mechanisms which account for this growth are unknown, and might be best examined using a mouse model. The purpose of this study is to establish the feasibility of developing distractive-induced small bowel growth in mouse. Twelve-week old C57BL/6J mice had a jejunal segment taken out of continuity, and distended with polyethylene glycol (PEG: 3350 KDa); this group was compared with a control group without stretching. Segment length and diameter were measured intra-operatively and after 5 d. Villus height, crypt depth, and muscle thickness in the isolated segment were assessed. Rate of epithelial cell proliferation (5-bromo-2-deoxyuridine: BrdU incorporation) in crypts were also examined. The mucosal mRNA expression of targeted factors was performed to investigate potential mechanisms which might lead to distraction-induced enterogenesis. At harvest, the PEG-stretched group showed a significant increase in length and diameter versus controls. Villus height, crypt depth, and muscular layer thickness increased in the PEG group. The PEG group also showed significantly increased rates of epithelial cell proliferation versus controls. Real-time PCR showed a trend toward higher β-catenin and c-myc mRNA expression in the PEG-stretched group; however, this difference was not statistically significant. Radial distraction-induced enterogenesis with PEG is a viable method for increasing small intestinal length and diameter. This model may provide a new method for studying the mechanisms leading to distraction-induced enterogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.

Hyaluronic Acid Hydrogel Functionalized with Self-Assembled Micelles of Amphiphilic PEGylated Kartogenin for the Treatment of Osteoarthritis.

PubMed

Kang, Mi-Lan; Jeong, Se-Young; Im, Gun-Il

2017-07-01

Synthetic hyaluronic acid (HA) containing a covalently integrated drug is capable of releasing therapeutic molecules and is an attractive candidate for the intra-articular treatment of osteoarthritis (OA). Herein, self-assembled PEGylated kartogenin (PEG/KGN) micelles consisting of hydrophilic polyethylene glycol (PEG) and hydrophobic KGN, which has been shown to induce chondrogenesis in human mesenchymal stem cells, were prepared by covalent crosslinking. HA hydrogels containing PEG/KGN micelles (HA/PEG/KGN) were prepared by covalently bonding PEG chains to HA. The physicochemical properties of the HA/PEG/KGN conjugate gels were investigated using Fourier transform infrared spectroscopy, 1 H NMR, dynamic light scattering (DLS), and scanning electron microscopy (SEM). HA/PEG/KGN gels exhibited larger micelles in aqueous solution than PEG/KGN. SEM images of PEG/KGN micelles showed a dark core and a bright shell, whereas PEG/KGN micelles covalently integrated into HA had an irregular oval shape. Covalent integration of PEG/KGN micelles in HA hydrogels significantly reduced drug release rates and provided sustained release over a prolonged period of time. HA/PEG/KGN hydrogels were degradable enzymatically by collagenase and hyaluronidase in vitro. Injection of HA/PEG/KGN hydrogels into articular cartilage significantly suppressed the progression of OA in rats compared with free-HA hydrogel injection. These results suggest that the HA/PEG/KGN hydrogels have greater potency than free-HA hydrogels against OA as biodegradable synthetic therapeutics.

Compartmentalization Technologies via Self-Assembly and Cross-Linking of Amphiphilic Random Block Copolymers in Water.

PubMed

Matsumoto, Mayuko; Terashima, Takaya; Matsumoto, Kazuma; Takenaka, Mikihito; Sawamoto, Mitsuo

2017-05-31

Orthogonal self-assembly and intramolecular cross-linking of amphiphilic random block copolymers in water afforded an approach to tailor-make well-defined compartments and domains in single polymer chains and nanoaggregates. For a double compartment single-chain polymer, an amphiphilic random block copolymer bearing hydrophilic poly(ethylene glycol) (PEG) and hydrophobic dodecyl, benzyl, and olefin pendants was synthesized by living radical polymerization (LRP) and postfunctionalization; the dodecyl and benzyl units were incorporated into the different block segments, whereas PEG pendants were statistically attached along a chain. The copolymer self-folded via the orthogonal self-assembly of hydrophobic dodecyl and benzyl pendants in water, followed by intramolecular cross-linking, to form a single-chain polymer carrying double yet distinct hydrophobic nanocompartments. A single-chain cross-linked polymer with a chlorine terminal served as a globular macroinitiator for LRP to provide an amphiphilic tadpole macromolecule comprising a hydrophilic nanoparticle and a hydrophobic polymer tail; the tadpole thus self-assembled into multicompartment aggregates in water.

High-efficiency Gaussian key reconciliation in continuous variable quantum key distribution

NASA Astrophysics Data System (ADS)

Bai, ZengLiang; Wang, XuYang; Yang, ShenShen; Li, YongMin

2016-01-01

Efficient reconciliation is a crucial step in continuous variable quantum key distribution. The progressive-edge-growth (PEG) algorithm is an efficient method to construct relatively short block length low-density parity-check (LDPC) codes. The qua-sicyclic construction method can extend short block length codes and further eliminate the shortest cycle. In this paper, by combining the PEG algorithm and qua-si-cyclic construction method, we design long block length irregular LDPC codes with high error-correcting capacity. Based on these LDPC codes, we achieve high-efficiency Gaussian key reconciliation with slice recon-ciliation based on multilevel coding/multistage decoding with an efficiency of 93.7%.

Effect of Ca2+ ion concentration on adsorption of poly(carboxylate ether)-based (PCE) superplasticizer on mica.

PubMed

Wu, Bo; Chun, Byong-Wa; Gu, Le; Kuhl, Tonya L

2018-05-09

Poly(carboxylate ether)-based (PCE) superplasticizers consist of a carboxylic acid backbone and grafted poly(ethylene glycol) (PEG) side chains. Ca 2+ ion bridging mechanism is commonly purported to control PCE's adsorption on negatively charged cement particle surfaces in cement suspension, thus PCE was expected to adsorb on negatively charged surfaces in synthetic pore solutions via Ca 2+ /COO - interactions. Adsorption behaviors of a commercial PCE on negatively charged mica were studied in aqueous electrolyte solutions by a surface forces apparatus. Direct force measurements indicated that the PCE adsorbed onto mica from 0.1 M K 2 SO 4 due to K + ion chelation by the ether oxygen units CH 2 CH 2 O on the PEG chains, but surprisingly did not adsorb from either 0.1 M K 2 SO 4 with saturated Ca(OH) 2 or 0.1 M Ca(NO 3 ) 2 . The adsorption in K 2 SO 4 was weak, enabling the adsorbed PCE layers to be squeezed out under modest compression. Upon separating the surfaces, the PCE immediately achieved an identical re-adsorption. In high-calcium conditions, the PCE was highly positively charged due to Ca 2+ ion chelation by PEG chains and backbone carboxylic groups COO - , and mica also underwent charge reversal due to electrostatic adsorption/binding of Ca 2+ ions. Consequently, the interaction between mica and PCE was electrostatically repulsive and no PCE adsorption occurred. These findings can be explained by the complex interplay of ion chelation by PEG chains, electrostatic binding and screening interactions with charged surfaces in the presence of monovalent and divalent counterions, and ultimately charge reversal of both the charged surfaces and polyelectrolyte in high divalent ion conditions. Copyright © 2018 Elsevier Inc. All rights reserved.

Formation and evolution of anodic TiO2 nanotube embryos

NASA Astrophysics Data System (ADS)

Jin, Rong; Liao, Maoying; Lin, Tong; Zhang, Shaoyu; Shen, Xiaoping; Song, Ye; Zhu, Xufei

2017-06-01

Anodic TiO2 nanotubes (ATNTs) have been widely investigated for decades due to their interesting nanostructures and various applications. However, the formation mechanism of ATNTs still remains unclear. To date, most of researches focus on the tubular structure but neglect the formation process of initial nanotube embryos. Herein, polyethylene glycol (PEG) is added into the traditional electrolyte to moderate the transformation process from compact layer to porous layer. Based on ‘oxygen bubble mould’ and ‘plastic flow model’ theory, the formation and evolution process of nanotube embryo is clarified firstly. Results validate the effect of ‘oxygen bubble mould’ on the formation of nanotube embryo, which has a great effect on regulating the morphology of ATNT arrays. Besides, nanotubes prepared in electrolytes with PEG show shorter tube length with larger diameter than that prepared in traditional electrolytes. The addition of PEG can also effectively avoid the breakdown phenomenon. Highlights Transformation from compact layer into porous layer is observed in PEG electrolyte. The effect of oxygen bubble mould is first demonstrated and observed. The formation process of TiO2 nanotube embryo is described systematically. TiO2 nanotubes prepared in PEG electrolyte show short length and large diameter.

Method for Impeding Degradation of Porous Silicon Structures

NASA Technical Reports Server (NTRS)

Vilentchouk, Biana Godin; Ferrari, Mauro

2011-01-01

This invention relates to surface modification of porosified silicon (pSi) structures with poly(alkylene) glycols for the purpose of controlled degradation of the silicon matrix and tailored release of encapsulated substances for biomedical applications. The pSi structures are currently used in diverse biomedical applications including bio-molecular screening, optical bio-sensoring, and drug delivery by means of injectable/orally administered carriers and implantable devices. The size of the pores and the surface chemistry of the pSi structure can be controlled during the microfabrication process and thereafter. A fine regulation of the degradation kinetics of mesoporous silicon structures is of fundamental importance. Polyethylene glycols (PEGs) represent the major category of surface modifying agents used in classical drug delivery systems and in pharmaceutical dosage forms. PEGylation enables avoidance of RES uptake, thus prolonging circulation time of intravenously injectable nanovectors. PEG molecules demonstrate little toxicity and immunogenicity, and are cleared from the body through the urine (molecular weight, MW less than 30 kDa) or in the feces (MW greater than 30kDa). The invention focuses on the possibility of finely tuning the degradation kinetics of the pSi nanovectors and other structures through surface conjugation of PEGs with various backbone lengths/MWs. To prove the concept, pSi nanovectors were covalently conjugated to seven PEGs with MW from 245 to 5,000 Da and their degradation kinetics in physiologically relevant media (phosphate buffer saline, PBS pH7.4, and fetal bovine serum) was assessed by the elemental analysis of the Si using inductive coupled plasma atomic emission spectroscopy (ICP-AES). The conjugation of the PEG with lowest MW to the nanovectors surface did not induce any change in the degradation kinetics in serum, but inhibited degradation and consequently the release of orthosilicic acid into buffer. When PEGs with the longer chains were evaluated, Si mass loss from the nanovectors was slowed down, and the PEGylated structures were almost fully degraded within 18 24 hours in serum and within 48 hours in PBS. The most dramatic effect was observed for high MW PEGs 3,400 and 5,000 Da, which prominently inhibited the degradation of the systems, with complete degradation achieved only after four days. For these PEGs, during the early stages of the degradation, there was a lag period of little or no Si mass loss from the nanovector. The obtained profiles were in agreement with the erosion of the nanovector surface as observed by scanning electron microscopy.

PEGylation of Biopharmaceuticals: A Review of Chemistry and Nonclinical Safety Information of Approved Drugs.

PubMed

Turecek, Peter L; Bossard, Mary J; Schoetens, Freddy; Ivens, Inge A

2016-02-01

Modification of biopharmaceutical molecules by covalent conjugation of polyethylene glycol (PEG) molecules is known to enhance pharmacologic and pharmaceutical properties of proteins and other large molecules and has been used successfully in 12 approved drugs. Both linear and branched-chain PEG reagents with molecular sizes of up to 40 kDa have been used with a variety of different PEG derivatives with different linker chemistries. This review describes the properties of PEG itself, the history and evolution of PEGylation chemistry, and provides examples of PEGylated drugs with an established medical history. A trend toward the use of complex PEG architectures and larger PEG polymers, but with very pure and well-characterized PEG reagents is described. Nonclinical toxicology findings related to PEG in approved PEGylated biopharmaceuticals are summarized. The effect attributed to the PEG part of the molecules as observed in 5 of the 12 marketed products was cellular vacuolation seen microscopically mainly in phagocytic cells which is likely related to their biological function to absorb and remove particles and macromolecules from blood and tissues. Experience with marketed PEGylated products indicates that adverse effects in toxicology studies are usually related to the active part of the drug but not to the PEG moiety. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Insight into fast ion migration kinetics of a new hybrid single Li-ion conductor based on aluminate complexes for solid-state Li-ion batteries.

PubMed

Feng, Yancong; Tan, Rui; Zhao, Yan; Gao, Rongtan; Yang, Luyi; Yang, Jinlong; Li, Hao; Zhou, Guofu; Chen, Haibiao; Pan, Feng

2018-03-29

A novel hybrid single Li-ion conductor (SLIC) for a Li-ion solid electrolyte was prepared by mixing aluminate complexes-polyethylene glycol (LiAl-PEG) and polyethylene oxide (PEO) for solid-state Li-ion batteries. The LiAl-PEG/PEO blend possesses high thermal stability and electrochemical stability with an oxidation decomposition voltage up to 4.8 V. Notably, this hybrid SLIC exhibits not only excellent Li-ion migration kinetics, but also good ionic conductivity as high as 4.0 × 10-5 and 2.6 × 10-4 S cm-1 at 30 and 100 °C, respectively, which is much higher than previously reported SLICs. Importantly, by the combination of molecular dynamics simulations and experiment measurements, the mechanisms of Li-ion migration across the SLIC (LiAl-PEG), the salt-in-polymer (LiClO4/PEO) and the optimized SLIC (LiAl-PEG/PEO) were systematically investigated for the first time. The new hopping transport mechanism was verified for the SLIC system at the nanoscale. As for the hybrid SLIC, PEO chains enhance the segmental mobility of the ether-chains bonded with Al atoms, improve the ionicity, and provide extra ionic paths for Li transfer, resulting in the optimized Li-ion migration kinetics of LiAl-PEG/PEO.

Enhanced Aqueous Solubility of Long Wavelength Voltage-Sensitive Dyes by Covalent Attachment of Polyethylene Glycol

PubMed Central

Patrick, Michael J.; Ernst, Lauren A.; Waggoner, Alan S.; Thai, Dung; Salama, Guy

2011-01-01

Long wavelength voltage-sensitive dyes (VSDs) called Pittsburgh (PGH) dyes were recently synthesized by coupling various heterocyclic groups to a styryl-thiophene intermediate forming extended, partially rigidized chromophores. Unlike most styryl VSDs, dyes with a sulfonic acid anchor directly attached to the chromophore showed no solvatochromic absorption shifts. The limited water solubility of many long wavelength VSDs requires the use of surfactants to transport the dye through aqueous media and effectively label biological membranes. Here, we tested the chemical substitution of the sulfonic acid moiety with polyethyleneglycol (PEG) chains ranging from MW 750 to 5000, to overcome the poor solubility of VSDs while retaining their properties as VSDs. The chemical synthesis of PGH dyes and their PEG derivatives are described. The PEG-derivatives were soluble in aqueous solutions (> 1 mM) and still reported membrane potential changes. In frog and mouse hearts, the voltage sensitivity (ΔF/F per action potential) and spectral properties of PEG dyes were the same as the sulfonated analogs. Thus, the solubility of VSDs can be considerably improved with small polyethyleneglycol chains and can provide an effective approach to improve staining of excitable tissues and optical recordings of membrane potential. PMID:17912389

Rheological and thermal properties of polylactide/silicate nanocomposites films.

PubMed

Ahmed, Jasim; Varshney, Sunil K; Auras, Rafeal

2010-03-01

Polylactide (DL)/polyethylene glycol/silicate nanocomposite blended biodegradable films have been prepared by solvent casting method. Rheological and thermal properties were investigated for both neat amorphous polylactide (PLA-DL form) and blend of montmorillonite (clay) and poly (ethylene glycol) (PEG). Melt rheology of the PLA individually and blends (PLA/clay; PLA/PEG; PLA/PEG/clay) were performed by small amplitude oscillation shear (SAOS) measurement. Individually, PLA showed an improvement in the viscoelastic properties in the temperature range from 180 to 190 degrees C. Incorporation of nanoclay (3% to 9% wt) was attributed by significant improvements in the elastic modulus (G') of PLA/clay blend due to intercalation at higher temperature. Both dynamic modulii of PLA/PEG blend were significantly reduced with addition of 10% PEG. Rheometric measurement could not be conducted while PLA/PEG blends containing 25% PEG. A blend of PLA/PEG/clay (68/23/9) showed liquid-like properties with excellent flexibility. Thermal analysis of different clay loading films indicated that the glass transition temperatures (T(g)) remained unaffected irrespective of clay concentration due to immobilization of polymer chain in the clay nanocomposite. PEG incorporation reduced the T(g) of the blend (PLA/PEG and PLA/PEG/clay) significantly. Both rheological and thermal analysis data supported plasticization and flexibility of the blended films. It is also interesting to study competition between PLA and PEG for the intercalation into the interlayer spacing of the clay. This study indicates that PLA/montmorillonite blend could serve as effective nano-composite for packaging and other applications.

Role of oxygen functional groups in reduced graphene oxide for lubrication

PubMed Central

Gupta, Bhavana; Kumar, Niranjan; Panda, Kalpataru; Kanan, Vigneshwaran; Joshi, Shailesh; Visoly-Fisher, Iris

2017-01-01

Functionalized and fully characterized graphene-based lubricant additives are potential 2D materials for energy-efficient tribological applications in machine elements, especially at macroscopic contacts. Two different reduced graphene oxide (rGO) derivatives, terminated by hydroxyl and epoxy-hydroxyl groups, were prepared and blended with two different molecular weights of polyethylene glycol (PEG) for tribological investigation. Epoxy-hydroxyl-terminated rGO dispersed in PEG showed significantly smaller values of the friction coefficient. In this condition, PEG chains intercalate between the functionalized graphene sheets, and shear can take place between the PEG and rGO sheets. However, the friction coefficient was unaffected when hydroxyl-terminated rGO was coupled with PEG. This can be explained by the strong coupling between graphene sheets through hydroxyl units, causing the interaction of PEG with the rGO to be non- effective for lubrication. On the other hand, antiwear properties of hydroxyl-terminated rGO were significantly enhanced compared to epoxy-hydroxyl functionalized rGO due to the integrity of graphene sheet clusters. PMID:28344337

Clicked bis-PEG-peptide conjugates for studying calmodulin-Kv7.2 channel binding.

PubMed

Bonache, M Angeles; Alaimo, Alessandro; Malo, Covadonga; Millet, Oscar; Villarroel, Alvaro; González-Muñiz, Rosario

2014-11-28

The recombinant Kv7.2 calmodulin (CaM) binding site (Q2AB CaMBD) shows a high tendency to aggregate, thus complicating biochemical and structural studies. To facilitate these studies we have conceived bis-PEG-peptide CaMBD-mimetics linking helices A and B in single, easy to handle molecules. Short PEG chains were selected as spacers between the two peptide molecules, and a Cu(i)-catalyzed cycloaddition (CuAAC) protocol was used to assemble the final bis-PEG-peptide conjugate, by the convenient functionalization of PEG arms with azide and alkyne groups. The resulting conjugates, with a certain helical character in TFE solutions (CD), showed nanomolar affinity in a fluorescence CaM binding in vitro assay, higher than just the sum of the precursor PEG-peptide affinities, thus validating our design. The approach to these first described examples of Kv7.2 CaMBD-mimetics could pave the way to chimeric conjugates merging helices A and B from different Kv7 subunits.

Self-assembly of core-polyethylene glycol-lipid shell (CPLS) nanoparticles and their potential as drug delivery vehicles.

PubMed

Shen, Zhiqiang; Loe, David T; Awino, Joseph K; Kröger, Martin; Rouge, Jessica L; Li, Ying

2016-08-21

Herein a new multifunctional formulation, referred to as a core-polyethylene glycol-lipid shell (CPLS) nanoparticle, has been proposed and studied in silico via large scale coarse-grained molecular dynamics simulations. A PEGylated core with surface tethered polyethylene glycol (PEG) chains is used as the starting configuration, where the free ends of the PEG chains are covalently bonded with lipid molecules (lipid heads). A complete lipid bilayer is formed at the surface of the PEGylated particle core upon addition of free lipids, driven by the hydrophobic properties of the lipid tails, leading to the formation of a CPLS nanoparticle. The self-assembly process is found to be sensitive to the grafting density and molecular weight of the tethered PEG chains, as well as the amount of free lipids added. At low grafting densities the assembly of CPLS nanoparticles cannot be accomplished. As demonstrated by simulations, a lipid bud/vesicle can be formed on the surface when an excess amount of free lipids is added at high grafting density. Therefore, the CPLS nanoparticles can only be formed under appropriate conditions of both PEG and free lipids. The CPLS nanoparticle has been recognized to be able to store a large quantity of water molecules, particularly with high molecular weight of PEG chains, indicating its capacity for carrying hydrophilic molecules such as therapeutic biomolecules or imaging agents. Under identical size and surface chemistry conditions of a liposome, it has been observed that the CPLS particle can be more efficiently wrapped by the lipid membrane, indicating its potential for a greater efficiency in delivering its hydrophilic cargo. As a proof-of-concept, the experimental realization of CPLS nanoparticles is explicitly demonstrated in this study. To test the capacity of the CPLS to store small molecule cargo a hydrophilic dye was successfully encapsulated in the particles' water soluble layer. The results of this study show the power and potential of simulation-driven approaches for guiding the design of more efficient nanomaterial delivery platforms.

Optimization of cell receptor-specific targeting through multivalent surface decoration of polymeric nanocarriers

PubMed Central

D’Addio, Suzanne M.; Baldassano, Steven; Shi, Lei; Cheung, Lila; Adamson, Douglas H.; Bruzek, Matthew; Anthony, John E.; Laskin, Debra L.; Sinko, Patrick J.; Prud’homme, Robert K.

2013-01-01

Treatment of tuberculosis is impaired by poor drug bioavailability, systemic side effects, patient non-compliance, and pathogen resistance to existing therapies. The mannose receptor (MR) is known to be involved in the recognition and internalization of Mycobacterium tuberculosis. We present a new assembly process to produce nanocarriers with variable surface densities of mannose targeting ligands in a single step, using kinetically-controlled, block copolymer-directed assembly. Nanocarrier association with murine macrophage J774 cells expressing the MR is examined as a function of incubation time and temperature, nanocarrier size, dose, and PEG corona properties. Amphiphilic diblock copolymers are prepared with terminal hydroxyl, methoxy, or mannoside functionality and incorporated into nanocarrier formulations at specific ratios by Flash NanoPrecipitation. Association of nanocarriers protected by a hydroxyl-terminated PEG corona with J774 cells is size dependent, while nanocarriers with methoxy-terminated PEG coronas do not associate with cells, regardless of size. Specific targeting of the MR is investigated using nanocarriers having 0-75% mannoside-terminated PEG chains in the PEG corona. This is a wider range of mannose densities than has been previously studied. Maximum nanocarrier association is attained with 9% mannoside-terminated PEG chains, increasing uptake more than 3-fold compared to non-targeted nanocarriers with a 5 kg mol−1 methoxy-terminated PEG corona. While a 5 kg mol−1 methoxy-terminated PEG corona prevents non-specific uptake, a 1.8 kg mol−1 methoxy-terminated PEG corona does not sufficiently protect the nanocarriers from nonspecific association. There is continuous uptake of MR-targeted nanocarriers at 37°C, but a saturation of association at 4°C. The majority of targeted nanocarriers associate with J774E cells are internalized at 37°C and uptake is receptor-dependent, diminishing with competitive inhibition by dextran. This characterization of nanocarrier uptake and targeting provides promise for optimizing drug delivery to macrophages for TB treatment and establishes a general route for optimizing targeted formulations of nanocarriers for specific delivery at targeted sites. PMID:23419950

Synthesis of a novel biomedical poly(ester urethane) based on aliphatic uniform-size diisocyanate and the blood compatibility of PEG-grafted surfaces.

PubMed

Liu, Xiaolong; Xia, Yiran; Liu, Lulu; Zhang, Dongmei; Hou, Zhaosheng

2018-05-01

The purpose of this study is to offer a novel kind of polyurethane with improved surface blood compatibility for long-term implant biomaterials. In this work, the aliphatic poly(ester-urethane) (PEU) with uniform-size hard segments was prepared and the PEU surface was grafted with hydrophilic poly(ethylene glycol) (PEG). The PEU was obtained by chain-extension of poly(ɛ-caprolactone) (PCL) with isocyanate-terminated urethane triblock. Free amino groups were introduced onto the surface of PEU film via aminolysis with hexamethylenediamine, and then the NH 2 -grafted PEU surfaces (PEU-NH 2 ) were reacted with isocyanate-terminated monomethoxyl PEG (MPEG-NCO) to obtain the PEG-grafted PEU surfaces (PEU-PEG). Analysis by nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, and gel permeation chromatography were performed to confirm the chemical structures of the chain extender, PCL, PEU, and PEU-PEG. Additionally, the influence of aminolysis on the physical-mechanical properties of PEU films was investigated. Two glass transition temperatures and a broad endothermic peak were observed in the differential scanning calorimetry curves of PEU, which demonstrated a microphase-separated and semicrystalline structure, respectively. The PEU-PEG film exhibited excellent mechanical properties with an ultimate stress of ∼39 MPa and an elongation at break of ∼1190%, which was slightly lower than that of PEU, indicating that the aminolysis has little influence on the tensile properties. Evaluation of the blood compatibility of the films by bovine serum albumin adsorption and the platelet adhesion test revealed that the PEG-grafted surface had improved resistance to protein adsorption and excellent resistance to platelet adhesion. In vitro degradation tests showed that the PEU-PEG film could maintain its mechanical properties for more than six months and only lost ∼25% weight after 18 months. Due to the excellent mechanical properties, good blood compatibility and slow degradability, this novel kind of polyurethane hold significant promise for long-term implant biomaterials, especially soft tissue augmentation and regeneration.

Steric and electrostatic surface forces on sulfonated PEG graft surfaces with selective albumin adsorption.

PubMed

Bremmell, Kristen E; Britcher, Leanne; Griesser, Hans J

2013-06-01

Addition of ionized terminal groups to PEG graft layers may cause additional interfacial forces to modulate the net interfacial interactions between PEG graft layers and proteins. In this study we investigated the effect of terminal sulfonate groups, characterizing PEG-aldehyde (PEG-CHO) and sulfonated PEG (PEG-SO3) graft layers by XPS and colloid probe AFM interaction force measurements as a function of ionic strength, in order to determine surface forces relevant to protein resistance and models of bio-interfacial interaction of such graft coatings. On the PEG-CHO surface the measured interaction force does not alter with ionic strength, typical of a repulsive steric barrier coating. An analogous repulsive interaction force of steric origin was also observed on the PEG-SO3 graft coating; however, the net interaction force changed with ionic strength. Interaction forces were modelled by steric and electrical double layer interaction theories, with fitting to a scaling theory model enabling determination of the spacing and stretching of the grafted chains. Albumin, fibrinogen, and lysozyme did not adsorb on the PEG-CHO coating, whereas the PEG graft with terminal sulfonate groups showed substantial adsorption of albumin but not fibrinogen or lysozyme from 0.15 M salt solutions. Under lower ionic strength conditions albumin adsorption was again minimized as a result of the increased electrical double-layer interaction observed with the PEG-SO3 modified surface. This unique and unexpected adsorption behaviour of albumin provides an alternative explanation to the "negative cilia" model used by others to rationalize observed thromboresistance on PEG-sulfonate coatings. Copyright © 2013 Elsevier B.V. All rights reserved.

Structure and property relations of macromolecular self-assemblies at interfaces

NASA Astrophysics Data System (ADS)

Yang, Zhihao

Hydrophilic polymer chains, poly(ethylene glycol) (PEG), are attached to glass surfaces by silylation of the silanol groups on glass surfaces with the omega-(methoxyl terminated PEG) trimethoxysilanes. These tethered polymer chains resemble the self-assembled monolayers (SAMs) of PEG, which exhibit excellent biocompatibility and provide a model system for studying the interactions of proteins with polymer surfaces. The low molecular weight PEGs tend to extend, forming a brush-like monolayer, whereas the longer polymer chains tend to interpenetrate each other, forming a mushroom-like PEG monolayer at the interface. Interactions between a plasma protein, bovine serum albumin, and the PEG-SAMs are investigated in terms of protein adsorption and diffusion on the surfaces by the technique of fluorescence recovery after photobleaching (FRAP). The diffusion and aggregation behaviors of the protein on the two monolayers are found to be quite different despite the similarities in adsorption and desorption behaviors. The results are analyzed with a hypothesis of the hydrated surface dynamics. A method of covalently bonding phospholipid molecules to silica substrates followed by loading with free phospholipids is demonstrated to form well organized and stable phospholipid self-assembled monolayers. Surfaces of such SAMs structurally mimic the aqueous sides of phospholipid bilayer membranes. The dynamics of phospholipids and an adsorbed protein, lipase, in the SAMs are probed with FRAP, in terms of lateral diffusion of both phospholipids and protein molecules. The esterase activity of lipase on the SAM surfaces is confirmed by the hydrolysis reaction of a substrate, umbelliferone stearate, showing such lipid SAMs posess biomembrane functionality in terms of interfacial activation of the membranous enzymes. Dynamics of polyethylene oxide and polypropylene oxide tri-block copolymers, PEO-PPO-PEO and PPO-PEO-PPO, at the air/water interface upon thermal stimulation is studied by surface light scattering, in terms of the dynamic surface tension changes in response to a temperature jump. The characteristic of the surface tension relaxation is found to be highly related to the molecular structure and concentration of the copolymers at the interface.

S. pombe CLASP needs dynein, not EB1 or CLIP170, to induce microtubule instability and slows polymerization rates at cell tips in a dynein-dependent manner

PubMed Central

Grallert, Agnes; Beuter, Christoph; Craven, Rachel A.; Bagley, Steve; Wilks, Deepti; Fleig, Ursula; Hagan, Iain M.

2006-01-01

The Schizosaccharomyces pombe CLIP170-associated protein (CLASP) Peg1 was identified in a screen for mutants with spindle formation defects and a screen for molecules that antagonized EB1 function. The conditional peg1.1 mutant enabled us to identify key features of Peg1 function. First, Peg1 was required to form a spindle and astral microtubules, yet destabilized interphase microtubules. Second, Peg1 was required to slow the polymerization rate of interphase microtubules that establish end-on contact with the cortex at cell tips. Third, Peg1 antagonized the action of S. pombe CLIP170 (Tip1) and EB1 (Mal3). Fourth, although Peg1 resembled higher eukaryotic CLASPs by physically associating with both Mal3 and Tip1, neither Tip1 nor Mal3 was required for Peg1 to destabilize interphase microtubules or for it to associate with microtubules. Conversely, neither Mal3 nor Tip1 required Peg1 to associate with microtubules or cell tips. Consistently, while mal3.Δ and tip1.Δ disrupted linear growth, corrupting peg1 + did not. Fifth, peg1.1 phenotypes resembled those arising from deletion of the single heavy or both light chains of fission yeast dynein. Furthermore, all interphase phenotypes arising from peg1 + manipulation relied on dynein function. Thus, the impact of S. pombe CLASP on interphase microtubule behavior is more closely aligned to dynein than EB1 or CLIP170. PMID:16951255

Polyurethane membranes for surgical gown applications

NASA Astrophysics Data System (ADS)

Ukpabi, Pauline Ozoemena

The Occupational Safety and Health Administration (OSHA) recently issued a directive requiring all employers to supply personnel protective equipment to employees who are at risk of exposure to blood or other potentially infectious body fluids. For the healthcare worker, a wide variety of surgical gowns is available commercially but there are concerns over their barrier effectiveness and/or wearer comfort. To successfully create a barrier fabric which combines resistance to fluid penetration with comfort, a complete understanding of the relationship between membrane structure and functional properties is required. In this study, we investigated the surface properties of hydrophilicity and hydrophobicity in polyurethane membranes intended for use in surgical gowns. The polyurethane membranes were grafted with side chains of varying lengths, polyethylene glycol (PEG) being used for the hydrophilic modifications and perfluoroalkyl compounds (a monofunctional acid and a difunctional amino alcohol) for the hydrophobic modifications. The hydrophilic treatment was intended to improve the comfort properties of monolithic membranes without adversely affecting their barrier properties. The hydrophobic treatment, on the other hand, was intended to improve the fluid repellency and hence barrier properties of microporous membranes without adversely affecting their comfort properties. Reflection infrared spectroscopy showed that fluorine was successfully grafted onto the polyurethane backbone during the hydrophobic modification, but was not sensitive enough to detect PEG grafting in leached polyethylene glycol-treated polyurethanes. X-ray photoelectron spectroscopy showed that the perfluoroalkylated polyurethanes contained up to 40% fluorine on their surfaces and the PEG-treated polyurethanes showed an increase in their C-O content over the unmodified polyurethane. Scanning electron microscopy not only showed that perfluoroalkylation yielded polyurethane membranes with very rough surfaces compared to the unmodified membrane, it also showed varying degrees of surface roughness on the perfluoroalkylated polyurethanes depending on whether the monofunctional acid or the difunctional amino alcohol was used as modifier. The PEG-treated samples exhibited smooth surfaces under the SEM. Perfluoroalkylation yielded samples with slightly higher contact angles than the untreated polyurethane while the PEG treatment resulted in polyurethanes with lower contact angles than the untreated polyurethane. The perfluoroalkylated materials were more thermally stable than the unmodified polyurethanes.

Double hydrophilic block copolymer controlled growth and self-assembly of CaCO3 multilayered structures at the air/water interface.

PubMed

Gao, Yun-Xiang; Yu, Shu-Hong; Guo, Xiao-Hui

2006-07-04

Double hydrophilic block copolymers PEG-b-PEI-linear with different PEI block lengths have been examined for CaCO3 mineralization at the air/water interface. The results demonstrated that either PEI length or the solution acidity had a significant influence on the morphogenesis of vaterite crystals at the air/water interface. A possible mechanism for the stratification of CaCO3 vaterite crystals has been proposed. Increasing either PEI length or the initial pH value of the solution will decrease the density of the PEG block anchored on the binding interface and result in exposing more space as binding interface to solution and favoring the subnucleation and stratification growth on the polymer-CaCO3 interface. In contrast, higher density of PEG blocks will stabilize the growing crystals more efficiently and inhibit subnucleation on the polymer-CaCO3 interface, and thus prevent the formation of stratified structures. This study provides an example that it is possible to access morphogenesis of calcium carbonate structures by a combination of a block copolymer with the air/water interface.

Comparative study on digestive lipase activities on the self emulsifying excipient Labrasol, medium chain glycerides and PEG esters.

PubMed

Fernandez, Sylvie; Jannin, Vincent; Rodier, Jean-David; Ritter, Nicolas; Mahler, Bruno; Carrière, Frédéric

2007-05-01

Labrasol is a lipid-based self-emulsifying excipient used in the preparation of lipophilic drugs intended for oral delivery. It is mainly composed of PEG esters and glycerides with medium acyl chains, which are potential substrates for digestive lipases. The hydrolysis of Labrasol by porcine pancreatic extracts, human pancreatic juice and several purified digestive lipases was investigated in the present study. Classical human pancreatic lipase (HPL) and porcine pancreatic lipase, which are the main lipases involved in the digestion of dietary triglycerides, showed very low levels of activity on the entire Labrasol excipient as well as on separated fractions of glycerides and PEG esters. On the other hand, gastric lipase, pancreatic lipase-related protein 2 (PLRP2) and carboxyl ester hydrolase (CEH) showed high specific activities on Labrasol. These lipases were found to hydrolyze the main components of Labrasol (PEG esters and monoglycerides) used as individual substrates, whereas these esters were found to be poor substrates for HPL. The lipolytic activity of pancreatic extracts and human pancreatic juice on Labrasol(R) is therefore mainly due to the combined action of CEH and PLRP2. These two pancreatic enzymes, together with gastric lipase, are probably the main enzymes involved in the in vivo lipolysis of Labrasol taken orally.

Thickness Dependent Effective Viscosity of a Polymer Solution near an Interface Probed by a Quartz Crystal Microbalance with Dissipation Method

PubMed Central

Fang, Jiajie; Zhu, Tao; Sheng, Jie; Jiang, Zhongying; Ma, Yuqiang

2015-01-01

The solution viscosity near an interface, which affects the solution behavior and the molecular dynamics in the solution, differs from the bulk. This paper measured the effective viscosity of a dilute poly (ethylene glycol) (PEG) solution adjacent to a Au electrode using the quartz crystal microbalance with dissipation (QCM-D) technique. We evidenced that the effect of an adsorbed PEG layer can be ignored, and calculated the zero shear rate effective viscosity to remove attenuation of high shear frequency oscillations. By increasing the overtone n from 3 to 13, the thickness of the sensed polymer solution decreased from ~70 to 30 nm. The zero shear rate effective viscosity of the polymer solution and longest relaxation time of PEG chains within it decrease with increasing solution thickness. The change trends are independent of the relation between the apparent viscosity and shear frequency and the values of the involved parameter, suggesting that the polymer solution and polymer chains closer to a solid substrate have a greater effective viscosity and slower relaxation mode, respectively. This method can study the effect of an interface presence on behavior and phenomena relating to the effective viscosity of polymer solutions, including the dynamics of discrete polymer chains. PMID:25684747

Superparamagnetic iron-oxide nanoparticles mPEG350- and mPEG2000-coated: cell uptake and biocompatibility evaluation.

PubMed

Silva, Adny H; Lima, Enio; Mansilla, Marcelo Vasquez; Zysler, Roberto D; Troiani, Horacio; Pisciotti, Mary Luz Mojica; Locatelli, Claudriana; Benech, Juan C; Oddone, Natalia; Zoldan, Vinícius C; Winter, Evelyn; Pasa, André A; Creczynski-Pasa, Tânia B

2016-05-01

Superparamagnetic iron oxide nanoparticles (SPIONS) were synthesized by thermal decomposition of an organometallic precursor at high temperature and coated with a bi-layer composed of oleic acid and methoxy-polyethylene glycol-phospholipid. The formulations were named SPION-PEG350 and SPION-PEG2000. Transmission electron microscopy, X-ray diffraction and magnetic measurements show that the SPIONs are near-spherical, well-crystalline, and have high saturation magnetization and susceptibility. FTIR spectroscopy identifies the presence of oleic acid and of the conjugates mPEG for each sample. In vitro biocompatibility of SPIONS was investigated using three cell lines; up to 100μg/ml SPION-PEG350 showed non-toxicity, while SPION-PEG2000 showed no signal of toxicity even up to 200μg/ml. The uptake of SPIONS was detected using magnetization measurement, confocal and atomic force microscopy. SPION-PEG2000 presented the highest internalization capacity, which should be correlated with the mPEG chain size. The in vivo results suggested that SPION-PEG2000 administration in mice triggered liver and kidney injury. The potential use of superparamagnetic iron oxide nanoparticles (SPIONS) in the clinical setting have been studied by many researchers. The authors synthesized two types of SPIONS here and investigated the physical properties and biological compatibility. The findings should provide more data on the design of SPIONS for clinical application in the future. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of molecular weight of polyethylene glycol on the rheological properties of fumed silica-polyethylene glycol shear thickening fluid

NASA Astrophysics Data System (ADS)

Singh, Mansi; Verma, Sanjeev K.; Biswas, Ipsita; Mehta, Rajeev

2018-05-01

The steady-shear viscosity and dynamic visco-elastic behavior of suspensions of 20 wt% fumed silica-polyethylene glycol (PEG200) shear thickening fluid (STF) with different concentrations of various molecular weight PEG (4600, 6000 and 10000) has been studied. The results demonstrate that with an increase in the molecular weight of dispersing medium, the shear thickening parameters are significantly enhanced. In steady-state rheology, addition of PEG6000 as an additive results in high shear thickening at both low and high temperatures whereas in dynamic state, PEG4600 gives high values of all dynamic parameters. Additionally, long polymer can interconnect several particles, acting as cross-links which explain the mechanism of the enhancement in viscosity. Interestingly, compositions having PEG10000 as additive exhibits shear thinning rheology. Long polymer chains increases hydrodynamic forces thus aggregation of particles increases. Also, the results demonstrate the effect of high molecular weight PEGs on the elasticity and stability of the STF, which is important with regard to high impact resisting applications.

PNA-PEG modified silicon platforms as functional bio-interfaces for applications in DNA microarrays and biosensors.

PubMed

Cattani-Scholz, Anna; Pedone, Daniel; Blobner, Florian; Abstreiter, Gerhard; Schwartz, Jeffrey; Tornow, Marc; Andruzzi, Luisa

2009-03-09

The synthesis and characterization of two types of silicon-based biofunctional interfaces are reported; each interface bonds a dense layer of poly(ethylene glycol) (PEG(n)) and peptide nucleic acid (PNA) probes. Phosphonate self-assembled monolayers were derivatized with PNA using a maleimido-terminated PEG(45). Similarly, siloxane monolayers were functionalized with PNA using a maleimido-terminated PEG(45) spacer and were subsequently modified with a shorter methoxy-terminated PEG(12) ("back-filling"). The long PEG(45) spacer was used to distance the PNA probe from the surface and to minimize undesirable nonspecific adsorption of DNA analyte. The short PEG(12) "back-filler" was used to provide additional passivation of the surface against nonspecific DNA adsorption. X-ray photoelectron spectroscopic (XPS) analysis near the C 1s and N 1s ionization edges was done to characterize chemical groups formed in the near-surface region, which confirmed binding of PEG and PNA to the phosphonate and silane films. XPS also indicated that additional PEG chains were tethered to the surface during the back-filling process. Fluorescence hybridization experiments were carried out with complementary and noncDNA strands; both phosphonate and siloxane biofunctional surfaces were effective for hybridization of cDNA strands and significantly reduced nonspecific adsorption of the analyte. Spatial patterns were prepared by polydimethylsiloxane (PDMS) micromolding on the PNA-functionalized surfaces; selective hybridization of fluorescently labeled DNA was shown at the PNA functionalized regions, and physisorption at the probe-less PEG-functionalized regions was dramatically reduced. These results show that PNA-PEG derivatized phosphonate monolayers hold promise for the smooth integration of device surface chemistry with semiconductor technology for the fabrication of DNA biosensors. In addition, our results confirm that PNA-PEG derivatized self-assembled carboxyalkylsiloxane films are promising substrates for DNA microarray applications.

Development of a novel biocompatible poly(ethylene glycol)-block-poly(γ-cholesterol-L-glutamate) as hydrophobic drug carrier.

PubMed

Ma, Qing; Li, Bo; Yu, Yiyi; Zhang, Ying; Wu, Yang; Ren, Wen; Zheng, Yu; He, Jun; Xie, Yongmei; Song, Xiangrong; He, Gu

2013-03-10

A novel biomaterial poly(ethylene glycol)-block-poly(γ-cholesterol-l-glutamate) (mPEG-PCHLG) was designed and synthesized by introducing cholesterol side chains into this pegylated poly(amino acid) copolymers to enlarge the core space to increase the drug capacity. Paclitaxel (PTX) loaded mPEG-PCHLG nanoparticles (PTX-mPEG-PCHLG-Nps) were developed for the first time. The preparation method of nanoparticles was screened and optimized systemically. The optimal PTX-mPEG-PCHLG-Nps with the average diameter of 213.71 nm were constructed through the O/W single-emulsion solvent evaporation method. The entrapment efficiency and drug loading was 38.02 ± 4.51% and 93.90 ± 4.56%, respectively. PTX-mPEG-PCHLG-Nps were spherical and well-dispersed and displayed a dramatic sustained-release property. The in vitro cytotoxicity experiments demonstrated that the blank mPEG-PCHLG nanoparticles had no cytotoxicities on four tumor cell lines including A549, HepG-2, MCF-7 and C26, which implied that mPEG-PCHLG might be biocompatible. PTX-mPEG-PCHLG-Nps obtained the same cell growth inhibition activities as free PTX when incubated with the above tumor cells for 48h. It can be inferred that PTX-mPEG-PCHLG-Nps could probably have higher anticancer efficacy due to the inadequate release of PTX from nanoparticles. PTX-mPEG-PCHLG-Nps achieved the highest antitumor activity in A549 rather than HepG-2, MCF-7 and C26, thus PTX-mPEG-PCHLG-Nps could have a potential application in lung cancer therapy. All the data indicated that mPEG-PCHLG was one of biocompatible biomaterials and worth being widely investigated as hydrophobic antitumor drug carrier. Copyright © 2013 Elsevier B.V. All rights reserved.

Characterization of singly and multiply PEGylated insulin isomers by reversed-phase ultra-performance liquid chromatography interfaced with ion mobility mass spectrometry.

PubMed

Gerislioglu, Selim; Adams, Scott R; Wesdemiotis, Chrys

2018-04-03

Conjugation of poly(ethylene glycol) (PEG) to protein drugs (PEGylation) is increasingly utilized in the biotherapeutics field because it improves significantly the drugs' circulatory half-life, solubility, and shelf-life. The activity of a PEGylated drug depends on the number, size, and location of the attached PEG chain(s). This study introduces a 2D separation approach, including reversed-phase ultra-performance liquid chromatography (RP-UPLC) and ion mobility mass spectrometry (IM-MS), in order to determine the structural properties of the conjugates, as demonstrated for a PEGylated insulin sample that was prepared by random amine PEGylation. The UPLC dimension allowed separation based on polarity. Electrospray ionization (ESI) of the eluates followed by in-source dissociation (ISD) truncated the PEG chains and created insulin fragments that provided site-specific information based on whether they contained a marker at the potential conjugation sites. Separation of the latter fragments by size and charge in the orthogonal IM dimension (pseudo-4D UPLC-ISD-IM-MS approach) enabled clear detection and identification of the positional isomers formed upon PEGylation. The results showed a highly heterogeneous mixture of singly and multiply conjugated isomers plus unconjugated material. PEGylation was observed on all three possible attachment sites (ε-NH 2 of LysB29, A- and B-chain N-termini). Each PEGylation site was validated by analysis of the same product after disulfide bond cleavage, so that the PEGylated A- and B- chain could be individually characterized with the same pseudo-4D UPLC-ISD-IM-MS method. Copyright © 2018 Elsevier B.V. All rights reserved.

Synthetically Simple, Highly Resilient Hydrogels

PubMed Central

Cui, Jun; Lackey, Melissa A.; Madkour, Ahmad E.; Saffer, Erika M.; Griffin, David M.; Bhatia, Surita R.; Crosby, Alfred J.; Tew, Gregory N.

2014-01-01

Highly resilient synthetic hydrogels were synthesized by using the efficient thiol-norbornene chemistry to cross-link hydrophilic poly(ethylene glycol) (PEG) and hydrophobic polydimethylsiloxane (PDMS) polymer chains. The swelling and mechanical properties of the hydrogels were well-controlled by the relative amounts of PEG and PDMS. In addition, the mechanical energy storage efficiency (resilience) was more than 97% at strains up to 300%. This is comparable with one of the most resilient materials known: natural resilin, an elastic protein found in many insects, such as in the tendons of fleas and the wings of dragonflies. The high resilience of these hydrogels can be attributed to the well-defined network structure provided by the versatile chemistry, low cross-link density, and lack of secondary structure in the polymer chains. PMID:22372639

Forces and Dynamics of Glucose and Inhibitor Binding to Sodium Glucose Co-transporter SGLT1 Studied by Single Molecule Force Spectroscopy*

PubMed Central

Neundlinger, Isabel; Puntheeranurak, Theeraporn; Wildling, Linda; Rankl, Christian; Wang, Lai-Xi; Gruber, Hermann J.; Kinne, Rolf K. H.; Hinterdorfer, Peter

2014-01-01

Single molecule force spectroscopy was employed to investigate the dynamics of the sodium glucose co-transporter (SGLT1) upon substrate and inhibitor binding on the single molecule level. CHO cells stably expressing rbSGLT1 were probed by using atomic force microscopy tips carrying either thioglucose, 2′-aminoethyl β-d-glucopyranoside, or aminophlorizin. Poly(ethylene glycol) (PEG) chains of different length and varying end groups were used as tether. Experiments were performed at 10, 25 and 37 °C to address different conformational states of SGLT1. Unbinding forces between ligands and SGLT1 were recorded at different loading rates by changing the retraction velocity, yielding binding probability, width of energy barrier of the binding pocket, and the kinetic off rate constant of the binding reaction. With increasing temperature, width of energy barrier and average life time increased for the interaction of SGLT1 with thioglucose (coupled via acrylamide to a long PEG) but decreased for aminophlorizin binding. The former indicates that in the membrane-bound SGLT1 the pathway to sugar translocation involves several steps with different temperature sensitivity. The latter suggests that also the aglucon binding sites for transport inhibitors have specific, temperature-sensitive conformations. PMID:24962566

A coarse grained molecular dynamics simulation study on the structural properties of carbon nanotube-dendrimer composites.

PubMed

Kavyani, Sajjad; Dadvar, Mitra; Modarress, Hamid; Amjad-Iranagh, Sepideh

2018-04-25

By employing coarse grained (CG) molecular dynamics (MD) simulation, the effect of the size and hydrophilic/hydrophobic properties of the interior/exterior structures of the dendrimers in carbon nanotube (CNT)-dendrimer composites has been studied, to find a stable composite with high solubility in water and the capability to be used in drug delivery applications. For this purpose, composites consisting of core-shell dendrimer complexes including: [PPI{core}-PAMAM{shell}], [PAMAM{core}-polyethyleneglycol (PEG){shell}] and [PAMAM{core}-fattyacid (FTA){shell}] were constructed. A new CG model for the fatty acid (FTA) molecules as functionalized to the dendrimer was developed, which, unlike the previous models, could generate the structural conformations of the FTA properly. The obtained results indicated that the dendrimer complexes with short FTA chains can form stable composites with the CNT. Also, it was found that the pristine PAMAM and PPI-PAMAM with small PPI, and PAMAM-PEG dendrimers with short PEG chains, can distribute their chains into the water medium and interact with the CNT efficiently, to form a stable water-soluble CNT-dendrimer composite. The results demonstrated that the structural difference between the interior and exterior of a core-shell dendrimer complex can prevent the core and the interior layers of the dendrimer complex from interacting with the CNT. An overall analysis of the results manifested that the CNT-PAMAM:4-PEG:4 is the most stable composite, due to strong binding of the dendrimer with the CNT while also having high solubility in water, and its core retains its structure properly and unchanged, suitable for encapsulating drugs in the targeted delivery applications.

Synthesis and characterization of amphiphilic block polymer poly(ethylene glycol)-poly(propylene carbonate)-poly(ethylene glycol) for drug delivery.

PubMed

Li, Hongchun; Niu, Yongsheng

2018-08-01

A novel amphiphilic block polymer poly(ethylene glycol)-poly(propylene carbonate)-poly(ethylene glycol) (PEG-PPC-PEG) was synthesized via the dicyclohexylcarbodiimide condensation reaction of double PEG-bis-amine and HOOC-PPC-COOH. The obtained copolymer was characterized by NMR to determine its structure. Using the PEG-PPC-PEG as the carrier and using doxorubicin (DOX) as a model drug, DOX-loaded nanoparticles with core shell structure were synthesized by self-assembly in water. The nanoparticles properties such as particle size, drug loading, encapsulation efficiency (EE) and drug release behavior were investigated as a function of the hydrophobic block length of PPC segments and compared with each other. The results showed that the EE was up to 88.8%. Nanoparticles were found to have a certain effect on the controlled release of DOX. Copyright © 2018 Elsevier B.V. All rights reserved.

Molecular identification of Mango, Mangifera indica L.var. totupura

PubMed Central

Jagarlamudi, Sankar; G, Rosaiah; Kurapati, Ravi Kumar; Pinnamaneni, Rajasekhar

2011-01-01

Mango (>Mangifera indica) belonging to Anacardiaceae family is a fruit that grows in tropical regions. It is considered as the King of fruits. The present work was taken up to identify a tool in identifying the mango species at the molecular level. The chloroplast trnL-F region was amplified from extracted total genomic DNA using the polymerase chain reaction (PCR) and sequenced. Sequence of the dominant DGGE band revealed that Mangifera indica in tested leaves was Mangifera indica (100% similarity to the ITS sequences of Mangifera indica). This sequence was deposited in NCBI with the accession no. GQ927757. Abbreviations AFLP - Amplified fragment length polymorphism , cpDNA - Chloroplast DNA, DDGE - Denaturing gradient gel electrophoresis, DNA - Deoxyribo nucleic acid, EDTA - Ethylenediamine tetraacetic acid, HCl - Hydrochloric acid, ISSR - Inter simple sequence repeats, ITS - Internal transcribed spacer, MATAB - Methyl Ammonium Bromide, Na2SO3 - Sodium sulphite, NaCl - Sodium chloride, NCBI - National Centre for Biotechnology Information, PCR - Polymerase chain reaction, PEG - Polyethylene glycol, RAPD - Randomly amplified polymorphic DNA, trnL-F - Transfer RNA genes start codon- termination codon. PMID:21423885

Thermostability of native and pegylated Myceliophthora thermophila laccase in aqueous and mixed solvents.

PubMed

López-Cruz, J I; Viniegra-Gonzalez, G; Hernández-Arana, A

2006-01-01

A commercial preparation of laccase (EC 1.10.3.2), cloned from Myceliophthora thermophila and expressed in Aspergillus oryzae (MtL), was purified and modified by conjugation with poly(ethylene glycol) (M(r) = 5000) and is labeled PEG-MtL. Native enzyme was found to have a molecular mass of 80 kDa, as determined by gel filtration, and 110 kDa, by SDS-PAGE. The oxidative dimerization of 2,6-dimethoxyphenol (DMP) to produce the corresponding dibenzoquinone was catalyzed by MtL in a manner comparable to that for a diffusion-controlled reaction (k(cat)/K(M) approximately = 10(8) M(-)(1) s(-)(1) and E(a) approximately = 18 kJ M(-)(1)). PEG-MtL was found, by TNBS titration, to have blocked 54% of lysine groups; its hydrodynamic and charge properties were different from those of MtL. Catalytic efficiency (k(cat)/K(M)) of PEG-MtL was similar to that of MtL with DMP as substrate; however, k(cat)/K(M) was 2-fold reduced for the reaction in which 2',2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) is oxidized to form a radical cation. E(a) values were similar in both enzyme preparations when assayed in buffered solutions. Far-UV CD spectra were similar for MtL and PEG-MtL and consistent with a protein rich in beta-sheet structure with negligible content of alpha-helices. A blue shift of near-UV CD spectrum for PEG-MtL as compared to MtL was consistent with the decreased polarity of the tyrosyl side chains upon PEG conjugation. Also the blue band of the copper active site was shifted from lambda approximately 610 nm (MtL) to lambda approximately 575 nm (PEG-MtL). Scanning microcalorimetry showed small denaturation enthalpies (6.3 and 7.5 J g(-)(1) for MtL and PEG-MtL, respectively), indicating the high stability of the beta-sheet folding pattern of laccases. However, PEG-MtL proved to be more stable, its half-denaturation temperature being 2 degrees C higher than that of MtL. In 30% alcohol, pegylated laccase showed slower enzyme-activity decay rates than the unmodified enzyme; this behavior was caused by a decrease in the activation entropy of the denaturation reaction. Results can be explained by entropic stabilization by PEG conjugation because of the restricted motion of some surface amino acid side chains, which results in a more stable active site.

Enthalpic and Entropic Competition in Blends of Self-Suspended Hairy Nanoparticles

NASA Astrophysics Data System (ADS)

Choudhury, Snehashis; Agrawal, Akanksha; Archer, Lynden

Self-suspended hairy nanoparticles, where polymer chains are grafted onto nanoparticles, have attracted significant recent attention. These materials have been reported to manifest several interesting phenomena like thermal jamming, slowing-down of polymer chain dynamics, as well as small-strain stress overshoots during start-up of steady shear. The entropic penalty on tethered polymers produced by the requirement that they fill the space between the nanoparticle cores explain most of these behaviors. Here, we show that the entropic attraction between tethered polymer chains can be manipulated in mixtures of hairy nanoparticles using different polymer chemistry to design materials with unusual characteristics. Specifically, the degree of interpenetration of polymer chains can be controlled by tuning their interaction parameter (χ) . For SiO2-PEG/SiO2-PMMA blends, oscillatory rheological measurements show that the plateau modulus and yielding energy are significantly increased, while an opposite effect is seen with SiO2-PEG/SiO2-PI blends. More subtle effects of this enthalpy-entropy competition are well captured in Dielectric Spectroscopy measurements and SAXS experiments that can be used to quantify the degree of stretch and interdigitation of polymer chains.

Thermal and rheological properties of L-polylactide/polyethylene glycol/silicate nanocomposites films.

PubMed

Ahmed, Jasim; Varshney, Sunil K; Auras, Rafael; Hwang, Sung W

2010-10-01

The melt rheology and thermal properties of polylactide (PLA)-based nanocomposite films that were prepared by solvent casting method with L-PLA, polyethylene glycol (PEG), and montmorillonite clay were studied. The neat PLA showed predominantly solid-like behavior (G' > G″) and the complex viscosity (η*) decreased systematically as the temperature increased from 184 to 196 °C. The elastic modulus (G') of PLA/clay blend showed a significant improvement in the magnitude in the melt, while clay concentration was at 6% wt or higher. At similar condition, PEG dramatically reduced dynamic modulii and complex viscosity of PLA/PEG blend as function of concentration. A nanocomposite blend of PLA/PEG/clay (74/20/6) when compared to the neat polymer and PLA/PEG blend exhibited intermediate values of elastic modulus (G') and complex viscosity (η*) with excellent flexibility. Thermal analysis of different clay loading blends indicated that the melting temperature (T(m)) and glass transition temperature (T(g)) remained unaffected irrespective of clay concentration due to immobilization of polymer chain in the clay nanocomposite. PEG incorporation reduced the T(g) and the T(m) of the blends (PLA/PEG and PLA/PEG/clay) significantly, however, crystallinity increased in the similar condition. The transmission electron microscopy (TEM) image of nanocomposite films indicated good compatibility between PLA and PEG, whereas clay was not thoroughly distributed in the PLA matrix and remained as clusters. The percent crystallinity obtained by X-ray was significantly higher than that of differential scanning calorimeter (DSC) data for PLA.

PEGylated human serum albumin (HSA) nanoparticles: preparation, characterization and quantification of the PEGylation extent

NASA Astrophysics Data System (ADS)

Fahrländer, E.; Schelhaas, S.; Jacobs, A. H.; Langer, K.

2015-04-01

Modification with poly(ethylene glycol) (PEG) is a widely used method for the prolongation of plasma half-life of colloidal carrier systems such as nanoparticles prepared from human serum albumin (HSA). However, the quantification of the PEGylation extent is still challenging. Moreover, the influence of different PEG derivatives, which are commonly used for nanoparticle conjugation, has not been investigated so far. The objective of the present study is to develop a method for the quantification of PEG and to monitor the influence of diverse PEG reagents on the amount of PEG linked to the surface of HSA nanoparticles. A size exclusion chromatography method with refractive index detection was established which enabled the quantification of unreacted PEG in the supernatant. The achieved results were confirmed using a fluorescent PEG derivative, which was detected by photometry and fluorimetry. Additionally, PEGylated HSA nanoparticles were enzymatically digested and the linked amount of fluorescently active PEG was directly determined. All the analytical methods confirmed that under optimized PEGylation conditions a PEGylation efficiency of up to 0.5 mg PEG per mg nanoparticle could be achieved. Model calculations made a ‘brush’ conformation of the PEG chains on the particle surface very likely. By incubating the nanoparticles with fetal bovine serum the reduced adsorption of serum proteins on PEGylated HSA nanoparticles compared to non-PEGylated HSA nanoparticles was demonstrated using sodium dodecylsulfate polyacrylamide gel electrophoresis. Finally, the positive effect of PEGylation on plasma half-life was demonstrated in an in vivo study in mice. Compared to unmodified nanoparticles the PEGylation led to a four times larger plasma half-life.

Extension arm facilitated pegylation of alphaalpha-hemoglobin with modifications targeted exclusively to amino groups: functional and structural advantages of free Cys-93(beta) in the PEG-Hb adduct.

PubMed

Li, Dongxia; Hu, Tao; Manjula, Belur N; Acharya, Seetharama A

2009-11-01

Cys-93(beta) of hemoglobin (Hb) was reversibly protected as a mixed disulfide with thiopyridine during extension arm facilitated (EAF) PEGylation and its influence on the structural and functional properties of the EAF-PEG-Hb has been investigated. Avoiding PEGylation of Cys-93(beta) in the EAF-PEG-Hb lowers the level of perturbation of heme pocket, alpha1beta2 interface, autoxidation, heme loss, and the O(2) affinity, as compared to the EAF-PEG-Hb with PEGylation of Cys-93(beta).The structural and functional advantages of reversible protection of Cys-93(beta) during EAF PEGylation of oxy-Hb has been compared with Euro PEG-Hb generated by EAF PEGylation of deoxy Hb where Cys-93(beta) is free in the final product. The alphaalpha-fumaryl cross-linking and EAF PEGylation targeted exclusively to Lys residues has been combined together for generation of second-generation EAF-PEG-Hb with lower oxygen affinity. The PEG chains engineered on Lys as well as PEGylation of Cys-93(beta) independently contribute to the stabilization of oxy conformation of Hb and hence increase the oxygen affinity of Hb. However, oxygen affinity of the EAF-PEG-alphaalpha-Hb is more sensitive to the presence of PEGylation on Cys-93(beta) than that of the EAF-PEG-Hb. The present modified EAF PEGylation platform is expected to facilitate the design of novel versions of the EAF-PEG-Hbs that can now integrate the advantages of avoiding PEGylation of Cys-93(beta).

Carbon capture from natural gas using multi-walled CNTs based mixed matrix membranes.

PubMed

Hussain, Abid; Farrukh, Sarah; Hussain, Arshad; Ayoub, Muhammad

2017-12-05

Most of the polymers and their blends, utilized in carbon capture membranes, are costly, but cellulose acetate (CA) being inexpensive is a lucrative choice. In this research, pure and mixed matrix membranes (MMMs) have been fabricated to capture carbon from natural gas. Polyethylene glycol (PEG) has been utilized in the fabrication of membranes to modify the chain flexibility of polymers. Multi-walled carbon nanotubes (MWCNTs) provide mechanical strength, thermal stability, an extra free path for CO 2 molecules and augment CO 2 /CH 4 selectivity. Membranes of pure CA, CA/PEG blend of different PEG concentrations (5%, 10%, 15%) and CA/PEG/MWCNTs blend of 10% PEG with different MWCNTs concentrations (5%, 10%, 15%) were prepared in acetone using solution casting techniques. Fabricated membranes were characterized using SEM, TGA and tensile testing. Permeation results revealed remarkable improvement in CO 2 /CH 4 selectivity. In single gas experiments, CO 2 /CH 4 selectivity is enhanced 8 times for pure membranes containing 10% PEG and 14 times for MMMs containing 10% MWCNTs. In mix gas experiments, the CO 2 /CH 4 selectivity is increased 13 times for 10% PEG and 18 times for MMMs with 10% MWCNTs. Fabricated MMMs have a tensile strength of 13 MPa and are more thermally stable than CA membranes.

MUC-1 aptamer-conjugated dye-doped silica nanoparticles for MCF-7 cells detection.

PubMed

Cai, Li; Chen, Ze-Zhong; Chen, Min-Yan; Tang, Hong-Wu; Pang, Dai-Wen

2013-01-01

In this work, we have prepared three types of aptamer-conjugated Rubpy-doped silica nanoparticles for Human breast carcinoma MCF-7 cells labeling. Probe A is prepared through covalent conjugation between amine-labeled MUC-1 aptamer and carboxyl-modified Rubpy-doped NPs (NPs-aptamer). Probe B is prepared based on the interaction between biotin-labeled MUC-1 aptamer and avidin-conjugated Rubpy-doped NPs (NPs-avidin-biotin-aptamer). For Probe C, there is a PEG with flexible long chain as the bridge between avidin and the NPs (NPs-PEG-avidin-biotin-aptamer). In addition, we further investigate the practical number of MUC-1 aptamers on an NP of each probe using hoechst33258 dye. The binding efficiency of MUC-1 aptamer on the three types of probes as follows: Probe A < Probe B < Probe C. In addition, microscopic fluorescence imaging shows that Probe C containing the PEG molecules can be effectively applied for the recognition of MUC-1 protein in human breast carcinoma MCF-7 cells thus demonstrates that the PEG with flexible long chain as the bridge between the aptamer and NP can greatly enhances the freedom of MUC-1 aptamer. Compared with common organic dyes, the dye-doped silica nanoparticles serve as a stable bioprobe because of their facile conjugation with the desirable biomolecules, and have exhibited great potential in bioanalysis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Microstructure of Pharmaceutical Semicrystalline Dispersions: The Significance of Polymer Conformation.

PubMed

Van Duong, Tu; Goderis, Bart; Van Humbeeck, Jan; Van den Mooter, Guy

2018-02-05

The microstructure of pharmaceutical semicrystalline solid dispersions has attracted extensive attention due to its complexity that might result in the diversity in physical stability, dissolution behavior, and pharmaceutical performance of the systems. Numerous factors have been reported that dictate the microstructure of semicrystalline dispersions. Nevertheless, the importance of the complicated conformation of the polymer has never been elucidated. In this study, we investigate the microstructure of dispersions of polyethylene glycol and active pharmaceutical ingredients by small-angle X-ray scattering and high performance differential scanning calorimetry. Polyethylene glycol with molecular weight of 2000 g/mol (PEG2000) and 6000 g/mol (PEG6000) exhibited remarkable discrepancy in the lamellar periodicity in dispersions with APIs which was attributed to the differences in their folding behavior. The long period of PEG2000 always decreased upon aging-induced exclusion of APIs from the interlamellar region of extended chain crystals whereas the periodicity of PEG6000 may decrease or increase during storage as a consequence of the competition between the drug segregation and the lamellar thickening from nonintegral-folded into integral-folded chain crystals. These processes were in turn significantly influenced by the crystallization tendency of the pharmaceutical compounds, drug-polymer interactions, as well as the dispersion composition and crystallization temperature. This study highlights the significance of the polymer conformation on the microstructure of semicrystalline systems that is critical for the preparation of solid dispersions with consistent and reproducible quality.

Hemocompatibility and oxygenation performance of polysulfone membranes grafted with polyethylene glycol and heparin by plasma-induced surface modification.

PubMed

Wang, Weiping; Zheng, Zhi; Huang, Xin; Fan, Wenling; Yu, Wenkui; Zhang, Zhibing; Li, Lei; Mao, Chun

2017-10-01

Polyethylene glycol (PEG) and heparin (Hep) were grafted onto polysulfone (PSF) membrane by plasma-induced surface modification to prepare PSF-PEG-Hep membranes used for artificial lung. The effects of plasma treatment parameters, including power, gas type, gas flow rate, and treatment time, were investigated, and different PEG chains were bonded covalently onto the surface in the postplasma grafting process. Membrane surfaces were characterized by water contact angle, PEG grafting degree, attenuated total reflectance-Fourier transform infrared spectroscopy, ultraviolet-visible spectrophotometry, X-ray photoelectron spectroscopy, critical water permeability pressure, and scanning electron microscopy. Protein adsorption, platelet adhesion, and coagulation tests showed significant improvement in the hemocompatibility of PSF-PEG-Hep membranes compared to pristine PSF membrane. Gas exchange tests through PSF-PEG6000-Hep membrane showed that when the flow rate of porcine blood reached 5.0 L/min, the permeation fluxes of O 2 and CO 2 reached 192.6 and 166.9 mL/min, respectively, which were close to the gas exchange capacity of a commercial membrane oxygenator. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1737-1746, 2017. © 2016 Wiley Periodicals, Inc.

Thiolation mediated pegylation platform to generate functional universal red blood cells.

PubMed

Nacharaju, Parimala; Manjula, Belur N; Acharya, Seetharama A

2007-01-01

The PEGylation that adds an extension arm on protein amino groups with the conservation of their positive charge masks the A and D antigens of erythrocytes efficiently. In the present study, the efficiency of masking the antigens of RBC by PEGylation protocols that do not conserve the charge with and without adding extension arms is compared. The conjugation of PEG-5000 to RBCs through the addition of extension arms masked the D antigen more efficiently than the other protocol. A combination of PEG-5 K and PEG-20 K is needed to mask the A antigen, irrespective of the PEGylation approach. The oxygen affinity of the PEGylated RBCs increased by the extension arm facilitated PEGylation. The protocol involving the conjugation of PEG-chains without adding extension arm did not alter the oxygen affinity of RBCs. A combination of PEGylation protocols is an alternate strategy to generate universal red blood cells with good levels of oxygen affinity.

Hyaluronan polymer length, grafting density, and surface poly(ethylene glycol) coating influence in vivo circulation and tumor targeting of hyaluronan-grafted liposomes.

PubMed

Qhattal, Hussaini Syed Sha; Hye, Tanvirul; Alali, Amer; Liu, Xinli

2014-06-24

Hyaluronan-grafted liposomes (HA-liposomes) preferentially target CD44-overexpressing tumor cells in vitro via receptor-mediated endocytosis. We investigated the pharmacokinetics and biodistribution of HA-liposomes with various sizes of HA (MW 5-8, 50-60, and 175-350 kDa) in mice. Incorporation of negatively charged HA on the liposome surface compromised its blood circulation time, which led to decreased tumor accumulation in CD44+ human breast cancer MDA-MB-231 xenografts compared to PEGylated liposomes (PEG-5000). Clearance of HA-liposomes was HA polymer length-dependent; high MW (175-350 kDa, highest ligand binding affinity) HA-liposomes displayed faster clearance compared to low MW (5-8, 50-60 kDa) HA-liposomes or PEGylated liposomes. Surface HA ligand density can also affect clearance of HA-liposomes. Thus, HA is not an effective stealth coating material. When dual coating of PEG and HA was used, the PEG-HA-liposomes displayed similar blood circulation time and tumor accumulation to that of the PEGylated liposomes; however, the PEG-HA-liposomes displayed better cellular internalization capability in vivo. Tumor histology showed that PEG-HA-liposomes had a more direct association with CD44+ cancer cells, while PEGylated liposomes located predominantly in the tumor periphery, with less association with CD44+ cells. Flow cytometry analysis of ex vivo tumor cells showed that PEG-HA-liposomes had significantly higher tumor cell internalization compared to PEGylated liposomes. This study demonstrates that a long blood circulation time is critical for active tumor targeting. Furthermore, the use of the tumor-targeting ligand HA does not increase total tumor accumulation of actively targeted liposomes in solid tumors; however, it can enhance intracellular delivery.

Optimization of Serine Protease Purification from Mango (Mangifera indica cv. Chokanan) Peel in Polyethylene Glycol/Dextran Aqueous Two Phase System

PubMed Central

Mehrnoush, Amid; Mustafa, Shuhaimi; Sarker, Md. Zaidul Islam; Yazid, Abdul Manap Mohd

2012-01-01

Mango peel is a good source of protease but remains an industrial waste. This study focuses on the optimization of polyethylene glycol (PEG)/dextran-based aqueous two-phase system (ATPS) to purify serine protease from mango peel. The activity of serine protease in different phase systems was studied and then the possible relationship between the purification variables, namely polyethylene glycol molecular weight (PEG, 4000–12,000 g·mol−1), tie line length (−3.42–35.27%), NaCl (−2.5–11.5%) and pH (4.5–10.5) on the enzymatic properties of purified enzyme was investigated. The most significant effect of PEG was on the efficiency of serine protease purification. Also, there was a significant increase in the partition coefficient with the addition of 4.5% of NaCl to the system. This could be due to the high hydrophobicity of serine protease compared to protein contaminates. The optimum conditions to achieve high partition coefficient (84.2) purification factor (14.37) and yield (97.3%) of serine protease were obtained in the presence of 8000 g·mol−1 of PEG, 17.2% of tie line length and 4.5% of NaCl at pH 7.5. The enzymatic properties of purified serine protease using PEG/dextran ATPS showed that the enzyme could be purified at a high purification factor and yield with easy scale-up and fast processing. PMID:22489172

Optimization of serine protease purification from mango (Mangifera indica cv. Chokanan) peel in polyethylene glycol/dextran aqueous two phase system.

PubMed

Mehrnoush, Amid; Mustafa, Shuhaimi; Sarker, Md Zaidul Islam; Yazid, Abdul Manap Mohd

2012-01-01

Mango peel is a good source of protease but remains an industrial waste. This study focuses on the optimization of polyethylene glycol (PEG)/dextran-based aqueous two-phase system (ATPS) to purify serine protease from mango peel. The activity of serine protease in different phase systems was studied and then the possible relationship between the purification variables, namely polyethylene glycol molecular weight (PEG, 4000-12,000 g·mol(-1)), tie line length (-3.42-35.27%), NaCl (-2.5-11.5%) and pH (4.5-10.5) on the enzymatic properties of purified enzyme was investigated. The most significant effect of PEG was on the efficiency of serine protease purification. Also, there was a significant increase in the partition coefficient with the addition of 4.5% of NaCl to the system. This could be due to the high hydrophobicity of serine protease compared to protein contaminates. The optimum conditions to achieve high partition coefficient (84.2) purification factor (14.37) and yield (97.3%) of serine protease were obtained in the presence of 8000 g·mol(-1) of PEG, 17.2% of tie line length and 4.5% of NaCl at pH 7.5. The enzymatic properties of purified serine protease using PEG/dextran ATPS showed that the enzyme could be purified at a high purification factor and yield with easy scale-up and fast processing.

Effect of polyethelene oxide on the thermal degradation of cellulose biofilm – Low cost material for soft tissue repair in dentistry

PubMed Central

Tyler, Rakim; Schiraldi, David; Roperto, Renato; Faddoul, Fady; Teich, Sorin

2017-01-01

Background Bio cellulose is a byproduct of sweet tea fermentation known as kombusha. During the biosynthesis by bacteria cellulose chains are polymerized by enzyme from activated glucose. The single chains are then extruded through the bacterial cell wall. Interestingly, a potential of the Kombucha’s byproduct bio cellulose (BC) as biomaterial had come into focus only in the past few decades. The unique physical and mechanical properties such as high purity, an ultrafine and highly crystalline network structure, a superior mechanical strength, flexibility, pronounced permeability to gases and liquids, and an excellent compatibility with living tissue that reinforced by biodegradability, biocompatibility, large swelling ratios. Material and Methods The bio-cellulose film specimens were provided by the R.P Dressel dental materials laboratory, Department of Comprehensive Care, School of Dental Medicine, Case Western Reserve University, Cleveland, US. The films were harvested, washed with water and dried at room temperature overnight. 1wt% of PEG-2000 and 10wt% of NaOH were added into ultrapure water to prepare PEG/NaOH solution. Then bio-cellulose film was added to the mixture and swell for 3 h at room temperature. All bio-cellulose film specimens were all used in the TA Instruments Q500 Thermogravmetric Analyzer to investigate weight percent lost and degradation. The TGA was under ambient air conditions at a heating rate of 10ºC/min. Results and Conclusions PEG control exhibited one transition with the peak at 380ºC. Cellulose and cellulose/ PEG films showed 3 major transitions. Interestingly, the cellulose/PEG film showed slightly elevated temperatures when compared to the corresponding transitions for cellulose control. The thermal gravimetric analysis (TGA) degradation curves were analyzed. Cellulose control film exhibited two zero order transitions, that indicate the independence of the rate of degradation from the amount on the initial substance. The activation energies for three transitions for cellulose and cellulose/PEG showed increasingly higher values for the transitions at higher temperatures. Key words:TGA, Bio-cellulose, PEG. PMID:28828153

Poly(ethylene glycol) (PEG)-lactic acid nanocarrier-based degradable hydrogels for restoring the vaginal microenvironment

PubMed Central

Rajan, Sujata Sundara; Turovskiy, Yevgeniy; Singh, Yashveer; Chikindas, Michael L.; Sinko, Patrick J.

2014-01-01

Women with bacterial vaginosis (BV) display reduced vaginal acidity, which make them susceptible to associated infections such as HIV. In the current study, poly(ethylene glycol) (PEG) nanocarrier-based degradable hydrogels were developed for the controlled release of lactic acid in the vagina of BV-infected women. PEG-lactic acid (PEG-LA) nanocarriers were prepared by covalently attaching lactic acid to 8-arm PEG-SH via cleavable thioester bonds. PEG-LA nanocarriers with 4 copies of lactic acid per molecule provided controlled release of lactic acid with a maximum release of 23% and 47% bound lactic acid in phosphate buffered saline (PBS, pH 7.4) and acetate buffer (AB, pH 4.3), respectively. The PEG nanocarrier-based hydrogels were formed by cross-linking the PEG-LA nanocarriers with 4-arm PEG-NHS via degradable thioester bonds. The nanocarrier-based hydrogels formed within 20 min under ambient conditions and exhibited an elastic modulus that was 100-fold higher than the viscous modulus. The nanocarrier-based degradable hydrogels provided controlled release of lactic acid for several hours; however, a maximum release of only 10%–14% bound lactic acid was observed possibly due to steric hindrance of the polymer chains in the cross-linked hydrogel. In contrast, hydrogels with passively entrapped lactic acid showed burst release with complete release within 30 min. Lactic acid showed antimicrobial activity against the primary BV pathogen Gardnerella vaginalis with a minimum inhibitory concentration (MIC) of 3.6 mg/ml. In addition, the hydrogels with passively entrapped lactic acid showed retained antimicrobial activity with complete inhibition G. vaginalis growth within 48 h. The results of the current study collectively demonstrate the potential of PEG nanocarrier-based hydrogels for vaginal administration of lactic acid for preventing and treating BV. PMID:25223229

Adsorption of poly(ethylene glycol)-modified ribonuclease A to a poly(lactide-co-glycolide) surface.

PubMed

Daly, Susan M; Przybycien, Todd M; Tilton, Robert D

2005-06-30

Protein adsorption is a source of variability in the release profiles of therapeutic proteins from biodegradable microspheres. We employ optical reflectometry and total internal reflection fluorescence to explore the extent and kinetics of ribonuclease A (RNase A) adsorption to spin-cast films of poly(lactide-co-glycolide) (PLG) and, in particular, to determine how covalent grafting of polyethylene glycol (PEG) to RNase A affects adsorption. Adsorption kinetics on PLG surfaces are surface-limited for RNase A but transport-limited for unconjugated PEG homopolymers and for PEG-modified RNase A, indicating that PEG anchors the conjugates to the surface during the transport-limited regime. PEG modification of RNase A decreases the total number of adsorbed molecules per unit area but increases the areal surface coverage because the grafted PEG chains exclude additional surface area. Total internal reflection fluorescence-based exchange measurements show that there is no exchange between adsorbed and solution-phase protein molecules. This indicates an unusually tenacious adsorption. Streaming current measurements indicate that the zeta potential of the PLG surface becomes increasingly negative as the film is exposed to water for several weeks, as expected. Aging of the PLG surface results in increased adsorption of unmodified RNase A but decreased adsorption of unconjugated PEG homopolymers and of PEG-RNase A conjugates, relative to the extent of adsorption on freshly prepared PLG surfaces. Adsorption results correlate well with an increase in the rate, total extent and preservation of bioactivity of RNase A released from PLG microspheres for the PEG-modified version of RNase A.

The molar hydrodynamic volume changes of factor VIIa due to GlycoPEGylation.

PubMed

Plesner, Bitten; Westh, Peter; Hvidt, Søren; Nielsen, Anders D

2011-06-01

The effects of GlycoPEGylation on the molar hydrodynamic volume of recombinant human rFVIIa were investigated using rFVIIa and two GlycoPEGylated recombinant human FVIIa derivatives, a linear 10kDa PEG and a branched 40kDa PEG, respectively. Molar hydrodynamic volumes were determined by capillary viscometry and mass spectrometry. The intrinsic viscosities of rFVIIa, its two GlycoPEGylated compounds, and of linear 8kDa, 10kDa, 20kDa and branched 40kDa PEG polymers were determined. The measured intrinsic viscosity of rFVIIa is 6.0mL/g, while the intrinsic viscosities of 10kDa PEG-rFVIIa and 40kDa PEG-rFVIIa are 29.5mL/g and 79.0mL/g, respectively. The intrinsic viscosities of the linear PEG polymers are 20, 22.6 and 41.4mL/g for 8, 10, and 20kDa, respectively, and 61.1mL/g for the branched 40kDa PEG. From the results of the intrinsic viscosity and MALDI-TOF measurements it is evident, that the molar hydrodynamic volume of the conjugated protein is not just an addition of the molar hydrodynamic volume of the PEG and the protein. The molar hydrodynamic volume of the GlycoPEGylated protein is larger than the volume of its composites. These results suggest that both the linear and the branched PEG are not wrapped around the surface of rFVIIa but are chains that are significantly stretched out when attached to the protein. Copyright © 2011 Elsevier B.V. All rights reserved.

Design and Validation of PEG-Derivatized Vitamin E Copolymer for Drug Delivery into Breast Cancer.

PubMed

Li, Yanping; Liu, Qinhui; Li, Wenyao; Zhang, Ting; Li, Hanmei; Li, Rui; Chen, Lei; Pu, Shiyun; Kuang, Jiangying; Su, Zhiguang; Zhang, Zhirong; He, Jinhan

2016-08-17

This study examined the ability of amphiphilic poly(ethylene glycol) (PEG) derivatives to assemble into micelles for drug delivery. Linear PEG chains were modified on one end with hydrophobic vitamin E succinate (VES), and PEG and VES were mixed in different molar ratios to make amphiphiles, which were characterized in terms of critical micelle concentration (CMC), drug loading capacity (DLC), serum stability, tumor spheroid penetration and tumor targeting in vitro and in vivo. The amphiphile PEG5K-VES6 (PAMV6), which has a wheat-like structure, showed a CMC of 3.03 × 10(-6) M, good serum stability, and tumor accumulation. The model drug, pirarubicin (THP), could be efficiently loaded into PAMV6 micelles at a DLC of 24.81%. PAMV6/THP micelles were more effective than THP solution at inducing cell apoptosis and G2/M arrest in 4T1 cells. THP-loaded PAMV6 micelles also inhibited tumor growth much more than free THP in a syngeneic mouse model of breast cancer. PAMV6-based micellar systems show promise as nanocarriers for improved anticancer chemotherapy.

Conformational effects on cationization of poly(ethylene glycol) by alkali metal ions in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

NASA Astrophysics Data System (ADS)

Shimada, Kayori; Matsuyama, Shigetomo; Saito, Takeshi; Kinugasa, Shinichi; Nagahata, Ritsuko; Kawabata, Shin-Ichirou

2005-12-01

Conformational effects of polymer chains on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) were studied by using an equimolar mixture of uniform poly(ethylene glycol)s (PEGs) and by molecular dynamics simulations. Uniform PEGs with degrees of polymerization n = 8-39 were separated from commercial PEG samples by preparative supercritical fluid chromatography. MALDI-TOFMS spectra of an equimolar mixture of the uniform PEGs in aqueous ethanol were measured by adding a mixture of 2,5-dihydroxybenzoic acid (as a matrix reagent) and five alkali metal chlorides (LiCl, NaCl, KCl, RbCl, and CsCl). After optimization of the matrix concentration and laser power, five types of adduct cationized by Li+, Na+, K+, Rb+, and Cs+ could be identified simultaneously in the same spectrum. In the lower molecular-mass region around 103, the spectral intensity increase rapidly with increasing molecular mass of PEG; this rapid increase in the spectral intensity started at a lower molecular mass for smaller adduct cations. Molecular dynamics simulations were used to calculated the affinity of PEG for the adduct cations. These experimental and simulated results showed that the observed spectral intensities in MALDI-TOFMS were markedly affected by the species of adduct cations and the degree of polymerization of the PEG, and that they were dependent on the stability of the PEG-cation complex.

PEG-based degradable networks for drug delivery applications

NASA Astrophysics Data System (ADS)

Ostroha, Jamie L.

The controlled delivery of therapeutic agents by biodegradable hydrogels has become a popular mechanism for drug administration in recent years. Hydrogels are three-dimensional networks of polymer chains held together by crosslinks. Although the changes which the hydrogel undergoes in solution are important to a wide range of experimental studies, they have not been investigated systematically and the factors which influence the degree of swelling have not been adequately described. Hydrogels made of poly(ethylene glycol) (PEG) will generally resist degradation in aqueous conditions, while a hydrogel made from a copolymer of poly(lactic acid) (PLA) and PEG will degrade via hydrolysis of the lactic acid group. This ability to degrade makes these hydrogels promising candidates for controlled release drug delivery systems. The goal of this research was to characterize the swelling and degradation of both degradable and non-degradable gels and to evaluate the release of different drugs from these hydrogels, where the key variable is the molecular weight of the PEG segment. These hydrogels were formed by the addition and subsequent chemically crosslinking of methacrylate end groups. During crosslinking, both PEG and LA-PEG-LA hydrogels of varied PEG molecular weight were loaded with Vitamin B12, Insulin, Haloperidol, and Dextran. It was shown that increasing PEG molecular weight produces a hydrogel with larger pores, thus increasing water uptake and degradation rate. While many environmental factors do not affect the swelling behavior, they do significantly impact the degradation of the hydrogel, and thus the release of incorporated therapeutic agents.

PEG-b-PCL polymeric nano-micelle inhibits vascular angiogenesis by activating p53-dependent apoptosis in zebrafish

PubMed Central

Zhou, Tian; Dong, Qinglei; Shen, Yang; Wu, Wei; Wu, Haide; Luo, Xianglin; Liao, Xiaoling; Wang, Guixue

2016-01-01

Micro/nanoparticles could cause adverse effects on cardiovascular system and increase the risk for cardiovascular disease-related events. Nanoparticles prepared from poly(ethylene glycol) (PEG)-b-poly(ε-caprolactone) (PCL), namely PEG-b-PCL, a widely studied biodegradable copolymer, are promising carriers for the drug delivery systems. However, it is unknown whether polymeric PEG-b-PCL nano-micelles give rise to potential complications of the cardiovascular system. Zebrafish were used as an in vivo model to evaluate the effects of PEG-b-PCL nano-micelle on cardiovascular development. The results showed that PEG-b-PCL nano-micelle caused embryo mortality as well as embryonic and larval malformations in a dose-dependent manner. To determine PEG-b-PCL nano-micelle effects on embryonic angiogenesis, a critical process in zebrafish cardiovascular development, growth of intersegmental vessels (ISVs) and caudal vessels (CVs) in flk1-GFP transgenic zebrafish embryos using fluorescent stereomicroscopy were examined. The expression of fetal liver kinase 1 (flk1), an angiogenic factor, by real-time quantitative polymerase chain reaction (qPCR) and in situ whole-mount hybridization were also analyzed. PEG-b-PCL nano-micelle decreased growth of ISVs and CVs, as well as reduced flk1 expression in a concentration-dependent manner. Parallel to the inhibitory effects on angiogenesis, PEG-b-PCL nano-micelle exposure upregulated p53 pro-apoptotic pathway and induced cellular apoptosis in angiogenic regions by qPCR and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assay. This study further showed that inhibiting p53 activity, either by pharmacological inhibitor or RNA interference, could abrogate the apoptosis and angiogenic defects caused by PEG-b-PCL nano-micelles, indicating that PEG-b-PCL nano-micelle inhibits angiogenesis by activating p53-mediated apoptosis. This study indicates that polymeric PEG-b-PCL nano-micelle could pose potential hazards to cardiovascular development. PMID:27980407

PEG-b-PCL polymeric nano-micelle inhibits vascular angiogenesis by activating p53-dependent apoptosis in zebrafish.

PubMed

Zhou, Tian; Dong, Qinglei; Shen, Yang; Wu, Wei; Wu, Haide; Luo, Xianglin; Liao, Xiaoling; Wang, Guixue

Micro/nanoparticles could cause adverse effects on cardiovascular system and increase the risk for cardiovascular disease-related events. Nanoparticles prepared from poly(ethylene glycol) (PEG)- b -poly( ε -caprolactone) (PCL), namely PEG- b -PCL, a widely studied biodegradable copolymer, are promising carriers for the drug delivery systems. However, it is unknown whether polymeric PEG- b -PCL nano-micelles give rise to potential complications of the cardiovascular system. Zebrafish were used as an in vivo model to evaluate the effects of PEG- b -PCL nano-micelle on cardiovascular development. The results showed that PEG- b -PCL nano-micelle caused embryo mortality as well as embryonic and larval malformations in a dose-dependent manner. To determine PEG- b -PCL nano-micelle effects on embryonic angiogenesis, a critical process in zebrafish cardiovascular development, growth of intersegmental vessels (ISVs) and caudal vessels (CVs) in flk1-GFP transgenic zebrafish embryos using fluorescent stereomicroscopy were examined. The expression of fetal liver kinase 1 (flk1), an angiogenic factor, by real-time quantitative polymerase chain reaction (qPCR) and in situ whole-mount hybridization were also analyzed. PEG- b -PCL nano-micelle decreased growth of ISVs and CVs, as well as reduced flk1 expression in a concentration-dependent manner. Parallel to the inhibitory effects on angiogenesis, PEG- b -PCL nano-micelle exposure upregulated p53 pro-apoptotic pathway and induced cellular apoptosis in angiogenic regions by qPCR and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assay. This study further showed that inhibiting p53 activity, either by pharmacological inhibitor or RNA interference, could abrogate the apoptosis and angiogenic defects caused by PEG- b -PCL nano-micelles, indicating that PEG- b -PCL nano-micelle inhibits angiogenesis by activating p53-mediated apoptosis. This study indicates that polymeric PEG- b -PCL nano-micelle could pose potential hazards to cardiovascular development.

Chitosan-g-MPEG-modified alginate/chitosan hydrogel microcapsules: a quantitative study of the effect of polymer architecture on the resistance to protein adsorption.

PubMed

Zheng, Jia N; Xie, Hong G; Yu, Wei T; Liu, Xiu D; Xie, Wei Y; Zhu, Jing; Ma, Xiao J

2010-11-16

The chemical modification of the alginate/chitosan/alginate (ACA) hydrogel microcapsule with methoxy poly(ethylene glycol) (MPEG) was investigated to reduce nonspecific protein adsorption and improve biocompatibility in vivo. The graft copolymer chitosan-g-MPEG (CS-g-MPEG) was synthesized, and then alginate/chitosan/alginate/CS-g-MPEG (ACAC(PEG)) multilayer hydrogel microcapsules were fabricated by the layer-by-layer (LBL) polyelectrolyte self-assembly method. A quantitative study of the modification was carried out by the gel permeation chromatography (GPC) technique, and protein adsorption on the modified microcapsules was also investigated. The results showed that the apparent graft density of the MPEG side chain on the microcapsules decreased with increases in the degree of substitution (DS) and the MPEG chain length. During the binding process, the apparent graft density of CS-g-MPEG showed rapid growth-plateau-rapid growth behavior. CS-g-MPEG was not only bound to the surface but also penetrated a certain depth into the microcapsule membranes. The copolymers that penetrated the microcapsules made a smaller contribution to protein repulsion than did the copolymers on the surfaces of the microcapsules. The protein repulsion ability decreased with the increase in DS from 7 to 29% with the same chain length of MPEG 2K. CS-g-MPEG with MPEG 2K was more effective at protein repulsion than CS-g-MPEG with MPEG 550, having a similar DS below 20%. In this study, the microcapsules modified with CS-g-MPEG2K-DS7% had the lowest IgG adsorption of 3.0 ± 0.6 μg/cm(2), a reduction of 61% compared to that on the chitosan surface.

Synthesis and characterization of biodegradable poly (ethylene glycol) and poly (caprolactone diol) end capped poly (propylene fumarate) cross linked amphiphilic hydrogel as tissue engineering scaffold material.

PubMed

Krishna, Lekshmi; Jayabalan, Muthu

2009-12-01

Biodegradable poly (caprolactone diol-co-propylene fumarate-co-ethylene glycol) amphiphilic polymer with poly (ethylene glycol) and poly (caprolactone diol) chain ends (PCL-PPF-PEG) was prepared. PCL-PPF-PEG undergoes fast setting with acrylamide (aqueous solution) by free radical polymerization and produces a crosslinked hydrogel. The cross linked and freeze-dried amphiphilic material has porous and interconnected network. It undergoes higher degree of swelling and water absorption to form hydrogel with hydrophilic and hydrophobic domains at the surface and appreciable tensile strength. The present hydrogel is compatible with L929 fibroblast cells. PCL-PPF-PEG/acrylamide hydrogel is a candidate scaffold material for tissue engineering applications.

Irradiation Induced Fluorescence Enhancement in PEGylated Cyanine-based NIR Nano- and Meso-scale GUMBOS

PubMed Central

Lu, Chengfei; Das, Susmita; Magut, Paul K. S.; Li, Min; El Zahab, Bilal; Warner, Isiah M.

2014-01-01

We report on the synthesis and characterization of a PEGylated IR786 GUMBOS (Group of Uniform Materials Based on Organic Salts). The synthesis of this material was accomplished using a three step protocol: (1) substitution of chloride on the cyclohexenyl ring in the heptamethine chain of IR786 by 6-aminohexanoic acid, (2) grafting of methoxy poly ethyleneglycol (MeOPEG) onto the 6-aminohexanoic acid via an esterification reaction, and (3) anion exchange between [PEG786][I] and lithium bis(trifluoromethylsulfonyl)imide (LiNTf2) or sodium bis(2-ethylhexyl)sulfosuccinate (AOT) in order to obtain PEG786 GUMBOS. Examination of spectroscopic data for this PEG786 GUMBOS indicates a large stokes shift (122 nm). It was observed that this PEG786 GUMBOS associates in aqueous solution to form nano-and meso-scale self-assemblies with sizes ranging from 100 to 220 nm. These nano- and meso-scale GUMBOS are also able to resist nonspecific binding to proteins. PEGylation of the original IR786 leads to reduced cytotoxicity. In addition, it was noted that anions, such as NTf2 and AOT, play a significant role in improving the photostability of PEG786 GUMBOS. Irradiation-induced J aggregation in [PEG786][NTf2] and to some extent in [PEG786][AOT] produced enhanced photostability. This observation was supported by use of both steady state and time-resolved fluorescence measurements. PMID:22957476

Biomaterials differentially regulate Src kinases and phosphoinositide 3-kinase-γ in polymorphonuclear leukocyte primary and tertiary granule release

PubMed Central

Cohen, Hannah Caitlin; Frost, Dustin C.; Lieberthal, Tyler Jacob; Li, Lingjun; Kao, W. John

2018-01-01

In the foreign body response, infiltrating PMNs exocytose granule subsets to influence subsequent downstream inflammatory and wound healing events. In previous studies, we found that PMNs cultured on poly(ethylene glycol) (PEG)-containing hydrogels (i.e., PEG and gelatin + PEG hydrogels) had enhanced primary granule release, yet similar tertiary granule release compared with PMNs cultured on polydimethylsiloxane or tissue culture polystyrene. PMN primary granules contain microbicidal proteins and proteases, which can potentially injure bystander cells, degrade the extracellular matrix, and promote inflammation. Here, we sought to understand the mechanism of the enhanced primary granule release from PMNs on PEG hydrogels. We found that primary granule release from PMNs on PEG hydrogels was adhesion mediated and involved Src family kinases and PI3K-γ. The addition of gelatin to PEG hydrogels did not further enhance PMN primary granule release. Using stable-isotope dimethyl labeling-based shotgun proteomics, we identified many serum proteins – including Ig gamma constant chain region proteins and alpha-1-acid glycoprotein 1 – that were absorbed/adsorbed in higher quantities on PEG hydrogels than on TCPS, and may be involved in mediating PMN primary granule release. Ultimately, this mechanistic knowledge can be used to direct inflammation and wound healing following biomaterial implantation to promote a more favorable healing response. PMID:25736495

Modeling of nanoparticle coatings for medical applications

NASA Astrophysics Data System (ADS)

Haume, Kaspar; Mason, Nigel J.; Solov'yov, Andrey V.

2016-09-01

Gold nanoparticles (AuNPs) have been shown to possess properties beneficial for the treatment of cancerous tumors by acting as radiosensitizers for both photon and ion radiation. Blood circulation time is usually increased by coating the AuNPs with poly(ethylene glycol) (PEG) ligands. The effectiveness of the PEG coating, however, depends on both the ligand surface density and length of the PEG molecules, making it important to understand the structure of the coating. In this paper the thickness, ligand surface density, and density of the PEG coating is studied with classical molecular dynamics using the software package MBN Explorer. AuNPs consisting of 135 atoms (approximately 1.4 nm diameter) in a water medium have been studied with the number of PEG ligands varying between 32 and 60. We find that the thickness of the coating is only weakly dependent on the surface ligand density and that the degree of water penetration is increased when there is a smaller number of attached ligands.

Ion-Specific Interfacial Crystallization of Polymer-Grafted Nanoparticles

DOE PAGES

Zhang, Honghu; Wang, Wenjie; Mallapragada, Surya; ...

2017-06-27

In this study, ion-specific effects on the assembly and crystallization of polyethylene-glycol-grafted Au nanoparticles (PEG-AuNPs) at the vapor–liquid interface are examined by surface sensitive synchrotron X-ray scattering methods. We show that monovalent salts, such as KCl and NaCl, that do not advance phase separation of pure PEG at room temperature induce two-dimensional (2D) self-assembly and crystallization of PEG-AuNPs with some distinctions. Whereas for KCl the 2D hexagonal coherence length of the PEG-AuNP superlattices is remarkably large compared to other salts (over micron-sized crystalline grains), NaCl induces coexistence of two hexagonal structures. Using various salts, we find that the value ofmore » the lattice constant is correlated to the ionic hydration entropy consistent with the Hofmeister series.« less

A poly(alkyl methacrylate-divinylbenzene-vinylbenzyl trimethylammonium chloride) monolithic column for solid-phase microextraction.

PubMed

Liu, Wan-Ling; Lirio, Stephen; Yang, Yicong; Wu, Lin-Tai; Hsiao, Shu-Ying; Huang, Hsi-Ya

2015-05-22

In this study, an organic polymer monolithic columns, which were prepared via in situ polymerization of alkyl methacrylate-ester (AMA), divinylbenzene (DVB) and vinylbenzyl trimethylammonium chloride (VBTA, charged monomer), were developed as adsorbent for solid-phase microextraction (SPME). Different parameters affecting the extraction efficiency for nine (9) non-steroidal anti-inflammatory drugs (NSAIDs) such as the ratio of the stearyl methacrylate (SMA) to DVB monomer, column length, sample pH, extraction flow rate and desorption solvent were investigated to obtain the optimal SPME condition. Also, the permeability for each poly(AMA-DVB-VBTA) monolithic column was investigated by adding porogenic solvent (poly(ethylene glycol), PEG). Using the optimized condition, a series of AMA-based poly(AMA-DVB-VBTA) monolith columns were developed to determine the effect the extraction efficiency of NSAIDs by varying the alkyl chain length of the methacrylate ester (methyl-, butyl-, octyl-, or lauryl-methacrylate; (MMA, BMA, OMA, LMA)). Results showed that decreasing the AMA chain length increases the extraction efficiency of some NSAIDs (i.e. sulindac (sul), naproxen (nap), ketoprofen (ket) and indomethacin (idm)). Among the poly(AMA-DVB-VBTA) monolithic columns, poly(BMA-DVB-VBTA) showed a highly repeatable extraction efficiency for NSAIDs with recoveries ranging from 85.0 to 100.2% with relative standard deviation (RSD) less than 6.8% (n=3). The poly(BMA-DVB-VBTA) can also be reused for at least 50 times without any significant effect in extraction efficiency for NSAIDs. Finally, using the established conditions, the poly(BMA-DVB-VBTA) was used to extract trace-level NSAIDs (100μgL(-1)) in river water with good recoveries ranging from 75.8 to 90.8% (RSD<14.9%). Copyright © 2015 Elsevier B.V. All rights reserved.

A colorimetric method for the molecular weight determination of polyethylene glycol using gold nanoparticles

PubMed Central

2013-01-01

A gold nanoparticle (AuNP)-based colorimetric method was developed for the molecular weight (MW) determination of polyethylene glycol (PEG), a commonly used hydrophilic polymer. Addition of a salt solution to PEG-coated AuNP solutions helps in screening the electrostatic repulsion between nanoparticles and generating a color change of the solutions from wine red to blue in 10 min in accordance with the MW of PEG, which illustrates the different stability degrees (SDs) of the AuNPs. The SDs are calculated by the absorbance ratios of the stable to the aggregated AuNPs in the solution. The root mean square end-to-end length (〈h2〉1/2) of PEG molecules shows a linear fit to the SDs of the PEG-coated AuNPs in a range of 1.938 ± 0.156 to 10.151 ± 0.176 nm. According to the Derjaguin-Landau-Verwey-Overbeek theory, the reason for this linear relationship is that the thickness of the PEG adlayer is roughly equivalent to the 〈h2〉1/2 of the PEG molecules in solution, which determines the SDs of the AuNPs. Subsequently, the MW of the PEG can be obtained from its 〈h2〉1/2 using a mathematical relationship between 〈h2〉1/2 and MW of PEG molecule. Applying this approach, we determined the 〈h2〉1/2 and the MW of four PEG samples according to their absorbance values from the ordinary ultraviolet–visible spectrophotometric measurements. Therefore, the MW of PEG can be distinguished straightforwardly by visual inspection and determined by spectrophotometry. This novel approach is simple, rapid, and sensitive. PMID:24359120

Interactions between carbamazepine and polyethylene glycol (PEG) 6000: characterisations of the physical, solid dispersed and eutectic mixtures.

PubMed

Naima, Z; Siro, T; Juan-Manuel, G D; Chantal, C; René, C; Jerome, D

2001-02-01

The influence of a hydrophilic carrier (PEG 6000) on the polymorphism of carbamazepine, an antiepileptic drug, was investigated in binary physical mixtures and solid dispersions by means of differential scanning calorimetry (DSC), thermal gravimetry, hot-stage microscopy (HSM), and X-ray diffractometry, respectively. This study provides also an attempt to develop a method to calculate more precisely the eutectic composition. In rather ideal physical mixtures, carbamazepine was found as monoclinic Form III. In solid dispersions, the drug was found to crystallize as trigonal Form II; a eutectic invariant in the PEG 6000-rich composition domain (6% of carbamazepine mass) was evidenced by DSC experiments and confirmed by HSM observations. In the binary phase diagram the ideal carbamazepine liquidus curve was located at temperatures higher than the respective experimental ones. This suggests that drug can be maintained in the liquid state in the temperature-mass fraction (T--x) region between the two carbamazepine liquidus curves. This indicates in turn that attractive interactions occur between carbamazepine and PEG 6000-chains. These interactions have been also claimed to prevent carbamazepine from degradation into iminostilbene (a compound resulting from the chemical degradation of carbamazepine which is postulated to be responsible for the idiosyncratic toxicity of the drug) and thought to lead to the crystallization of metastable Carbamazepine II from melt. The negative excess entropy for eutectic mixtures indicated that the drug crystals are finely dispersed in the bulk of polymer chains.

Ionic liquid-based aqueous biphasic systems as a versatile tool for the recovery of antioxidant compounds.

PubMed

Santos, João H; e Silva, Francisca A; Ventura, Sónia P M; Coutinho, João A P; de Souza, Ranyere L; Soares, Cleide M F; Lima, Álvaro S

2015-01-01

The comparative evaluation of distinct types of ionic liquid-based aqueous biphasic systems (IL-ABS) and more conventional polymer/salt-based ABS to the extraction of two antioxidants, eugenol and propyl gallate, is focused. In a first approach, IL-ABS composed of ILs and potassium citrate (C6H5K3O7/C6H8O7) buffer at pH 7 were applied to the extraction of two antioxidants, enabling the assessment of the impact of IL cation core on the extraction. The second approach uses ABS composed of polyethylene glycol (PEG) and potassium phosphate (K2HPO4/KH2PO4) buffer at pH 7 with imidazolium-based ILs as adjuvants. Their application to the extraction of the compounds allowed the investigation of the impact of the presence/absence of IL, the PEG molecular weight, and the alkyl side chain length of the imidazolium cation on the partition. It is possible to maximize the extractive performance of both antioxidants up to 100% using both types of IL-ABS. The IL enhances the performance of ABS technology. The data puts in evidence the pivotal role of the appropriate selection of the ABS components and design to develop a successful extractive process, from both environmental and performance points of view. © 2014 American Institute of Chemical Engineers.

Biodistribution and toxicological study of PEGylated single-wall carbon nanotubes in the zebrafish (Danio rerio) nervous system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weber, Gisele E.B.; Dal Bosco, Lidiane; Programa de Pós-graduação em Ciências Fisiológicas–Fisiologia Animal Comparada, FURG, Rio Grande, RS, 96210-900

Nanotechnology has been proven to be increasingly compatible with pharmacological and biomedical applications. Therefore, we evaluated the biological interactions of single-wall carbon nanotubes functionalized with polyethylene glycol (SWNT-PEG). For this purpose, we analyzed biochemical, histological, behavioral and biodistribution parameters to understand how this material behaves in vitro and in vivo using the fish Danio rerio (zebrafish) as a biological model. The in vitro results for fish brain homogenates indicated that SWNT-PEG had an effect on lipid peroxidation and GSH (reduced glutathione) content. However, after intraperitoneal exposure, SWNT-PEG proved to be less biocompatible and formed aggregates, suggesting that the PEG usedmore » for the nanoparticle functionalization was of an inappropriate size for maintaining product stability in a biological environment. This problem with functionalization may have contributed to the low or practically absent biodistribution of SWNT-PEG in zebrafish tissues, as verified by Raman spectroscopy. There was an accumulation of material in the abdominal cavity that led to inflammation and behavioral disturbances, as evaluated by a histological analysis and an open field test, respectively. These results provide evidence of a lack of biocompatibility of SWNTs modified with short chain PEGs, which leads to the accumulation of the material, tissue damage and behavioral alterations in the tested subjects. - Highlights: • In vitro brain exposure diminished lipid peroxidation. • In vitro brain exposure depletes the GSH content. • SWNT-PEG was not biocompatible and formed aggregates after the exposure. • Practically absent biodistribution of SWNT-PEG was observed by Raman spectroscopy. • SWNT-PEG exposure lead to tissue damage and inflammatory responses.« less

Mass Spectrometry of Single Particles Levitated in an Electrodynamic Balance: Applications to Laboratory Atmospheric Chemistry Research

NASA Astrophysics Data System (ADS)

Birdsall, A.; Krieger, U. K.; Keutsch, F. N.

2017-12-01

Dynamic changes to atmospheric aerosol particle composition (e.g., originating from evaporation/condensation, oxidative aging, or aqueous-phase chemical reactions) impact particle properties with importance for understanding particle effects on climate and human health. These changes can take place over the entire lifetime of an atmospheric particle, which can extend over multiple days. Previous laboratory studies of such processes have included analyzing single particles suspended in a levitation device, such as an electrodynamic balance (EDB), an optical levitator, or an acoustic trap, using optical detection techniques. However, studying chemically complex systems can require an analytical method, such as mass spectrometry, that provides more molecular specificity. Existing work coupling particle levitation with mass spectrometry is more limited and largely has consisted of acoustic levitation of millimeter-sized droplets.In this work an EDB has been coupled with a custom-built ionization source and commercial time-of-flight mass spectrometer (MS) as a platform for laboratory atmospheric chemistry research. Single charged particles (radius 10 μm) have been injected into an EDB, levitated for an arbitrarily long period of time, and then transferred to a vaporization-corona discharge ionization region for MS analysis. By analyzing a series of particles of identical composition, residing in the controlled environment of the EDB for varying times, we can trace the chemical evolution of a particle over hours or days, appropriate timescales for understanding transformations of atmospheric particles.To prove the concept of our EDB-MS system, we have studied the evaporation of particles consisting of polyethylene glycol (PEG) molecules of mixed chain lengths, used as a benchmark system. Our system can quantify the composition of single particles (see Figure for sample spectrum of a single PEG-200 particle: PEG parent ions labeled with m/z, known PEG fragment ions labeled with *). Furthermore, our measured evaporation rates are consistent with a kinetic model. We will discuss future types of experiments enabled by EDB-MS, by allowing detailed chemical changes of a particle in a controlled laboratory environment to be monitored on timescales mimicking those of particles in the atmosphere.

Membrane lateral compressibility determined by NMR and x-ray diffraction: effect of acyl chain polyunsaturation.

PubMed Central

Koenig, B W; Strey, H H; Gawrisch, K

1997-01-01

The elastic area compressibility modulus, Ka, of lamellar liquid crystalline bilayers was determined by a new experimental approach using 2H-NMR order parameters of lipid hydrocarbon chains together with lamellar repeat spacings measured by x-ray diffraction. The combination of NMR and x-ray techniques yields accurate determination of lateral area per lipid molecule. Samples of saturated, monounsaturated, and polyunsaturated phospholipids were equilibrated with polyethylene glycol (PEG) 20,000 solutions in water at concentrations from 0 to 55 wt % PEG at 30 degrees C. This procedure is equivalent to applying 0 to 8 dyn/cm lateral pressure to the bilayers. The resulting reductions in area per lipid were measured with a resolution of +/-0.2 A2 and the fractional area decrease was proportional to applied lateral pressure. For 1,2-dimyristoyl(d54)-sn-glycero-3-phosphocholine, 1-stearoyl(d35)-2-oleoyl-sn-glycero-3-phosphocholine (SOPC-d35), and 1-stearoyl(d35)-2-docosahexaenoyl-sn-glycero-3-phosphocholine (SDPC-d35) cross-sectional areas per molecule in excess water of 59.5, 61.4, and 69.2 A2 and bilayer elastic area compressibility moduli of 141, 221, and 121 dyn/cm were determined, respectively. Combining NMR and x-ray results enables the determination of compressibility differences between saturated and unsaturated hydrocarbon chains. In mixed-chain SOPC-d35 both chains have similar compressibility moduli; however, in mixed-chain polyunsaturated SDPC-d35, the saturated stearic acid chain appears to be far less compressible than the polyunsaturated docosahexaenoic acid chain. Images FIGURE 3 FIGURE 5 PMID:9336191

Target-specific cellular uptake of PLGA nanoparticles coated with poly(L-lysine)-poly(ethylene glycol)-folate conjugate.

PubMed

Kim, Sun Hwa; Jeong, Ji Hoon; Chun, Ki Woo; Park, Tae Gwan

2005-09-13

Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles with anionic surface charge were surface coated with cationic di-block copolymer, poly(L-lysine)-poly(ethylene glycol)-folate (PLL-PEG-FOL) conjugate, for enhancing their site-specific intracellular delivery against folate receptor overexpressing cancer cells. The PLGA nanoparticles coated with the conjugate were characterized in terms of size, surface charge, and change in surface composition by XPS. By employing the flow cytometry method and confocal image analysis, the extent of cellular uptake was comparatively evaluated under various conditions. PLL-PEG-FOL coated PLGA nanoparticles demonstrated far greater extent of cellular uptake to KB cells, suggesting that they were mainly taken up by folate receptor-mediated endocytosis. The enhanced cellular uptake was also observed even in the presence of serum proteins, possibly due to the densely seeded PEG chains. The PLL-PEG-FOL coated PLGA nanoparticles could be potentially applied for cancer cell targeted delivery of various therapeutic agents.

Microcalorimetric study of the adsorption of PEGylated lysozyme and PEG on a mildly hydrophobic resin: influence of ammonium sulfate.

PubMed

Werner, Albert; Blaschke, Tim; Hasse, Hans

2012-08-07

Adsorption of native as well as mono-, di-, and tri-PEGylated lysozyme on Toyopearl PPG-600M, a mildly hydrophobic resin is studied by isothermal titration calorimetry and by independent adsorption equilibrium measurements in sodium phosphate buffer at pH 7.0 and 25 °C. For PEGylation two different PEG sizes are used (5 and 10 kDa) which leads to six different forms of PEGylated lysozyme all of which are systematically studied. Additionally, the adsorption of five pure PEGs is explored. The ammonium sulfate concentration is varied from 600 to 1200 mM. The molar enthalpy of adsorption Δh(p)(ads) is determined from the calorimetric and the adsorption equilibrium data. It is found to be endothermic in all experiments. The comparison of the adsorption of different PEGylated forms shows that the adsorption of PEGylated lysozyme is driven by the adsorption of the PEG chain. The results provide insight into the adsorption mechanisms of polymer-modified proteins on hydrophobic chromatographic resins.

Preparation and Characterization of Modified Soda Lignin with Polyethylene Glycol

PubMed Central

Zhang, Fangda; Lin, Jian; Zhao, Guangjie

2016-01-01

Soda lignin does not have thermal flowing characteristics and it is impossible for it to be further thermally molded. To achieve the fusibility of soda lignin for fiber preparation by melt-spinning, an effective method for soda lignin modification was conducted by cooking it with polyethylene glycol (PEG) 400 at various ratios. The higher the ratio of PEG that was used, the more PEG molecular chains were grafted at the alpha carbon of the soda lignin through ether bonds, resulting in lower thermal transition temperatures and more excellent fusibility. The modified soda lignin with a weight ratio of lignin to PEG of 1:4 exhibited a relative thermal stability of molten viscosity at selected temperatures. Thereafter, the resultant fusible soda lignin was successfully melt-spun into filaments with an average diameter of 33 ± 5 μm, which is smaller than that of some industrial lignins. Accordingly, it is possible to utilize soda lignin to produce fibrous carbonaceous materials. PMID:28773943

Evaluation of pH-sensitive poly(β-amino ester)-graft-poly(ethylene glycol) and its usefulness as a pH-sensor and protein carrier.

PubMed

Kim, Min Sang; Gao, Guang Hui; Kang, Seong Woo; Lee, Doo Sung

2011-07-07

In this study, some possible biomedical applications of a pH-sensitive and amphiphilic copolymer as a pH sensor and protein delivery system are reported. PAE-g-PEG was used as a pH-sensitive polymer that can exhibit a sharp pH-dependent transition. Various fluorescent dyes including pyrene and RITC can be used to label the pH-sensitive polymer PAE-g-PEG, which was evaluated for protein encapsulation. pH-sensing was possible by observing excimer formation of the labeled pyrene via pH-dependent expansion of the polymeric chain. Also, it was confirmed that FITC-BSA could be entrapped in RITC-labeled pH-sensitive micelles of PAE-g-PEG by FRET. As a result, PAE-g-PEG can be a pH sensor and carrier for protein delivery. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

New biodegradable dextran-based hydrogels for protein delivery: Synthesis and characterization.

PubMed

Pacelli, Settimio; Paolicelli, Patrizia; Casadei, Maria Antonietta

2015-08-01

A new derivative of dextran grafted with polyethylene glycol methacrylate through a carbonate bond (DEX-PEG-MA) has been synthesized and characterized. The photo-crosslinking reaction of DEX-PEG-MA allowed the obtainment of biodegradable networks tested for their mechanical and release properties. The new hydrogels were compared with those made of dextran methacrylate (DEX-MA), often employed as drug delivery systems of small molecules. The inclusion of PEG as a spacer created additional interactions among the polymeric chains improving the extreme fragility and lack of hardness typical of gels made of DEX-MA. Moreover, the different behavior in terms of swelling and degradability of the networks was able to affect the release of a model macromolecule over time, making DEX-PEG-MA matrices suitable candidates for the delivery of high molecular weight peptides. Interestingly, the combination of the two dextran derivatives showed intermediate ability to modulate the release of high molecular weight macromolecules. Copyright © 2015 Elsevier Ltd. All rights reserved.

A supramolecular miktoarm star polymer based on porphyrin metal complexation in water.

PubMed

Hou, Zhanyao; Dehaen, Wim; Lyskawa, Joël; Woisel, Patrice; Hoogenboom, Richard

2017-07-25

A novel supramolecular miktoarm star polymer was successfully constructed in water from a pyridine end-decorated polymer (Py-PmDEGA) and a metalloporphyrin based star polymer (ZnTPP-(PEG) 4 ) via metal-ligand coordination. The Py-PmDEGA moiety was prepared via a combination of reversible addition-fragmentation chain transfer polymerization (RAFT) and subsequent aminolysis and Michael addition reactions to introduce the pyridine end-group. The ZnTPP(PEG) 4 star-polymer was synthesized by the reaction between tetrakis(p-hydroxyphenyl)porphyrin and toluenesulfonyl-PEG, followed by insertion of a zinc ion into the porphyrin core. The formation of a well-defined supramolecular AB 4 -type miktoarm star polymer was unambiguously demonstrated via UV-Vis spectroscopic titration, isothermal titration calorimetry (ITC) and diffusion ordered NMR spectroscopy (DOSY).

Simulation of polyethylene glycol and calcium-mediated membrane fusion

NASA Astrophysics Data System (ADS)

Pannuzzo, Martina; De Jong, Djurre H.; Raudino, Antonio; Marrink, Siewert J.

2014-03-01

We report on the mechanism of membrane fusion mediated by polyethylene glycol (PEG) and Ca2+ by means of a coarse-grained molecular dynamics simulation approach. Our data provide a detailed view on the role of cations and polymer in modulating the interaction between negatively charged apposed membranes. The PEG chains cause a reduction of the inter-lamellar distance and cause an increase in concentration of divalent cations. When thermally driven fluctuations bring the membranes at close contact, a switch from cis to trans Ca2+-lipid complexes stabilizes a focal contact acting as a nucleation site for further expansion of the adhesion region. Flipping of lipid tails induces subsequent stalk formation. Together, our results provide a molecular explanation for the synergistic effect of Ca2+ and PEG on membrane fusion.

Release mechanisms of acetaminophen from polyethylene oxide/polyethylene glycol matrix tablets utilizing magnetic resonance imaging.

PubMed

Tajiri, Tomokazu; Morita, Shigeaki; Sakamoto, Ryosaku; Suzuki, Masazumi; Yamanashi, Shigeyuki; Ozaki, Yukihiro; Kitamura, Satoshi

2010-08-16

Release mechanism of acetaminophen (AAP) from extended-release tablets of hydrogel polymer matrices containing polyethylene oxide (PEO) and polyethylene glycol (PEG) were achieved using flow-through cell with magnetic resonance imaging (MRI). The hydrogel forming abilities are observed characteristically and the layer thickness which is corresponding to the diffusion length of AAP has a good correlation with the drug release profiles. In addition, polymeric erosion contribution to AAP releasing from hydrogel matrix tablets was directly quantified using size-exclusion chromatography (SEC). The matrix erosion profile indicates that the PEG erosion kinetic depends primarily on the composition ratio of PEG to PEO. The present study has confirmed that the combination of in situ MRI and SEC should be well suited to investigate the drug release mechanisms of hydrogel matrix such as PEO/PEG. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Study of PEG Tether Length of Pegylated-Lipid Sensing Films in QCM Odor Sensors

NASA Astrophysics Data System (ADS)

Wyszynski, Bartosz; Somboon, Pakpum; Nakamoto, Takamichi

Odor sensing system using quartz crystal microbalance (QCM) sensor array and pattern recognition technique has been for a long time an important research topic. Research of novel sensing materials for QCM odor sensors is vital for realization of artificial olfaction and related devices such as odor recorder. Herein we study quartz crystal microbalance (QCM, 20 MHz, AT-cut) sensors coated with lipopolymers with polyethylene glycol (PEG) as a tether. The tether's molecular weights were 1000, 2000 and 5000. In addition, we fabricated QCM sensors coated with PEGs of molecular weights 1000, 2000 and 4000. The fabricated sensors' properties were evaluated during experiments of exposures to vapors of alcohols, esters and acids. From the obtained results it is clear that the tether's length (molecular weight) is an important factor influencing the resulting material's sensing properties. Sensititivity patterns of the lipopolymeric sensors were clealrly different from the ones for respective polymers. The obtained sensors seem to have a good capability to discriminate among odor samples according to the functional group of an odorant.

Chlorine effect on the formation of carbon nanofibers.

PubMed

Lin, Wang-Hua; Takahashi, Yusuke; Li, Yuan-Yao; Sakoda, Akiyoshi

2012-12-01

Platelet graphite nanofibers (GNFs) and turbostratic carbon nanofibers (CNFs) are synthesized by the thermal evaporation and decomposition of a polymer-based mixture at 700 degrees C using Ni as a catalyst. The mixture consists of poly(ethylene glycol) (PEG), serving as the carbon source, and hydrochloric acid solution (HCl(aq)), serving as the promoter/additive for the growth of CNFs. High-purity zigzag-shaped platelet GNFs form with 10 wt% HCl(aq) as an additive in the PEG. The diameters of the platelet GNFs are in the range of 40-60 nm, with lengths of a few micrometers. High-resolution transmission electron microscopy images indicate a high degree of graphitization and well ordered graphene layers along the fiber axis. In contrast, high-purity turbostratic CNFs form with 20 wt% HCl(aq) in the PEG. The diameter and length of the turbostratic CNFs are 20-40 nm and a few micrometers, respectively. The participation of HCl in the thermal process leads to the formation of Ni-Cl compounds. The amount of chlorine affects the shape of the Ni catalyst, which determines the type of CNF formed.

Silk Fibroin Aqueous-Based Adhesives Inspired by Mussel Adhesive Proteins.

PubMed

Burke, Kelly A; Roberts, Dane C; Kaplan, David L

2016-01-11

Silk fibroin from the domesticated silkworm Bombyx mori is a naturally occurring biopolymer with charged hydrophilic terminal regions that end-cap a hydrophobic core consisting of repeating sequences of glycine, alanine, and serine residues. Taking inspiration from mussels that produce proteins rich in L-3,4-dihydroxyphenylalanine (DOPA) to adhere to a variety of organic and inorganic surfaces, the silk fibroin was functionalized with catechol groups. Silk fibroin was selected for its high molecular weight, tunable mechanical and degradation properties, aqueous processability, and wide availability. The synthesis of catechol-functionalized silk fibroin polymers containing varying amounts of hydrophilic polyethylene glycol (PEG, 5000 g/mol) side chains was carried out to balance silk hydrophobicity with PEG hydrophilicity. The efficiency of the catechol functionalization reaction did not vary with PEG conjugation over the range studied, although tuning the amount of PEG conjugated was essential for aqueous solubility. Adhesive bonding and cell compatibility of the resulting materials were investigated, where it was found that incorporating as little as 6 wt % PEG prior to catechol functionalization resulted in complete aqueous solubility of the catechol conjugates and increased adhesive strength compared with silk lacking catechol functionalization. Furthermore, PEG-silk fibroin conjugates maintained their ability to form β-sheet secondary structures, which can be exploited to reduce swelling. Human mesenchymal stem cells (hMSCs) proliferated on the silks, regardless of PEG and catechol conjugation. These materials represent a protein-based approach to catechol-based adhesives, which we envision may find applicability as biodegradable adhesives and sealants.

Influence of water-soluble channeling agents on the release of diclofenac sodium from Irvingia malayana wax matrix tablets.

PubMed

Yotsawimonwat, Songwut; Charumanee, Suporn; Kaewvichit, Sayam; Sirithunyalug, Jakkapan; Sirisa-Ard, Panee; Piyamongkol, Sirivipa; Siangwong, Kulthawat

2017-05-01

Irvingia malayana wax (IW) is majorly composed of esters of medium chain fatty acids. Its melting point is low and closed to the body temperature. This study aimed at investigating the potential of IW as a matrix-forming agent and evaluate the effect of soluble channeling agents on the release of diclofenac sodium (DS) from IW matrix tablets. The preformulation study by infrared spectroscopy and differential scanning calorimetry showed no incompatibility between IW and DS or soluble channeling agents, namely PEG 4000, PEG 6000 and lactose. IW retarded the release of DS from the matrix tablets more efficiently than carnauba wax due to its greater hydrophobicity and its ability to become partial molten wax at 37° C. Factors affecting the release of DS from IW matrix were drug concentrations, and types and concentrations of channeling agents. The release of DS significantly improved when DS concentration reached approximately 33%. The fast dissolving channeling agent, lactose, could enhance the drug release rate more effectively than PEG 4000 and PEG 6000, respectively. The linear relationship between the DS release rate and the concentration of the chosen channeling agent, PEG 6000, was found (r 2 =0.9866).

Zn(II)-PEG 300 globules as soft template for the synthesis of hexagonal ZnO micronuts by the hydrothermal reaction method.

PubMed

Shi, Xixi; Pan, Lingling; Chen, Shuoping; Xiao, Yong; Liu, Qiaoyun; Yuan, Liangjie; Sun, Jutang; Cai, Lintao

2009-05-19

Hexagonal ZnO micronuts (HZMNs) have been successfully synthesized with the assistance of poly(ethylene glycol) (PEG) 300 via a hydrothermal method. The structure and morphology of the HZMNs were characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and selected area electron diffraction (SAED). An individual ZnO micronut is revealed as twinned crystals. Time-dependent investigation shows that the growth of HZMNs involves a dissolution-recrystallization process followed by Ostwald ripening, in which is the first formed solid ZnO particles dissolve and transform to HZMNs with hollow structure. PEG 300 has been found to play a crucial role in the growth of this unique hollow structure. TEM observations show that the PEG chains aggregate to globules in water, which then have interaction with the dissolved zinc species to form the globules in a coiled state under hydrothermal conditions. These Zn(II)-PEG 300 globules act as soft template for the growth of HZMNs, and the possible growth mechanism is proposed. The room-temperature photoluminescence (PL) spectrum shows red emission around 612 nm with a full width at half-maximum (fwhm) only about 13 nm.

The influence of polymer molecular weight in lamellar gels based on PEG-lipids.

PubMed Central

Warriner, H E; Keller, S L; Idziak, S H; Slack, N L; Davidson, P; Zasadzinski, J A; Safinya, C R

1998-01-01

We report x-ray scattering, rheological, and freeze-fracture and polarizing microscopy studies of a liquid crystalline hydrogel called Lalpha,g. The hydrogel, found in DMPC, pentanol, water, and PEG-DMPE mixtures, differs from traditional hydrogels, which require high MW polymer, are disordered, and gel only at polymer concentrations exceeding an "overlap" concentration. In contrast, the Lalpha,g uses very low-molecular-weight polymer-lipids (1212, 2689, and 5817 g/mole), shows lamellar order, and requires a lower PEG-DMPE concentration to gel as water concentration increases. Significantly, the Lalpha,g contains fluid membranes, unlike Lbeta' gels, which gel via chain ordering. A recent model of gelation in Lalpha phases predicts that polymer-lipids both promote and stabilize defects; these defects, resisting shear in all directions, then produce elasticity. We compare our observations to this model, with particular attention to the dependence of gelation on the PEG MW used. We also use x-ray lineshape analysis of scattering from samples spanning the fluid-gel transition to obtain the elasticity coefficients kappa and B; this analysis demonstrates that although B in particular depends strongly on PEG-DMPE concentration, gelation is uncorrelated to changes in membrane elasticity. PMID:9649387

Unit and internal chain profiles of maca amylopectin.

PubMed

Zhang, Ling; Li, Guantian; Yao, Weirong; Zhu, Fan

2018-03-01

Unit chain length distributions of amylopectin and its φ, β-limit dextrins, which reflect amylopectin internal structure from three maca starches, were determined by high-performance anion-exchange chromatography with pulsed amperometric detection after debranching, and the samples were compared with maize starch. The amylopectins exhibited average chain lengths ranging from 16.72 to 17.16, with ranges of total internal chain length, external chain length, and internal chain length of the maca amylopectins at 12.49 to 13.68, 11.24 to 11.89, and 4.27 to 4.48. The average chain length, external chain length, internal chain length, and total internal chain length were comparable in three maca amylopectins. Amylopectins of the three maca genotypes studied here presented no significant differences in their unit chain length profiles, but did show significant differences in their internal chain profiles. Additional genetic variations between different maca genotypes need to be studied to provide unit- and internal chain profiles of maca amylopectin. Copyright © 2017. Published by Elsevier Ltd.

Alleviation of Osmotic Stress Effects by Exogenous Application of Salicylic or Abscisic Acid on Wheat Seedlings

PubMed Central

Marcińska, Izabela; Czyczyło-Mysza, Ilona; Skrzypek, Edyta; Grzesiak, Maciej T.; Janowiak, Franciszek; Filek, Maria; Dziurka, Michał; Dziurka, Kinga; Waligórski, Piotr; Juzoń, Katarzyna; Cyganek, Katarzyna; Grzesiak, Stanisław

2013-01-01

The aim of the study was to assess the role of salicylic acid (SA) and abscisic acid (ABA) in osmotic stress tolerance of wheat seedlings. This was accomplished by determining the impact of the acids applied exogenously on seedlings grown under osmotic stress in hydroponics. The investigation was unique in its comprehensiveness, examining changes under osmotic stress and other conditions, and testing a number of parameters simultaneously. In both drought susceptible (SQ1) and drought resistant (CS) wheat cultivars, significant physiological and biochemical changes were observed upon the addition of SA (0.05 mM) or ABA (0.1 μM) to solutions containing half-strength Hoagland medium and PEG 6000 (−0.75 MPa). The most noticeable result of supplementing SA or ABA to the medium (PEG + SA and PEG + ABA) was a decrease in the length of leaves and roots in both cultivars. While PEG treatment reduced gas exchange parameters, chlorophyll content in CS, and osmotic potential, and conversely, increased lipid peroxidation, soluble carbohydrates in SQ1, proline content in both cultivars and total antioxidants activity in SQ1, PEG + SA or PEG + ABA did not change the values of these parameters. Furthermore, PEG caused a two-fold increase of endogenous ABA content in SQ1 and a four-fold increase in CS. PEG + ABA increased endogenous ABA only in SQ1, whereas PEG + SA caused a greater increase of ABA content in both cultivars compared to PEG. In PEG-treated plants growing until the harvest, a greater decrease of yield components was observed in SQ1 than in CS. PEG + SA, and particularly PEG + ABA, caused a greater increase of these yield parameters in CS compared to SQ1. In conclusion, SA and ABA ameliorate, particularly in the tolerant wheat cultivar, the harmful effects and after effects of osmotic stress induced by PEG in hydroponics through better osmotic adjustment achieved by an increase in proline and carbohydrate content as well as by an increase in antioxidant activity. PMID:23803653

Electrically controlled microvalves to integrate microchip polymerase chain reaction and capillary electrophoresis.

PubMed

Kaigala, Govind V; Hoang, Viet N; Backhouse, Christopher J

2008-07-01

Microvalves are key in realizing portable miniaturized diagnostic platforms. We present a scalable microvalve that integrates well with standard lab on a chip (LOC) implementations, yet which requires essentially no external infrastructure for its operation. This electrically controlled, phase-change microvalve is used to integrate genetic amplification and analysis via capillary electrophoresis--the basis of many diagnostics. The microvalve is actuated using a polymer (polyethylene glycol, PEG) that exhibits a large volumetric change between its solid and liquid phases. Both the phase change of the PEG and the genetic amplification via polymerase chain reaction (PCR) are thermally controlled using thin film resistive elements that are patterned using standard microfabrication methods. By contrast with many other valve technologies, these microvalves and their control interface scale down in size readily. The novelty here lies in the use of fully integrated microvalves that require only electrical connections to realize a portable and inexpensive genetic analysis platform.

Surgical Outcomes of Plaque Excision and Grafting and Supplemental Tunica Albuginea Plication for Treatment of Peyronie's Disease With Severe Compound Curvature.

PubMed

Chow, Alexander K; Sidelsky, Steven A; Levine, Laurence A

2018-05-22

There are limited data in the literature that describe the management of Peyronie's disease (PD) with severe compound curvature, which often requires additional straightening procedures after plaque excision and grafting (PEG) to achieve functional penile straightening (<20 degrees). This study highlights the clinical distinction and our experience with men with PD and severe compound curvature treated with PEG and supplemental tunica albuginea plication (TAP). We performed a retrospective chart review of patients with PD and acute angulation who underwent PEG (group 1) and patients with compound curvature who underwent PEG with TAP (group 2) between 2007 and 2016. Primary post-operative outcomes of interest include change in penile curvature, change in measured stretched penile length, and subjective report on penile sensation and sexually induced penile rigidity. 240 Men with PD were included in the study, of which 79 (33%) patients in group 1 underwent PEG and 161 (67%) in group 2 underwent PEG and TAP. There was no difference in associated PD co-morbidities including age, hypertension, hyperlipidemia, hypogonadism, diabetes, or tobacco use. After artificial induction of erection with intracorporal trimix injection, the average primary curvature was 73 (range, 20-120) degrees for group 1 compared to 79 (range, 35-140) degrees for group 2 (P = .01). Group 2 had an average secondary curvature of 36 (20-80 degrees). After completion of PEG, men in group 2 had an average residual curvature of 30 (range, 20-50) degrees which required 1-6 TAPs to achieve functional straightness (<20 degrees). At an average follow-up of 61 months, there was no difference for group 1 and group 2, respectively, for recurrent curvature (11.4% vs 12.4%, P = .33), change in penile length (+0.57 vs +0.36 cm, P = .27) or decreased penile sensation (6% vs 13%, P = .12). In all, 81% of group 1 and 79% of group 2 were able to engage in penetrative sex after penile straightening with or without pharmacotherapy (P = .73). Our review shows promising surgical outcomes for the use of PEG and supplemental TAP for this subtype of complex PD. This article reports the largest experience with treatment of PD with compound curvature to date. Limitations of this study include the retrospective nature of the analysis as well as the lack of a validated objective measurement of erectile function after penile straightening. Our study found no baseline difference in underlying co-morbidities in men with severe compound curvature compared with men with acute severe angulated curvature. Men with severe compound curvature represent a severe and under-recognized population of men with PD who can be surgically corrected with PEG and supplemental TAP(s) when needed without an increased risk of loss of penile length, recurrent curvature, decreased penile sensation, or erectile dysfunction when compared to men treated with PEG alone. Chow AK, Sidelsky SA, Levine LA. Surgical Outcomes of Plaque Excision and Grafting and Supplemental Tunica Albuginea Plication for Treatment of Peyronie's Disease With Severe Compound Curvature. J Sex Med 2018;XX:XXX-XXX. Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Study of nanoscale structures in hydrated biomaterials using small-angle neutron scattering

PubMed Central

Luk, Arnold; Murthy, N. Sanjeeva; Wang, Wenjie; Rojas, Ramiro; Kohn, Joachim

2012-01-01

Distribution of water in three classes of biomedically relevant and degradable polymers was investigated using small-angle neutron scattering. In semicrystalline polymers, such as poly(lactic acid) and poly(glycolic acid), water was found to diffuse preferentially into the noncrystalline regions. In amorphous polymers, such as poly(D,L-lactic acid) and poly(lactic-co-glycolic acid), the scattering after 7-days of incubation was attributed to water in microvoids that form following the hydrolytic degradation of the polymer. In amorphous copolymers containing hydrophobic segments (desaminotyrosyl-tyrosine ethyl ester) and hydrophilic blocks (poly(ethylene glycol) PEG), a sequence of distinct regimes of hydration were observed: homogeneous distribution (~ 10 Å length scales) at <13 wt% PEG (~ 1 water per EG), clusters of hydrated domains (~50 Å radius) separated at 24 wt% PEG (1 to 2 water per EG), uniformly distributed hydrated domains at 41 wt% PEG (~ 4 water per EG), and phase inversion at > 50 wt% PEG ( > 6 water per EG ). Increasing PEG content increased the number of these domains with only a small decrease in distance between the domains. These discrete domains appeared to coalesce to form submicron droplets at ~60 °C, above the melting temperature of crystalline PEG. Significance of such observations on the evolution of μm size channels that form during hydrolytic erosion is discussed. PMID:22227373

Dynamics of gold nanoparticles in synthetic and biopolymer solutions

NASA Astrophysics Data System (ADS)

Kohli, Indermeet

Soft matter systems of colloidal particles, polymers, amphiphiles and liquid crystals are ubiquitous in our everyday life. Food, plastics, soap and even human body is comprised of soft materials. Research conducted to understand the behavior of these soft matter systems at molecular level is essential for many interdisciplinary fields of study as well as important for many technological applications. We used gold nanoparticles (Au NPs) to investigate the length-scale dependent dynamics in semidilute poly(ethylene glycol) (PEG)-water, bovine serum albumin (BSA)-phosphate buffer, dextran and particulate solutions. In case of PEG-water solutions, fluctuation correlation spectroscopy was used to measure the diffusion coefficients (D) of the NPs as a function of their radius, Ro (2.5-10 nm), PEG volume fraction, φ (0-0.37) and molecular weight, Mw (5 kg/mol and 35 kg/mol). Our results indicate that the radius of gyration, Rg of the polymer chain is the crossover length scale for the NPs experiencing nanoviscosity or macroviscosity. In BSA-phosphate buffer solutions, we observed a monolayer formation at the NP surface with a thickness of 3.8 nm. The thickness of the adsorbed layer was independent of NP size. Best fit was obtained by the anticooperative binding model with the Hill coefficient of n = 0.63. Dissociation constant (KD) increased with particle size indicating stronger interaction of BSA with smaller sized NPs. We also contrasted the diffusion of gold nanoparticles (AuNPs) in crowded solutions of randomly branched polymer (dextran) and rigid, spherical particles (silica) to understand the roles played by the probe size and structure of the crowding agent in determining the probe diffusion. AuNPs of two different sizes (2.5 nm & 10 nm), dextran of molecular weight 70 kDa and silica particles of radius 10 nm were used. Our results indicated that the AuNP diffusion can be described using the bulk viscosity of the matrix and hydrodynamically dextran behaved similar to soft colloid. In all situations, we observed normal diffusion except for 2.5 nm sized AuNP particles in dextran solution at higher volume fraction. This was caused by transient trapping of particles within the random branches. The results showed the importance of macromolecular architecture in determining the transport properties in intracellular matrix and in cells with spiny dendrites.

An Electrochemical DNA Biosensor for the Detection of Salmonella Using Polymeric Films and Electrochemical Labels

NASA Astrophysics Data System (ADS)

Diaz Serrano, Madeline

Waterborne and foodborne diseases are one of the principal public health problems worldwide. Microorganisms are the major agents of foodborne illness: pathogens such as Salmonella, Campylobacter jejuni and Escherichia coli, and parasites such as cryptosporidium. The most popular methods to detect Salmonella are based on culture and colony counting methods, ELISA, Gel electrophoresis and the polymerase chain reaction. Conventional detection methods are laborious and time-consuming, allowing for portions of the food to be distributed, marketed, sold and eaten before the analysis is done and the problem even detected. By these reasons, the rapid, easy and portable detection of foodborne organisms will facilitate the disease treatment. Our particular interest is to develop a nucleic acid biosensor (NAB) for the detection of pathogenic microorganisms in food and water samples. In this research, we report on the development of a NAB prototype using a polymer modified electrode surface together with sequences of different lengths for the OmpC gene from Salmonella as probes and Ferrocene-labeled target (Fc-ssDNA), Ferrocene-labeled tri(ethylene glycol) (Fc-PEG) and Ruthenium-Ferrocene (Ru-Fe) bimetallic complex as an electrochemical labels. We have optimized several PS films and anchored nucleic acid sequences with different lengths at gold and carbon surfaces. Non contact mode AFM and XPS were used to monitor each step of the NAB preparation, from polymer modification to oligos hybridization (conventional design). The hybridization reaction was followed electrochemically using a Fc-ssDNA and Fc-PEG in solution taking advantage of the morphological changes generated upon hybridization. We observed a small current at the potential for the Fe oxidation without signal amplification at +296 mV vs. Ag/AgCl for the Fc-ssDNA strategy and a small current at +524 mV for the Fc-PEG strategy. The immobilization, hybridization and signal amplification of Biotin- OmpC Salmonella genes generated by E.Z. Vega were obtained on NHS-PS-NHS 10.3 KD and detected by SWV and CC using Ru-Fe bimetallic complex as a redox label and GOx/glucose in PBS buffer. Calibration curves of biotin-OmpC probe hybridization were performed by CC, a catalytic charge was observed due to the presence of Ru-Fe bimetallic complex, GOx-A and glucose. The lowest target sequence detectable concentration was 0.41 microM.

The in vitro kinetics of the interactions between PEG-ylated magnetic-fluid-loaded liposomes and macrophages.

PubMed

Martina, Marie-Sophie; Nicolas, Valerie; Wilhelm, Claire; Ménager, Christine; Barratt, Gillian; Lesieur, Sylviane

2007-10-01

Binding and uptake kinetics of magnetic-fluid-loaded liposomes (MFL) by endocytotic cells were investigated in vitro on the model cell-line J774. MFL consisted of unilamellar phosphatidylcholine vesicles (mean hydrodynamic diameter close to 200nm) encapsulating 8-nm nanocrystals of maghemite (gamma-Fe(2)O(3)) and sterically stabilized by introducing 5mol% of distearylphosphatidylcholine poly(ethylene glycol)(2,000) (DSPE-PEG(2,000)) in the vesicle bilayer. The association processes with living macrophages were followed at two levels. On one hand, the lipid vesicles were imaged by confocal fluorescence microscopy. For this purpose 1mol% of rhodamine-marked phosphatidylethanolamine was added to the liposome composition. On the other hand, the iron oxide particles associated with cells were independently quantified by magnetophoresis. All the experiments were similarly performed with PEG-ylated or conventional MFL to point out the role of polymer coating. The results showed cell association with both types of liposomes resulting from binding followed by endocytosis. Steric stabilization by PEG chains reduced binding efficiency limiting the amount of MFL internalized by the macrophages. In contrast, PEG coating did not change the kinetics of endocytosis which exhibited the same first-order rate constant for both conventional and PEG-ylated liposomes. Moreover, lipids and iron oxide particle uptakes were perfectly correlated, indicating that MFL vesicle structure and encapsulation rate were preserved upon cell penetration.

Effects of temperature and PEG grafting density on the translocation of PEGylated nanoparticles across asymmetric lipid membrane.

PubMed

Zhang, Zuoheng; Lin, Xubo; Gu, Ning

2017-12-01

Plasma membrane internalization of nanoparticles (NPs) is important for their biomedical applications such as drug-delivery carriers. On one hand, in order to improve their half-life in circulation, PEGylation has been widely used. However, it may hinder the NPs' membrane internalization ability. On the other hand, higher temperature could enhance the membrane permeability and may affect the NPs' ability to enter into or exit from cells. To make full use of their advantages, we systematically investigated the effects of temperature and PEG density on the translocation of PEGylated nanoparticles across the plasma asymmetric membrane of eukaryotic cells, using near-atom level coarse-grained molecular dynamics simulations. Our results showed that higher temperature could accelerate the translocation of NPs across membranes by making lipids more disorder and faster diffusion. On the contrary, steric hindrance effects of PEG would inhibit NPs' translocation process and promote lipids flip-flops. The PEG chains could rearrange themselves to minimize the contacts between PEG and lipid tails during the translocation, which was similar to 'snorkeling effect'. Moreover, lipid flip-flops were affected by PEGylated density as well as NPs' translocation direction. Higher PEG grafting density could promote lipid flip-flops, but inhibit lipid extraction from bilayers. The consequence of lipid flip-flop and extraction was that the membranes got more symmetric. Copyright © 2017. Published by Elsevier B.V.

Effects of cold plasma treatment on alfalfa seed growth under simulated drought stress

NASA Astrophysics Data System (ADS)

Jinkui, FENG; Decheng, WANG; Changyong, SHAO; Lili, ZHANG; Xin, TANG

2018-03-01

The effect of different cold plasma treatments on the germination and seedling growth of alfalfa (Medicago sativa L.) seeds under simulated drought stress conditions was investigated. Polyethyleneglycol-6000 (PEG 6000)with the mass fraction of 0% (purified water), 5%, 10%, and 15% were applied to simulate the drought environment. The alfalfa seeds were treated with 15 different power levels ranged between 0-280 W for 15 s. The germination potential, germination rate, germination index, seedling root length, seedling height, and vigor index were investigated. Results indicated significant differences between treated with proper power and untreated alfalfa seeds. With the increase of treatment power, these indexes mentioned above almost presented bimodal curves. Under the different mass fractions of PEG 6000, results showed that the lower power led to increased germination, and the seedlings presented good adaptability to different drought conditions. Meanwhile, higher power levels resulted in a decreased germination rate. Seeds treated with 40 W resulted in higher germination potential, germination rate, seedling height, root length, and vigor index. Vigor indexes of the treated seeds under different PEG 6000 stresses increased by 38.68%, 43.91%, 74.34%, and 39.20% respectively compared to CK0-0, CK5-0, CK10-0, and CK15-0 (the control sample under 0%, 5%, 10%, and 15% PEG 6000). Therefore, 40 W was regarded as the best treatment in this research. Although the trend indexes of alfalfa seeds treated with the same power were statistically the same under different PEG 6000 stresses, the cold plasma treatment had a significant effect on the adaptability of alfalfa seeds in different drought environments. Thus, this kind of treatment is worth implementing to promote seed growth under drought situations.

Interaction of proteins with weak amphoteric charged membrane surfaces: effect of pH.

PubMed

Matsumoto, Hidetoshi; Koyama, Yoshiyuki; Tanioka, Akihiko

2003-08-01

Weak amphoteric charged membranes were prepared by the graft copolymerization of poly(ethylene glycol) (PEG) derivatives with pendant ionizable groups onto polyethylene (PE) porous membranes. Two types of weak amphoteric charged membranes and two types of weak single charged membranes were prepared. The pH dependence of the protein (fluorescein isothiocyanate-labeled bovine serum albumin, FITC-BSA) adsorption onto the membranes was investigated by fluorescence spectroscopy. The interfacial charge properties of the membranes and protein were also characterized at different pH values by streaming potential and electrophoretic light scattering (ELS) measurements, respectively. The adsorbed amount onto each ionic PEG chain grafted membrane showed a uniform maximum value near the isoelectric point (IEP) of the protein (pH 4.1). On both sides of the IEP (pHs 3.3 and 7.2), the adsorption experiments and zeta (zeta) potential measurements were well correlated: the contribution of electrostatic interaction was dominant for the protein adsorption behavior. In the alkaline condition (pH 10.2), the adsorption experiments contradict the zeta potential measurements. It suggested that the conformational change of protein molecule influenced the adsorption behavior. Finally, these results indicated the potential of controlling the protein-ionic PEG chain interaction on the membrane surfaces by the pH adjustment of the outer solution.

Period of an Interrupted Pendulum

NASA Astrophysics Data System (ADS)

Miller, Bradley E.

2002-11-01

While demonstrating a classic conservation-of-energy problem to my AP Physics students, I became curious about the periodic motion that ensued for certain initial conditions. The original problem consists of releasing a mass at the end of a string from an initial position horizontal to the plane of a table. The string comes in contact with a peg some distance below the point where the string is attached at the top. One is asked to find what minimum fraction of the string's length should the peg be placed to have the mass complete a circle about the peg. However, when the mass is released from much lower heights, the system undergoes periodic motion that can be thought of as an interrupted pendulum.

The traveling salesman problem in surgery: economy of motion for the FLS Peg Transfer task.

PubMed

Falcone, John L; Chen, Xiaotian; Hamad, Giselle G

2013-05-01

In the Peg Transfer task in the Fundamentals of Laparoscopic Surgery (FLS) curriculum, six peg objects are sequentially transferred in a bimanual fashion using laparoscopic instruments across a pegboard and back. There are over 268 trillion ways of completing this task. In the setting of many possibilities, the traveling salesman problem is one where the objective is to solve for the shortest distance traveled through a fixed number of points. The goal of this study is to apply the traveling salesman problem to find the shortest two-dimensional path length for this task. A database platform was used with permutation application output to generate all of the single-direction solutions of the FLS Peg Transfer task. A brute-force search was performed using nested Boolean operators and database equations to calculate the overall two-dimensional distances for the efficient and inefficient solutions. The solutions were found by evaluating peg object transfer distances and distances between transfers for the nondominant and dominant hands. For the 518,400 unique single-direction permutations, the mean total two-dimensional peg object travel distance was 33.3 ± 1.4 cm. The range in distances was from 30.3 to 36.5 cm. There were 1,440 (0.28 %) of 518,400 efficient solutions with the minimized peg object travel distance of 30.3 cm. There were 8 (0.0015 %) of 518,400 solutions in the final solution set that minimized the distance of peg object transfer and minimized the distance traveled between peg transfers. Peg objects moved 12.7 cm (17.4 %) less in the efficient solutions compared to the inefficient solutions. The traveling salesman problem can be applied to find efficient solutions for surgical tasks. The eight solutions to the FLS Peg Transfer task are important for any examinee taking the FLS curriculum and for certification by the American Board of Surgery.

Enhancement in Elastic Bending Rigidity of Polymer Loaded Reverse Microemulsions.

PubMed

Geethu, P M; Yadav, Indresh; Aswal, Vinod K; Satapathy, Dillip K

2017-11-14

Elastic bending rigidity of the surfactant shell is a crucial parameter which determines the phase behavior and stability of microemulsion droplets. For water-in-oil reverse microemulsions stabilized by AOT (sodium 1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate) surfactant, the elastic bending rigidity is close to thermal energy at room temperature (k B T) and can be modified by the presence of hydrophilic polymers. Here, we explore the influence of two polymers polyethylene glycol (PEG) and polyvinylpyrrolidone (PVP), both having nearly same size (radius of gyration, R g ) but different dipole moment, on elastic bending rigidity of water-AOT-n-decane reverse microemulsions via estimating the percolation temperatures (T P ) and droplet radii using dielectric relaxation spectroscopy (DRS) and small-angle neutron scattering (SANS) techniques. Notably, an increase in T P is observed on introducing PEG and PVP polymers and is attributed to the adsorption of polymer chains onto the surfactant monolayer. The stability of the droplet phase of microemulsion after the incorporation of PEG and PVP polymers is confirmed by contrast matching SANS experiments. An enhancement in elastic bending rigidity of AOT surfactant shell amounting to ∼46% is observed upon incorporation of PVP into the droplet core, whereas for PEG addition, a smaller increase of about 17% is recorded. We conjecture that the considerable increase in elastic bending rigidity of the surfactant monolayer upon introducing PVP is because of the strong ion-dipole interaction between anionic AOT and dipoles present along the PVP polymer chains. Scaling exponents extracted from the temperature dependent electrical conductivity measurements and the frequency dependent scaling of conductivity at percolation indicate the dynamic nature of percolation for both pure and polymer loaded reverse microemulsions. The decrease in activation energy of percolation upon incorporating PEG and PVP polymer molecules also reflects the increased stability of microemulsion droplets against thermal fluctuations.

Polymer sol-gel composite inverse opal structures.

PubMed

Zhang, Xiaoran; Blanchard, G J

2015-03-25

We report on the formation of composite inverse opal structures where the matrix used to form the inverse opal contains both silica, formed using sol-gel chemistry, and poly(ethylene glycol), PEG. We find that the morphology of the inverse opal structure depends on both the amount of PEG incorporated into the matrix and its molecular weight. The extent of organization in the inverse opal structure, which is characterized by scanning electron microscopy and optical reflectance data, is mediated by the chemical bonding interactions between the silica and PEG constituents in the hybrid matrix. Both polymer chain terminus Si-O-C bonding and hydrogen bonding between the polymer backbone oxygens and silanol functionalities can contribute, with the polymer mediating the extent to which Si-O-Si bonds can form within the silica regions of the matrix due to hydrogen-bonding interactions.

Amphiphilic, cross-linkable diblock copolymers for multifunctionalized nanoparticles as biological probes

NASA Astrophysics Data System (ADS)

Schmidtke, Christian; Pöselt, Elmar; Ostermann, Johannes; Pietsch, Andrea; Kloust, Hauke; Tran, Huong; Schotten, Theo; Bastús, Neus G.; Eggers, Robin; Weller, Horst

2013-07-01

Nanoparticles (NPs) play an increasingly important role in biological labeling and imaging applications. However, preserving their useful properties in an aqueous biological environment remains challenging, even more as NPs therein have to be long-time stable, biocompatible and nontoxic. For in vivo applications, size control is crucial in order to route excretion pathways, e.g. renal clearance vs. hepato-biliary accumulation. Equally necessary, cellular and tissue specific targeting demands suitable linker chemistry for surface functionalization with affinity molecules, like peptides, proteins, carbohydrates and nucleotides. Herein, we report a three stage encapsulation process for NPs comprised of (1) a partial ligand exchange by a multidentate polyolefinic amine ligand, PI-N3, (2) micellar encapsulation with a precisely tuned amphiphilic diblock PI-b-PEG copolymer, in which the PI chains intercalate to the PI-N3 prepolymer and (3) radical cross-linking of the adjacent alkenyl bonds. As a result, water-soluble NPs were obtained, which virtually maintained their primal physical properties and were exceptionally stable in biological media. PEG-terminal functionalization of the diblock PI-b-PEG copolymer with numerous functional groups was mostly straightforward by chain termination of the living anionic polymerization (LAP) with the respective reagents. More complex affinity ligands, e.g. carbohydrates or biotin, were introduced in a two-step process, prior to micellar encapsulation. Advantageously, this pre-assembly approach opens up rapid access to precisely tuned multifunctional NPs, just by using mixtures of diverse functional PI-b-PEG polymers in a combinatorial manner. All constructs showed no toxicity from 0.001 to 1 μM (particle concentration) in standard WST and LDH assays on A549 cells, as well as only marginal unspecific cellular uptake, even in serum-free medium.Nanoparticles (NPs) play an increasingly important role in biological labeling and imaging applications. However, preserving their useful properties in an aqueous biological environment remains challenging, even more as NPs therein have to be long-time stable, biocompatible and nontoxic. For in vivo applications, size control is crucial in order to route excretion pathways, e.g. renal clearance vs. hepato-biliary accumulation. Equally necessary, cellular and tissue specific targeting demands suitable linker chemistry for surface functionalization with affinity molecules, like peptides, proteins, carbohydrates and nucleotides. Herein, we report a three stage encapsulation process for NPs comprised of (1) a partial ligand exchange by a multidentate polyolefinic amine ligand, PI-N3, (2) micellar encapsulation with a precisely tuned amphiphilic diblock PI-b-PEG copolymer, in which the PI chains intercalate to the PI-N3 prepolymer and (3) radical cross-linking of the adjacent alkenyl bonds. As a result, water-soluble NPs were obtained, which virtually maintained their primal physical properties and were exceptionally stable in biological media. PEG-terminal functionalization of the diblock PI-b-PEG copolymer with numerous functional groups was mostly straightforward by chain termination of the living anionic polymerization (LAP) with the respective reagents. More complex affinity ligands, e.g. carbohydrates or biotin, were introduced in a two-step process, prior to micellar encapsulation. Advantageously, this pre-assembly approach opens up rapid access to precisely tuned multifunctional NPs, just by using mixtures of diverse functional PI-b-PEG polymers in a combinatorial manner. All constructs showed no toxicity from 0.001 to 1 μM (particle concentration) in standard WST and LDH assays on A549 cells, as well as only marginal unspecific cellular uptake, even in serum-free medium. Electronic supplementary information (ESI) available: Images of the QDs, toxicity data and NMR spectra. See DOI: 10.1039/c3nr01520c

The Modification of siRNA with 3′ Cholesterol to Increase Nuclease Protection and Suppression of Native mRNA by Select siRNA Polyplexes

PubMed Central

Ambardekar, Vishakha V.; Han, Huai-Yun; Varney, Michelle L.; Vinogradov, Serguei V.; Singh, Rakesh K.; Vetro, Joseph A.

2010-01-01

Polymer-siRNA complexes (siRNA polyplexes) are being actively developed to improve the therapeutic application of siRNA. A major limitation for many siRNA polyplexes, however, is insufficient mRNA suppression. Given that modifying the sense strand of siRNA with 3′ cholesterol (chol-siRNA) increases the activity of free nuclease-resistant siRNA in vitro and in vivo, we hypothesized that complexation of chol-siRNA can increase mRNA suppression by siRNA polyplexes. In this study, the characteristics and siRNA activity of self assembled polyplexes formed with chol-siRNA or unmodified siRNA were compared using three types of conventional, positively charged polymers: (i) biodegradable, cross-linked nanogels (BDNG) (ii) graft copolymers (PEI-PEG), and (iii) linear block copolymers (PLL10-PEG, and PLL50-PEG). Chol-siRNA did not alter complex formation or the resistance of polyplexes to siRNA displacement by heparin but increased nuclease protection by BDNG, PLL10-PEG, and PLL50-PEG polyplexes over polyplexes with unmodified siRNA. Chol-CYPB siRNA increased suppression of native CYPB mRNA in mammary microvascular endothelial cells (MVEC) by BDNG polyplexes (35%) and PLL10-PEG polyplexes (69%) over comparable CYPB siRNA polyplexes but had no effect on PEI-PEG or PLL50-PEG polyplexes. Overall, these results indicate that complexation of chol-siRNA increases nuclease protection and mRNA suppression by select siRNA polyplexes. These results also suggest that polycationic block length is an important factor in increasing mRNA suppression by PLL-PEG chol-siRNA polyplexes in mammary MVEC. PMID:21047680

The modification of siRNA with 3' cholesterol to increase nuclease protection and suppression of native mRNA by select siRNA polyplexes.

PubMed

Ambardekar, Vishakha V; Han, Huai-Yun; Varney, Michelle L; Vinogradov, Serguei V; Singh, Rakesh K; Vetro, Joseph A

2011-02-01

Polymer-siRNA complexes (siRNA polyplexes) are being actively developed to improve the therapeutic application of siRNA. A major limitation for many siRNA polyplexes, however, is insufficient mRNA suppression. Given that modifying the sense strand of siRNA with 3' cholesterol (chol-siRNA) increases the activity of free nuclease-resistant siRNA in vitro and in vivo, we hypothesized that complexation of chol-siRNA can increase mRNA suppression by siRNA polyplexes. In this study, the characteristics and siRNA activity of self assembled polyplexes formed with chol-siRNA or unmodified siRNA were compared using three types of conventional, positively charged polymers: (i) biodegradable, cross-linked nanogels (BDNG) (ii) graft copolymers (PEI-PEG), and (iii) linear block copolymers (PLL10-PEG, and PLL50-PEG). Chol-siRNA did not alter complex formation or the resistance of polyplexes to siRNA displacement by heparin but increased nuclease protection by BDNG, PLL10-PEG, and PLL50-PEG polyplexes over polyplexes with unmodified siRNA. Chol-CYPB siRNA increased suppression of native CYPB mRNA in mammary microvascular endothelial cells (MVEC) by BDNG polyplexes (35%) and PLL10-PEG polyplexes (69%) over comparable CYPB siRNA polyplexes but had no effect on PEI-PEG or PLL50-PEG polyplexes. Overall, these results indicate that complexation of chol-siRNA increases nuclease protection and mRNA suppression by select siRNA polyplexes. These results also suggest that polycationic block length is an important factor in increasing mRNA suppression by PLL-PEG chol-siRNA polyplexes in mammary MVEC. Copyright © 2010 Elsevier Ltd. All rights reserved.

pH-responsive supramolecular self-assembly of well-defined zwitterionic ABC miktoarm star terpolymers.

PubMed

Liu, Hao; Li, Changhua; Liu, Hewen; Liu, Shiyong

2009-04-21

We report the first example of the synthesis and pH-responsive supramolecular self-assembly of double hydrophilic ABC miktoarm star terpolymers. Well-defined ABC miktoarm star terpolymers consisting of poly(ethylene glycol), poly(tert-butyl methacrylate), and poly(2-(diethylamino)ethyl methacrylate) arms [PEG(-b-PtBMA)-b-PDEA] were synthesized via the combination of consecutive click reactions and atom transfer radical polymerization (ATRP), starting from a trifunctional core molecule, 1-azido-3-chloro-2-propanol (ACP). The click reaction of monoalkynyl-terminated PEG with an excess of ACP afforded difunctional PEG bearing a chlorine and a secondary hydroxyl moiety at the chain end, PEG113(-Cl)-OH (1). After azidation with NaN3, PEG-based macroinitiator PEG113(-N3)-Br (3) was prepared by the esterification of PEG113(-N3)-OH (2) with 2-bromoisobutyryl bromide and then employed in the ATRP of tert-butyl methacrylate (tBMA). The obtained PEG(-N3)-b-PtBMA copolymers (4) possessed an azido moiety at the diblock junction point. The preparation of PEG(-b-PtBMA)-b-PDEA miktoarm star terpolymers was then achieved via the click reaction of 4 with an excess of monoalkynyl-terminated PDEA. The obtained miktoarm star terpolymers were successfully converted into PEG(-b-PMAA)-b-PDEA, where PMAA is poly(methacrylic acid). In aqueous solution, PEG(-b-PMAA)-b-PDEA zwitterionic ABC miktoarm star terpolymers can self-assemble into three types of micellar aggregates by simply adjusting solution pH at room temperature. Above pH 8, PDEA-core micelles stabilized by PEG/ionized PMAA hybrid coronas were formed due to the insolubility of PDEA block. In the range of pH 5-7, micelles possessing polyion complex cores formed as a result of charge compensation between partially ionized PMAA and partially protonated PDEA sequences. At pH<4, hydrogen bonding interactions between fully protonated PMAA and PEG led to the formation of another type of micellar aggregates possessing hydrogen-bonded complex cores stabilized by protonated PDEA coronas. The fully reversible pH-responsive formation of three types of aggregates were characterized by 1H NMR, dynamic and static laser light scattering (LLS), and transmission electron microscopy (TEM).

Influence of polymer architecture on antigens camouflage, CD47 protection and complement mediated lysis of surface grafted red blood cells.

PubMed

Chapanian, Rafi; Constantinescu, Iren; Rossi, Nicholas A A; Medvedev, Nadia; Brooks, Donald E; Scott, Mark D; Kizhakkedathu, Jayachandran N

2012-11-01

Hyperbranched polyglycerol (HPG) and polyethylene glycol (PEG) polymers with similar hydrodynamic sizes in solution were grafted to red blood cells (RBCs) to investigate the impact of polymer architecture on the cell structure and function. The hydrodynamic sizes of polymers were calculated from the diffusion coefficients measured by pulsed field gradient NMR. The hydration of the HPG and PEG was determined by differential scanning calorimetry analyses. RBCs grafted with linear PEG had different properties compared to the compact HPG grafted RBCs. HPG grafted RBCs showed much higher electrophoretic mobility values than PEG grafted RBCs at similar grafting concentrations and hydrodynamic sizes indicating differences in the structure of the polymer exclusion layer on the cell surface. PEG grafting impacted the deformation properties of the membrane to a greater degree than HPG. The complement mediated lysis of the grafted RBCs was dependent on the type of polymer, grafting concentration and molecular size of grafted chains. At higher molecular weights and graft concentrations both HPG and PEG triggered complement activation. The magnitude of activation was higher with HPG possibly due to the presence of many hydroxyl groups per molecule. HPG grafted RBCs showed significantly higher levels of CD47 self-protein accessibility than PEG grafted RBCs at all grafting concentrations and molecular sizes. PEG grafted polymers provided, in general, a better shielding and protection to ABO and minor antigens from antibody recognition than HPG polymers, however, the compact HPGs provided greater protection of certain antigens on the RBC surface. Our data showed that HPG 20 kDa and HPG 60 kDa grafted RBCs exhibited properties that are more comparable to the native RBC than PEG 5 kDa and PEG 10 kDa grafted RBCs of comparable hydrodynamic sizes. The study shows that small compact polymers such as HPG 20 kDa have a greater potential in the generation of functional RBC for therapeutic delivery applications. The intermediate sized polymers (PEG or HPG) which showed greater antigen camouflage at lower grafting concentrations have significant potential in transfusion as universal red blood donor cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

Influence of the state of phase of lipid bilayer on the exposure of glucose residues on the surface of liposomes.

PubMed

Villalva, Denise Gradella; Giansanti, Luisa; Mauceri, Alessandro; Ceccacci, Francesca; Mancini, Giovanna

2017-11-01

The presence of carbohydrate-binding proteins (i.e. lectins) on the surface of various bacterial strains and their overexpression in some tumor tissues makes the use of glycosylated liposomes a promising approach for the specific drug delivery in antibacterial and anti-cancer therapies. However, the functionalization of liposome surface with sugar moieties by glycosylated amphiphiles does not ensure the binding of sugar-coated vesicles with lectins. In fact, the composition and properties of lipid bilayer play a pivotal role in the exposure of sugar residues and in the interaction with lectins. The influence of the length of the hydrophilic spacer that links the sugar to liposome surface and of the presence of saturated or unsaturated phospholipids in the lipid bilayer on the ability of glucosylated liposomes to interact with a model lectin, Concanavalin A, was investigated. Our results demonstrate that both the chain length and the prensece of unsaturation, parameters that strongly affect the fluidity of the lipid bilayer, affect agglutination. In particular, agglutination is favored when liposomes are in the gel phase within a defined range of temperature. Moreover, the obtained results confirm that the length of the PEG spacer, that influences both lipid organization and the exposure of sugar moieties to the bulk, plays a crucial role in liposome/lectin interaction. Copyright © 2017 Elsevier B.V. All rights reserved.

Antigenic peptides containing large PEG loops designed to extend out of the HLA-A2 binding site form stable complexes with class I major histocompatibility complex molecules.

PubMed Central

Bouvier, M; Wiley, D C

1996-01-01

Recognition of peptides bound to class I major histocompatibility complex (MHC) molecules by specific receptors on T cells regulates the development and activity of the cellular immune system. We have designed and synthesized de novo cyclic peptides that incorporate PEG in the ring structure for binding to class I MHC molecules. The large PEG loops are positioned to extend out of the peptide binding site, thus creating steric effects aimed at preventing the recognition of class I MHC complexes by T-cell receptors. Peptides were synthesized and cyclized on polymer support using high molecular weight symmetrical PEG dicarboxylic acids to link the side chains of lysine residues substituted at positions 4 and 8 in the sequence of the HLA-A2-restricted human T-lymphotrophic virus type I Tax peptide. Cyclic peptides promoted the in vitro folding and assembly of HLA-A2 complexes. Thermal denaturation studies using circular dichroism spectroscopy showed that these complexes are as stable as complexes formed with antigenic peptides. Images Fig. 2 Fig. 4 PMID:8643447

Effect of PEGylation on drug entry into lipid bilayer.

PubMed

Rissanen, Sami; Kumorek, Marta; Martinez-Seara, Hector; Li, Yen-Chin; Jamróz, Dorota; Bunker, Alex; Nowakowska, Maria; Vattulainen, Ilpo; Kepczynski, Mariusz; Róg, Tomasz

2014-01-09

Poly(ethylene glycol) (PEG) is a polymer commonly used for functionalization of drug molecules to increase their bloodstream lifetime, hence efficacy. However, the interactions between the PEGylated drugs and biomembranes are not clearly understood. In this study, we employed atomic-scale molecular dynamics (MD) simulations to consider the behavior of two drug molecules functionalized with PEG (tetraphenylporphyrin used in cancer phototherapy and biochanin A belonging to the isoflavone family) in the presence of a lipid bilayer. The commonly held view is that functionalization of a drug molecule with a polymer acts as an entropic barrier, inhibiting the penetration of the drug molecule through a cell membrane. Our results indicate that in the bloodstream there is an additional source of electrostatic repulsive interactions between the PEGylated drugs and the lipid bilayer. Both the PEG chain and lipids can bind Na(+) ions, thus effectively becoming positively charged molecules. This leads to an extra repulsive effect resulting from the presence of salt in the bloodstream. Thus, our study sheds further light on the role of PEG in drug delivery.

Thermodynamic phase behavior of API/polymer solid dispersions.

PubMed

Prudic, Anke; Ji, Yuanhui; Sadowski, Gabriele

2014-07-07

To improve the bioavailability of poorly soluble active pharmaceutical ingredients (APIs), these materials are often integrated into a polymer matrix that acts as a carrier. The resulting mixture is called a solid dispersion. In this work, the phase behaviors of solid dispersions were investigated as a function of the API as well as of the type and molecular weight of the carrier polymer. Specifically, the solubility of artemisinin and indomethacin was measured in different poly(ethylene glycol)s (PEG 400, PEG 6000, and PEG 35000). The measured solubility data and the solubility of sulfonamides in poly(vinylpyrrolidone) (PVP) K10 and PEG 35000 were modeled using the perturbed-chain statistical associating fluid theory (PC-SAFT). The results show that PC-SAFT predictions are in a good accordance with the experimental data, and PC-SAFT can be used to predict the whole phase diagram of an API/polymer solid dispersion as a function of the kind of API and polymer and of the polymer's molecular weight. This remarkably simplifies the screening process for suitable API/polymer combinations.

Hydrogel Design for Supporting Neurite Outgrowth and Promoting Gene Delivery to Maximize Neurite Extension

PubMed Central

Shepard, Jaclyn A.; Stevans, Alyson C.; Holland, Samantha; Wang, Christine E.; Shikanov, Ariella; Shea, Lonnie D.

2012-01-01

Hydrogels capable of gene delivery provide a combinatorial approach for nerve regeneration, with the hydrogel supporting neurite outgrowth and gene delivery inducing the expression of inductive factors. This report investigates the design of hydrogels that balance the requirements for supporting neurite growth with those requirements for promoting gene delivery. Enzymatically-degradable PEG hydrogels encapsulating dorsal root ganglia explants, fibroblasts, and lipoplexes encoding nerve growth factor were gelled within channels that can physically guide neurite outgrowth. Transfection of fibroblasts increased with increasing concentration of Arg-Gly-Asp (RGD) cell adhesion sites and decreasing PEG content. The neurite length increased with increasing RGD concentration within 10% PEG hydrogels, yet was maximal within 7.5% PEG hydrogels at intermediate RGD levels. Delivering lipoplexes within the gel produced longer neurites than culture in NGF-supplemented media or co-culture with cells exposed to DNA prior to encapsulation. Hydrogels designed to support neurite outgrowth and deliver gene therapy vectors locally may ultimately be employed to address multiple barriers that limit regeneration. PMID:22038654

Indocyanine Green-Encapsulated Hybrid Polymeric Nanomicelles for Photothermal Cancer Therapy.

PubMed

Jian, Wei-Hong; Yu, Ting-Wei; Chen, Chien-Ju; Huang, Wen-Chia; Chiu, Hsin-Cheng; Chiang, Wen-Hsuan

2015-06-09

Indocyanine green (ICG), an FDA approved medical near-infrared (NIR) imaging agent, has been extensively used in cancer theranosis. However, the limited aqueous photostability, rapid body clearance, and poor cellular uptake severely restrict its practical applications. For these problems to be overcome, ICG-encapsulated hybrid polymeric nanomicelles (PNMs) were developed in this work through coassociation of the amphiphilic diblock copolymer poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG) and hydrophobic electrostatic complexes composed of ICG molecules and branched poly(ethylenimine) (PEI). The ICG-encapsulated hybrid PNMs featured a hydrophobic PLGA/ICG/PEI core stabilized by hydrophilic PEG shells. The encapsulation of electrostatic ICG/PEI complexes into the compact PLGA-rich core not only facilitated the ICG loading but also promoted its aqueous optical stability. The effects of the chain length of PEI in combination with ICG on the physiochemical properties of PNMs and their drug leakage were also investigated. PEI(10k) (10 kDa) could form highly robust and dense complexes with ICG, and thus prominently reduced ICG outflow from the PNMs. The results of in vitro cellular uptake and cytotoxicity studies revealed that the ICG/PEI(10k)-loaded PNMs significantly promoted cellular uptake of ICG by HeLa cells due to their near-neutral surface, and thereby augmented the NIR-triggered hyperthermia effect in destroying cancer cells. These findings strongly indicate that the ICG/PEI10k-loaded PNMs have significant potential for attaining effective cancer imaging and photothermal therapy.

Zwitterionic lipid assemblies: Molecular dynamics studies of monolayers, bilayers, and vesicles using a new coarse grain force field

PubMed Central

Shinoda, Wataru; DeVane, Russell; Klein, Michael L.

2010-01-01

A new coarse-grained (CG) intermolecular force field is presented for a series of zwitterionic lipids. The model is an extension of our previous work on nonionic surfactants and is designed to reproduce experimental surface/interfacial properties as well as distribution functions from all-atom molecular dynamics (MD) simulations. Using simple functional forms, the force field parameters are optimized for multiple lipid molecules, simultaneously. The resulting CG lipid bilayers have reasonable molecular areas, chain order parameters, and elastic properties. The computed surface pressure vs. area (π-A) curve for a DPPC monolayer demonstrates a significant improvement over the previous CG models. The DPPC monolayer has a longer persistence length than a PEG lipid monolayer, exhibiting a long-lived curved monolayer surface under negative tension. The bud ejected from an oversaturated DPPC monolayer has a large bicelle-like structure, which is different from the micellar bud formed from an oversaturated PEG lipid monolayer. We have successfully observed vesicle formation during CG-MD simulations, starting from an aggregate of DMPC molecules. Depending on the aggregate size, the lipid assembly spontaneously transforms into a closed vesicle or a bicelle. None of the various intermediate structures between these extremes seem to be stable. An attempt to observe fusion of two vesicles through the application of an external adhesion force was not successful. The present CG force field also supports stable multi-lamellar DMPC vesicles. PMID:20438090

A novel photoacoustic nanoprobe of ICG@PEG-Ag2S for atherosclerosis targeting and imaging in vivo

NASA Astrophysics Data System (ADS)

Wu, Chenxin; Zhang, Yejun; Li, Zhen; Li, Chunyan; Wang, Qiangbin

2016-06-01

Atherosclerosis is a major cause of cardiovascular and cerebrovascular diseases that have high mortality and disability rates. Because of its unclear pathogenic mechanism and heterogeneous distribution feature, it is still a big challenge to achieve precise diagnosis and therapy of atherosclerosis at its early stage in vivo. Herein, we fabricated a new ICG@PEG-Ag2S nanoprobe by a simple self-assembly of DT-Ag2S QDs, amphipathic C18/PEG polymer molecules and ICG. The ICG@PEG-Ag2S nanoprobe showed relatively long blood retention and was selectively accumulated in the region of atherosclerotic plaque due to the lipophilicity of the C18 chain to the atherosclerosis microenvironment, and thus the atherosclerosis was real-time monitored by high contrast-enhanced photoacoustic (PA) imaging of ICG. Combining the high signal-to-noise ratio (SNR) and high spatial resolution fluorescence imaging of Ag2S QDs in the second near-infrared window (NIR-II) and related histological assessment in vitro, the feasibility of this new nanoprobe for atherosclerosis targeting in an Apoe-/- mouse model was verified. Additionally, hemolysis and coagulation assays of the ICG@PEG-Ag2S revealed its decent hemocompatibility and no histological changes were observed in the main organs of the mouse. Such a simple, multifunctional nanoprobe for targeting and PA imaging of atherosclerosis will have a great potential for future clinical applications.Atherosclerosis is a major cause of cardiovascular and cerebrovascular diseases that have high mortality and disability rates. Because of its unclear pathogenic mechanism and heterogeneous distribution feature, it is still a big challenge to achieve precise diagnosis and therapy of atherosclerosis at its early stage in vivo. Herein, we fabricated a new ICG@PEG-Ag2S nanoprobe by a simple self-assembly of DT-Ag2S QDs, amphipathic C18/PEG polymer molecules and ICG. The ICG@PEG-Ag2S nanoprobe showed relatively long blood retention and was selectively accumulated in the region of atherosclerotic plaque due to the lipophilicity of the C18 chain to the atherosclerosis microenvironment, and thus the atherosclerosis was real-time monitored by high contrast-enhanced photoacoustic (PA) imaging of ICG. Combining the high signal-to-noise ratio (SNR) and high spatial resolution fluorescence imaging of Ag2S QDs in the second near-infrared window (NIR-II) and related histological assessment in vitro, the feasibility of this new nanoprobe for atherosclerosis targeting in an Apoe-/- mouse model was verified. Additionally, hemolysis and coagulation assays of the ICG@PEG-Ag2S revealed its decent hemocompatibility and no histological changes were observed in the main organs of the mouse. Such a simple, multifunctional nanoprobe for targeting and PA imaging of atherosclerosis will have a great potential for future clinical applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00060f

The rational design of recognitive polymeric networks for sensing applications

NASA Astrophysics Data System (ADS)

Noss, Kimberly Ryanne Dial

Testosterone recognitive networks were synthesized with varying feed crosslinking percentages and length of the bi-functional crosslinking agent to analyze the effect of changing structural parameters on template binding properties such as affinity, selectivity, capacity, and diffusional transport. The crosslinking percentage of the crosslinking monomer ethylene glycol dimethacrylate was varied from 50% to 90% and associated networks experienced a 2 fold increase in capacity and a 4 fold increase in affinity with the equilibrium association constants, Ka, ranging from 0.32 +/- 0.02 x 10 4 M-1 to 1.3 +/- 0.1 x 104 M -1, respectively. The higher concentration of crosslinking monomer increased the crosslinking points available for inter-chain stabilization creating an increased number of stable cavities for template association. However, by increasing the length of the crosslinking agent and increasing the feed crosslinking percentage from 77% crosslinked poly(methacrylic acid- co-ethylene glycol dimethacrylate) (poly(MAA-co-EGDMA)) to 50% crosslinked poly(methacrylic acid-co-poly(ethylene glycol)200 dimethacrylate) (poly(MAA-co-PEG200DMA)), the mesh size of the network increased resulting in an increased template diffusion coefficient from (2.83 +/- 0.06) x 109 cm2/s to (4.3 +/- 0.06) x 109 cm2/s, respectively, which is approximately a 40% faster template diffussional transport. A 77% crosslinked poly (MAA-co-PEG200DMA) recognitive network had an association constant of (0.20 +/- 0.05) x 104 M -1 and bound (0.72 +/- 0.04) x 10-2 mmol testosterone/g dry polymer, which was less by 6 and 3 fold, respectively, compared to a similarly crosslinked poly(MAA-co-EGDMA) recognitive network. Structural manipulation of the macromolecular architecture illustrates the programmability of recognitive networks for specific template binding parameters and diffusional transport, which may lead to enhanced imprinted sensor materials and successful integration onto sensor platforms.

New insights into transcription fidelity: thermal stability of non-canonical structures in template DNA regulates transcriptional arrest, pause, and slippage.

PubMed

Tateishi-Karimata, Hisae; Isono, Noburu; Sugimoto, Naoki

2014-01-01

The thermal stability and topology of non-canonical structures of G-quadruplexes and hairpins in template DNA were investigated, and the effect of non-canonical structures on transcription fidelity was evaluated quantitatively. We designed ten template DNAs: A linear sequence that does not have significant higher-order structure, three sequences that form hairpin structures, and six sequences that form G-quadruplex structures with different stabilities. Templates with non-canonical structures induced the production of an arrested, a slipped, and a full-length transcript, whereas the linear sequence produced only a full-length transcript. The efficiency of production for run-off transcripts (full-length and slipped transcripts) from templates that formed the non-canonical structures was lower than that from the linear. G-quadruplex structures were more effective inhibitors of full-length product formation than were hairpin structure even when the stability of the G-quadruplex in an aqueous solution was the same as that of the hairpin. We considered that intra-polymerase conditions may differentially affect the stability of non-canonical structures. The values of transcription efficiencies of run-off or arrest transcripts were correlated with stabilities of non-canonical structures in the intra-polymerase condition mimicked by 20 wt% polyethylene glycol (PEG). Transcriptional arrest was induced when the stability of the G-quadruplex structure (-ΔG°37) in the presence of 20 wt% PEG was more than 8.2 kcal mol(-1). Thus, values of stability in the presence of 20 wt% PEG are an important indicator of transcription perturbation. Our results further our understanding of the impact of template structure on the transcription process and may guide logical design of transcription-regulating drugs.

New Insights into Transcription Fidelity: Thermal Stability of Non-Canonical Structures in Template DNA Regulates Transcriptional Arrest, Pause, and Slippage

PubMed Central

Tateishi-Karimata, Hisae; Isono, Noburu; Sugimoto, Naoki

2014-01-01

The thermal stability and topology of non-canonical structures of G-quadruplexes and hairpins in template DNA were investigated, and the effect of non-canonical structures on transcription fidelity was evaluated quantitatively. We designed ten template DNAs: A linear sequence that does not have significant higher-order structure, three sequences that form hairpin structures, and six sequences that form G-quadruplex structures with different stabilities. Templates with non-canonical structures induced the production of an arrested, a slipped, and a full-length transcript, whereas the linear sequence produced only a full-length transcript. The efficiency of production for run-off transcripts (full-length and slipped transcripts) from templates that formed the non-canonical structures was lower than that from the linear. G-quadruplex structures were more effective inhibitors of full-length product formation than were hairpin structure even when the stability of the G-quadruplex in an aqueous solution was the same as that of the hairpin. We considered that intra-polymerase conditions may differentially affect the stability of non-canonical structures. The values of transcription efficiencies of run-off or arrest transcripts were correlated with stabilities of non-canonical structures in the intra-polymerase condition mimicked by 20 wt% polyethylene glycol (PEG). Transcriptional arrest was induced when the stability of the G-quadruplex structure (−ΔGo 37) in the presence of 20 wt% PEG was more than 8.2 kcal mol−1. Thus, values of stability in the presence of 20 wt% PEG are an important indicator of transcription perturbation. Our results further our understanding of the impact of template structure on the transcription process and may guide logical design of transcription-regulating drugs. PMID:24594642

Development of a novel folate-modified nanobubbles with improved targeting ability to tumor cells.

PubMed

Duan, Sujuan; Guo, Lu; Shi, Dandan; Shang, Mengmeng; Meng, Dong; Li, Jie

2017-07-01

Conjugation of folate (FOL) to nanobubbles could enhance the selective targeting to tumors expressing high levels of folate receptor (FR). To further improve the selective targeting ability of FOL-modified nanobubbles, a novel FOL-targeted nanobubble ((FOL) 2 -NB) with increasing FOL content (accomplished by linking two FOL molecules per DSPE-PEG2000 chain) was synthesized, through the methods of mechanical shaking and low-speed centrifugation based on lipid-stabilized perfluoropropane. The bubble size and distribution range were measured by dynamic light scattering (DLS). Enhanced imaging ability was evaluated using a custom-made agarose mold with a clinical US imaging system at mechanical indices of up to 0.12 at a center frequency of 9.0MHz. Targeted ability was also carried out in human breast cancer MCF-7 cells, which over-express the FR, by fluorescence activated cell sorting (FACS) and fluorescence microscopy, respectively. (FOL) 2 -NB with a particle size of 286.87±22.96nm were successfully prepared, and they exhibited superior contrast imaging effect. FACS and fluorescence microscopy studies showed greater cellular targeting ability in the group of (FOL) 2 -NB than in their control group of Non-targeted-NB (no FOL targeted nanobubbles) and FOL-NB (one FOL molecule per DSPE-PEG2000 chain). These results suggest that a new type of stronger targeted nanobubble was successfully prepared by increasing the FOL content per DSPE-PEG2000 chain. This novel (FOL) 2 -NBs are potentially useful for ultrasound molecular imaging and treatment of FR-positive tumors and are worthy for further investigation. Copyright © 2017 Elsevier B.V. All rights reserved.

Biometrical analysis of the shoulder joint regarding glenoid implant dimensions for arthroplasty.

PubMed

Kircher, Jörn; Bittersohl, Bernd; Zilkens, Christoph; Hedtmann, Achim; Krauspe, Rüdiger

2014-05-01

Reduced bone stock and difficult intraoperative orientation are challenges in glenoid replacement surgery. New implant designs and methods for fixation, such as locking screws, extra-long central pegs and/or central compression screws are targeting these issues. The objective of this study is the analysis of the glenoid dimension regarding maximum central peg diameter and peg length (PL), and maximum screw length (SL) for glenoid fixation. Retrospective analysis of magnetic resonance imaging (n = 50) scans. Measurement of the maximum inferior glenoid diameter (GD), SL, maximum length of a 9.9, 10 and 11.4 mm central peg (PL) in the transverse plane; glenoid version (GV), humeral head diameter (HHD). Two independent measurements. Mean age: 49.0 ± 15.7 years (17-80) (n = 20 female, 49.6 ± 16.0; n = 30 male, 48.6 ± 15.7). Mean values of measurement were GD: 28.9 ± 3.7 mm (21-39); SL: 34.1 ± 4.9 mm (26-44); PL 9.9 mm: 19.4 ± 4.3 mm (9-30); PL 10 mm: 19.0 ± 4.4 mm (8-30); PL 11.4 mm: 16.5 ± 4.1 mm (7-26) with significant gender differences (p = 0.001; p = 0.022; p = 0.001); GV: -0.6° ± 4.9° (-10 to 11); HHD: 50.0 mm ± 4.9 (41-61). There was good correlation between PL and SL (r = 0.32, p = 0.024) and for GD and PL (r = 0.61, p = 0.001; r = 0.57, p = 0.001; r = 0.96, p = 0.001). The ratio of HHD and GD was very constant with 0.6 ± 0.07. These data indicate the high interindividual variability of glenoid morphology including significant gender-related differences. The good correlation between humeral head size and GD and maximum central PL can be helpful for cases with reduced bone stock in decision-making about implant size and bone grafting.

Macroscopic and tunable nanoparticle superlattices

DOE PAGES

Zhang, Honghu; Wang, Wenjie; Mallapragada, Surya; ...

2016-10-24

In this paper, we describe a robust method to assemble nanoparticles into highly ordered superlattices by inducing aqueous phase separation of neutral capping polymers. Here we demonstrate the approach with thiolated polyethylene-glycol-functionalized gold nanoparticles (PEG-AuNPs) in the presence of salts (for example, K 2CO 3) in solutions that spontaneously migrate to the liquid–vapor interface to form a Gibbs monolayer. We show that by increasing salt concentration, PEG-AuNP monolayers transform from two-dimensional (2D) gas-like to liquid-like phase and eventually, beyond a threshold concentration, to a highly ordered hexagonal structure, as characterized by surface sensitive synchrotron X-ray reflectivity and grazing incidence X-raymore » diffraction. Furthermore, the method allows control of the inplane packing in the crystalline phase by varying the K 2CO 3 and PEG-AuNPs concentrations and the length of PEG. Using polymer-brush theory, we argue that the assembly and crystallization is driven by the need to reduce surface tension between PEG and the salt solution. Our approach of taking advantage of the phase separation of PEG in salt solutions is general (i.e., can be used with any nanoparticles) leads to high-quality macroscopic and tunable crystals. In conclusion, we discuss how the method can also be applied to the design of orderly 3D structures.« less

SS-mPEG chemical modification of recombinant phospholipase C for enhanced thermal stability and catalytic efficiency.

PubMed

Fang, Xian; Wang, Xueting; Li, Guiling; Zeng, Jun; Li, Jian; Liu, Jingwen

2018-05-01

PEGylation is one of the most promising and extensively studied strategies for improving the properties of proteins as well as enzymic physical and thermal stability. Phospholipase C, hydrolyzing the phospholipids offers tremendous applications in diverse fields. However, the poor thermal stability and higher cost of production have restricted its industrial application. This study focused on improving the stabilization of recombinant PLC by chemical modification with methoxypolyethylene glycol-Succinimidyl Succinate (SS-mPEG, MW 5000). PLC gene from isolate Bacillus cereus HSL3 was fused with SUMO, a novel small ubiquitin-related modifier expression vector and over expressed in Escherichia coli. The soluble fraction of SUMO-PLC reached 80% of the total recombinant protein. The enzyme exhibited maximum catalytic activity at 80 °C and was relatively thermostable at 40-70 °C. It showed extensive substrate specificity pattern and marked activity toward phosphatidylcholine, which made it a typical non-specific PLC for industrial purpose. SS-mPEG-PLC complex exhibited an enhanced thermal stability at 70-80 °C and the catalytic efficiency (K cat /K m ) had increased by 3.03 folds compared with free PLC. CD spectrum of SS-mPEG-PLC indicated a possible enzyme aggregation after chemical modification, which contributed to the higher thermostability of SS-mPEG-PLC. The increase of antiparallel β sheets in secondary structure also made it more stable than parallel β sheets. The presence of SS-mPEG chains on the enzyme molecule surface somewhat changed the binding rate of the substrates, leading to a significant improvement in catalytic efficiency. This study provided an insight into the addition of SS-mPEG for enhancing the industrial applications of phospholipase C at higher temperature. Copyright © 2018 Elsevier B.V. All rights reserved.

Combination cancer therapy by hapten-targeted prodrug-activating enzymes and cytokines.

PubMed

Chuang, Kuo-Hsiang; Cheng, Chiu-Min; Roffler, Steve R; Lu, Yu-Lin; Lin, Shiu-Ru; Wang, Jaw-Yuan; Tzou, Wen-Shyong; Su, Yu-Cheng; Chen, Bing-Mae; Cheng, Tian-Lu

2006-01-01

Combination therapy can help overcome limitations in the treatment of heterogeneous tumors. In the current study, we examined whether multiple therapeutic agents could be targeted to anti-dansyl single-chain antibodies (DNS scFv) that were anchored on the plasma membrane of cancer cells. Functional DNS scFv could be stably expressed on CT-26 colon cancer cells both in vitro and in vivo. Dansyl moieties were covalently attached to recombinant beta-glucuronidase (betaG) and interleukin 2 (IL-2) via a flexible poly(ethylene glycol) linker to form DNS-PEG-betaG and DNS-PEG-IL-2 conjugates. The conjugates displayed enzymatic and splenocyte-stimulatory activities, respectively, that were similar to those of the unmodified proteins. The conjugates selectively bound CT-26 cells that expressed anti-DNS scFv (CT-26/DNS cells) but not CT-26 cells that expressed control scFv (CT-26/phOx cells). DNS-PEG-betaG preferentially activated a glucuronide prodrug (BHAMG) of p-hydroxy aniline mustard at CT-26/DNS cells in culture and accumulated in subcutaneous CT-26/DNS tumors after intravenous administration. Systemic administration of DNS-PEG-IL-2 or DNS-PEG-betaG and BHAMG significantly delayed the growth of CT-26/DNS but not control CT-26/phOx tumors. Combination treatment with DNS-PEG-betaG and BHAMG followed by DNS-PEG-IL-2 therapy significantly suppressed the growth of CT-26/DNS tumors as compared to either single-agent regimen. These results show that at least two DNS-modified therapeutic agents can be selectively delivered to DNS scFv receptors in vitro and in vivo, allowing combination therapy of DNS scFv-modified tumors.

Effects of pistachio by-products on digestibility, milk production, milk fatty acid profile and blood metabolites in Saanen dairy goats.

PubMed

Sedighi-Vesagh, R; Naserian, A A; Ghaffari, M H; Petit, H V

2015-08-01

The objective of this study was to investigate the effects of pistachio by-products (PBP) on nutrient digestibility, blood metabolites and milk fatty acid (FA) profile in Saanen dairy goats. Nine multiparous lactating Saanen goats (on day 90 post-partum, 45 ± 2/kg BW) were randomly assigned to a 3 × 3 Latin square design with three treatment diets: 1) control diet (alfalfa hay based), 2) 32% PBP and 3) 32% PBP + polyethylene glycol (PEG-4000; 1 g/kg dry matter). Each period lasted 21 days, including 14 day for treatment adaptation and 7 day for data collection. Pistachio by-products significantly decreased (p < 0.01) crude protein (CP) digestibility compared with the control diet (64.4% vs. 58.7%), but PEG addition did not differ for CP digestibility of goats fed 32% PBP + PEG and those fed the two other diets. The digestibility of NDF tended (p = 0.06) to decrease for goats fed PBP compared with those fed the control diet. Yields of milk and 4% fat-corrected milk were not affected by dietary treatments. Compared with the control diet, PBP supplementation appreciably changed the proportions of almost all the milk FA measured; the main effects were decreases (p < 0.01) in FA from 8:0 to 16:0 and increases (p < 0.01) proportions of cis-9, trans-11 18:2 and trans-11 18:1, monounsaturated FA, polyunsaturated FA and long-chain FA. The saturated FA, short-chain FA and medium-chain FA proportions were lower (p < 0.01) in goats fed the two PBP supplemented diet than in those fed the control diet and PEG addition led to intermediate proportions of saturated FA, unsaturated and monounsaturated FA. Inclusion of PBP in the diet decreased (p < 0.01) plasma concentrations of glucose and urea nitrogen compared with the control diet. It was concluded that PBP can be used as forage in the diet of dairy goats without interfering with milk yield. Inclusion of 32% PBP in the diet of dairy goats had beneficial effects on milk FA profile but PEG addition to PBP did not contribute to enhance further milk FA profile. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

α-chymotrypsin activated and stabilized by self-assembled polypseudorotaxane fabricated with bis-thiolated poly(ethylene glycol) and α-cyclodextrin: Spectroscopic and mechanistic analysis.

PubMed

Zhao, Jun; Lin, Ji-Duan; Chen, Jia-Chen; Chen, Guo; Li, Xia-Lan; Wang, Xiao-Qin; Chen, Ming-Xia

2017-09-01

The self-assembled polypseudorotaxane (PPRX) fabricated with bis-thiolated poly(ethylene glycol) (PEG) and α-cyclodextrin (α-CyD) acted as an activator for α-chymotrypsin (CT) and retained the activity of CT for a long time up to 7days. The stabilization mechanism was studied, and the interaction between CT and PPRX was analyzed by using circular dichroism, fluorescence spectra and X-ray powder diffraction (XRD). The bis-thiolated PEG and its assembled PPRX with α-CyD exhibited the interaction with the C-terminal region of the CT's B-chain probably through PEGylation of the surface disulfide bridge of CT. It caused the aromatic chromophores more exposed to the hydrophilic microenvironment, leading to conformational variation of CT that was revealed by spectroscopic analysis. It rendered the peptide chains in a more flexible and active state. As a comparison, the non-thiolated components could not decorate the surface of CT and performed almost no effect on its stability, which demonstrated that the decoration of the surface disulfide bridge was a key factor in retaining the activity of CT. Due to the activation and stabilization effect, bis-thiolated PEG/α-CyD PPRX was an excellent soft-immobilized carrier for CT, and provided an intriguing method for enzyme's stabilization. Copyright © 2017 Elsevier B.V. All rights reserved.

Silica Encapsulated Gold Nanoparticles as SERS Labels for the Detection of Lymphoma B-Cells in Tissue Sections

NASA Astrophysics Data System (ADS)

Al-Faouri, Tamara

The surface of silica encapsulated gold nanoparticles with trans-1,2-bis (4-pyridyl) ethylene Raman active dye were utilized as SERS labels to target CD20 surface protein on lymphoma B-cells in human tissue sections with CLL or FL. SERS labels were functionalized with various antibody linkers including carboxylic, aldehyde, and heterobifunctional PEG chains with an NHS end, to permit them to bind to tissue section samples. NP samples and tissue sections were characterized through UV-Vis spectroscopy, TEM, XPS, Zeta potential measurements, Dark Field microscopy, Raman spectroscopy, NMR, and AFM. The number of SERS labels present on a tissue sample was estimated using dark field images and a particle counting software. It was found that the heterobifunctional PEG chains linker provided the most specific binding of SERS labels with an estimated NP count of 1.33x106 NPs on the whole tissue and produced the highest Raman scatter intensity of approximately 48600 counts.

pH-Responsive biodegradable polymeric micelles with anchors to interface magnetic nanoparticles for MR imaging in detection of cerebral ischemic area

NASA Astrophysics Data System (ADS)

Yang, Hong Yu; Jang, Moon-Sun; Gao, Guang Hui; Lee, Jung Hee; Lee, Doo Sung

2016-06-01

A novel type of pH-responsive biodegradable copolymer was developed based on methyloxy-poly(ethylene glycol)-block-poly[dopamine-2-(dibutylamino) ethylamine-l-glutamate] (mPEG-b-P(DPA-DE)LG) and applied to act as an intelligent nanocarrier system for magnetic resonance imaging (MRI). The mPEG-b-P(DPA-DE)LG copolymer was synthesized by a typical ring opening polymerization of N-carboxyanhydrides (NCAs-ROP) using mPEG-NH2 as a macroinitiator, and two types of amine-terminated dopamine groups and pH-sensitive ligands were grafted onto a side chain by a sequential aminolysis reaction. This design greatly benefits from the addition of the dopamine groups to facilitate self-assembly, as these groups can act as high-affinity anchors for iron oxide nanoparticles, thereby increasing long-term stability at physiological pH. The mPEG moiety in the copolymers helped the nanoparticles to remain well-dispersed in an aqueous solution, and pH-responsive groups could control the release of hydrophobic Fe3O4 nanoparticles in an acidic environment. The particle size of the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles was measured by dynamic light scattering (DLS) and cryo-TEM. The superparamagnetic properties of the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles were confirmed by a superconducting quantum interference device (SQUID). T2-weighted magnetic resonance imaging (MRI) of Fe3O4-loaded mPEG-b-P(DPA-DE)LG phantoms exhibited enhanced negative contrast with an r2 relaxivity of approximately 106.7 mM-1 s-1. To assess the ability of the Fe3O4-loaded mPEG-P(DE-DPA)LG micelles to act as MRI probes, we utilized a cerebral ischemia disease rat model with acidic tissue. We found that a gradual change in contrast in the cerebral ischemic area could be visualized by MRI after 1 h, and maximal signal loss was detected after 24 h post-injection. These results demonstrated that the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles can act as pH-triggered MRI probes for diagnostic imaging of acidic pathological tissues.A novel type of pH-responsive biodegradable copolymer was developed based on methyloxy-poly(ethylene glycol)-block-poly[dopamine-2-(dibutylamino) ethylamine-l-glutamate] (mPEG-b-P(DPA-DE)LG) and applied to act as an intelligent nanocarrier system for magnetic resonance imaging (MRI). The mPEG-b-P(DPA-DE)LG copolymer was synthesized by a typical ring opening polymerization of N-carboxyanhydrides (NCAs-ROP) using mPEG-NH2 as a macroinitiator, and two types of amine-terminated dopamine groups and pH-sensitive ligands were grafted onto a side chain by a sequential aminolysis reaction. This design greatly benefits from the addition of the dopamine groups to facilitate self-assembly, as these groups can act as high-affinity anchors for iron oxide nanoparticles, thereby increasing long-term stability at physiological pH. The mPEG moiety in the copolymers helped the nanoparticles to remain well-dispersed in an aqueous solution, and pH-responsive groups could control the release of hydrophobic Fe3O4 nanoparticles in an acidic environment. The particle size of the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles was measured by dynamic light scattering (DLS) and cryo-TEM. The superparamagnetic properties of the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles were confirmed by a superconducting quantum interference device (SQUID). T2-weighted magnetic resonance imaging (MRI) of Fe3O4-loaded mPEG-b-P(DPA-DE)LG phantoms exhibited enhanced negative contrast with an r2 relaxivity of approximately 106.7 mM-1 s-1. To assess the ability of the Fe3O4-loaded mPEG-P(DE-DPA)LG micelles to act as MRI probes, we utilized a cerebral ischemia disease rat model with acidic tissue. We found that a gradual change in contrast in the cerebral ischemic area could be visualized by MRI after 1 h, and maximal signal loss was detected after 24 h post-injection. These results demonstrated that the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles can act as pH-triggered MRI probes for diagnostic imaging of acidic pathological tissues. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06542a

Swelling of biological and semiflexible polyelectrolytes.

PubMed

Dobrynin, Andrey V; Carrillo, Jan-Michael Y

2009-10-21

We have developed a theoretical model of swelling of semiflexible (biological) polyelectrolytes in salt solutions. Our approach is based on separation of length scales which allowed us to split a chain's electrostatic energy into two parts that describe local and remote electrostatic interactions along the polymer backbone. The local part takes into account interactions between charged monomers that are separated by distances along the polymer backbone shorter than the chain's persistence length. These electrostatic interactions renormalize chain persistence length. The second part includes electrostatic interactions between remote charged pairs along the polymer backbone located at distances larger than the chain persistence length. These interactions are responsible for chain swelling. In the framework of this approach we calculated effective chain persistence length and chain size as a function of the Debye screening length, chain degree of ionization, bare persistence length and chain degree of polymerization. Our crossover expression for the effective chain's persistence length is in good quantitative agreement with the experimental data on DNA. We have been able to fit experimental datasets by using two adjustable parameters: DNA ionization degree (α = 0.15-0.17) and a bare persistence length (l(p) = 40-44 nm).

Ferritin nanocontainers that self-direct in synthetic polymer systems

NASA Astrophysics Data System (ADS)

Sengonul, Merih C.

Currently, there are many approaches to introduce functionality into synthetic polymers. Among these, for example, are copolymerization, grafting, and blending methods. However, modifications made by such methods also change the thermodynamics and rheological properties of the polymer system of interest, and each new modification often requires a costly reoptimization of polymer processing. Such a reoptimalization would not be necessary if new functionality could be introduced via a container whose external surface is chemically and physically tuned to interact with the parent polymer. The contents of the container could then be changed without changing other important properties of the parent polymer. In this context this thesis project explores an innovative nanocontainer platform which can be introduced into phase-separating homopolymer blends. Ferritin is a naturally existing nanocontainer that can be used synthetically to package and selectively transport functional moieties to a particular phase that is either in the bulk or on the surface of a homopolymer blend system. The principal focus of this work centers on modifying the surface of wild ferritin to: (1) render modified ferritin soluble in a non-aqueous solvent; and (2) impart it with self-directing properties when exposed to a homopolymer blend surface or incorporated into the bulk of a homopolymer blend. Wild ferritin is water soluble, and this research project successfully modified wild ferritin by grafting either amine-functional poly(ethylene glycol) (PEG) or short-chain alkanes to carbodiimide activated carboxylate groups on ferritin's surface. Such modified ferritin is soluble in dichloromethane (DCM). Modification was confirmed by ion-exchange chromatography, zeta-potential measurements, and electrospray mass spectroscopy. FT-IR was used to quantify the extent of PEGylation of the reaction products through area ratios of the -C-O-C asymmetric stretching vibration of the grafted PEG chains to the carbonyl stretching vibration (amide I band) of the protein. The dimensionless grafting density after PEGylation was found to be 0.13 with 120 average grafted PEG chains per ferritin nanocontainer. Modified ferritin was used for bulk modification of a phase-separated polymer blend of poly(desaminotyrosyl tyrosine dodecyl ester carbonate) [PDTD] and PEG. TEM micrographs showed remarkable selectivity of PEGylated ferritin to PEG domains, while alkylated ferritin self-directs to the PDTD matrix. We explain this strong selectivity by the favourable interaction energies between the grafted and free matrix chains. In addition, both modified and wild ferritin were used for surface modification of the phase-separated homopolymer blend of PDTD and poly(ε-caprolactone) (PCL). At physiological pH wild ferritin selectively adsorbed onto the PDTD phase, while alkylated ferritin showed a striking selectivity to PCL phase. We attribute this behavior to the increase in protein's pI point above physiological pH after modification, which changes the electrostatic interactions between the ferritin and the polymer surface. Collectively, these results demonstrate the versatile use of ferritin as a model nanocontainer for the selective modification of surface and bulk properties of polymers.

The roles of productivity and ecosystem size in determining food chain length in tropical terrestrial ecosystems.

PubMed

Young, Hillary S; McCauley, Douglas J; Dunbar, Robert B; Hutson, Michael S; Ter-Kuile, Ana Miller; Dirzo, Rodolfo

2013-03-01

Many different drivers, including productivity, ecosystem size, and disturbance, have been considered to explain natural variation in the length of food chains. Much remains unknown about the role of these various drivers in determining food chain length, and particularly about the mechanisms by which they may operate in terrestrial ecosystems, which have quite different ecological constraints than aquatic environments, where most food chain length studies have been thus far conducted. In this study, we tested the relative importance of ecosystem size and productivity in influencing food chain length in a terrestrial setting. We determined that (1) there is no effect of ecosystem size or productive space on food chain length; (2) rather, food chain length increases strongly and linearly with productivity; and (3) the observed changes in food chain length are likely achieved through a combination of changes in predator size, predator behavior, and consumer diversity along gradients in productivity. These results lend new insight into the mechanisms by which productivity can drive changes in food chain length, point to potential for systematic differences in the drivers of food web structure between terrestrial and aquatic systems, and challenge us to consider how ecological context may control the drivers that shape food chain length.

Electron-beam-initiated polymerization of poly(ethylene glycol)-based wood impregnants.

PubMed

Trey, Stacy M; Netrval, Julia; Berglund, Lars; Johansson, Mats

2010-11-01

The current study demonstrates that methacrylate and acrylate poly(ethylene glycol) (PEG) functional oligomers can be effectively impregnated into wood blocks, and cured efficiently to high conversions without catalyst by e-beam radiation, allowing for less susceptibility to leaching, and favorable properties including higher Brinell hardness values. PEG based monomers were chosen because there is a long history of this water-soluble monomer being able to penetrate the cell wall, thus bulking it and decreasing the uptake of water which further protects the wood from fungal attack. Diacrylate, dimethacrylate, and dihydroxyl functional PEG of M(w) 550-575, of concentrations 0, 30, 60, and 100 wt % in water, were vacuum pressure impregnated into Scots Pine blocks of 15 × 25 × 50 mm in an effort to bulk the cell wall. The samples were then irradiated and compared with nonirradiated samples. It was shown by IR, DSC that the acrylate polymers were fully cured to much higher conversions than can be reached with conventional methods. Leaching studies indicated a much lower amount of oligomer loss from the cured vinyl functional PEG chains in comparison to hydroxyl functional PEG indicating a high degree of fastening of the polymer in the wood. The Brinell hardness indicated a significant increase in hardness to hardwood levels in the modified samples compared to the samples of hydroxyl functional PEG and uncured vinyl PEG samples, which actually became softer than the untreated Scots Pine. By monitoring the dimensions of the sample it was found by weight percent gain calculations (WPG %) that water helps to swell the wood structure and allow better access of the oligomers into the cell wall. Further, the cure shrinkage of the wood samples demonstrated infiltration of the oligomers into the cell wall as this was not observed for methyl methacrylate which is well-documented to remain in the lumen. However, dimensional stability of the vinyl polymer modified blocks when placed in water was not observed to the same extent as PEG.

Polymers for the stabilization and delivery of proteins topically and per os to the insect hemocoel through conjugation with aliphatic polyethylene glycol.

PubMed

Jeffers, Laura A; Shen, Hongyan; Bissinger, Brooke W; Khalil, Sayed; Gunnoe, T Brent; Roe, R Michael

2014-10-01

Co-feeding of aliphatic polyethylene glycol (PEG), phospholipase A2, anionic and ionic detergents, and amphipathic glycoside with bovine serum albumin (BSA) as a model protein to fourth stadium tobacco budworms, Heliothis virescens, did not affect the levels of BSA in the hemolymph. Covalent conjugation of small proteins like the decapeptide trypsin modulating oostatic factor (TMOF) to polyethylene glycol was previously shown to protect the peptide from protease attack and enhance its accumulation in the insect hemocoel. Whether this polymer chemistry could do the same for larger proteins was examined. The chemistry for the synthesis of polydispersed aliphatic PEG350-insulin and monodispersed aliphatic PEG333-insulin are described herein. Insulin was used for this synthesis and not BSA to better control conjugation among the available free amine groups. When PEGylated insulin or free insulin were fed in artificial diet to fifth stadium budworms, greater concentrations of insulin using the PEGylated variants were found in the hemolymph than when free insulin was used (a 6.7 and 7.3-fold increase for the PEG350 and PEG333 conjugates, respectively). When insulin is topically applied to the dorsum of H. virescens, no insulin is found in the hemolymph. However, after topical application of the PEGylated insulins, PEG350-insulin and PEG333-insulin were detected in the hemolymph. After injections of insulin into the hemocoel of fourth stadium H. virescens, insulin is completely cleared from the hemolymph in 120min. In comparison, PEG350-insulin and PEG333-insulin were present in the hemolymph for 300 and 240min after injection, respectively, translating to a 3.3 and 2.7-fold increase in the length of time insulin remains in the hemolymph after injection. Copyright © 2014 Elsevier Inc. All rights reserved.

Treatment of 9L gliosarcoma in rats by ferrociphenol-loaded lipid nanocapsules based on a passive targeting strategy via the EPR effect.

PubMed

Huynh, Ngoc Trinh; Morille, Marie; Bejaud, Jerome; Legras, Pierre; Vessieres, Anne; Jaouen, Gerard; Benoit, Jean-Pierre; Passirani, Catherine

2011-12-01

To study a passive targeting strategy, via the enhanced permeability and retention effect following systemic administration of lipid nanocapsules (LNCs) loaded with ferrociphenol, FcdiOH. Long chains of polyethylene glycol (DSPE-mPEG2000) were incorporated onto the surface of LNCs by post-insertion technique. Stealth properties of LNCs were investigated by in vitro complement consumption and macrophage uptake, and in vivo pharmacokinetics in healthy rats. Antitumour effect of FcdiOH-loaded LNCs was evaluated in subcutaneous and intracranial 9L gliosarcoma rat models. LNCs and DSPE-mPEG2000-LNCs presented low complement activation and weak macrophage uptake. DSPE-mPEG2000-LNCs exhibited prolonged half-life and extended area under the curve in healthy rats. In a subcutaneous gliosarcoma model, a single intravenous injection of FcdiOH-LNCs (400 μL, 2.4 mg/rat) considerably inhibited tumour growth when compared to the control. DSPE-mPEG2000-FcdiOH-LNCs exhibited a strong antitumour effect by nearly eradicating the tumour by the end of the study. In intracranial gliosarcoma model, treatment with DSPE-mPEG2000-FcdiOH-LNCs and FcdiOH-LNCs statistically improved median survival time (28 and 27.5 days, respectively) compared to the control (25 days). These results demonstrate the interesting perspectives for the systemic treatment of glioma thanks to bio-organometallic chemotherapy via lipid nanocapsules.

Seasonal regulation of condensed tannin consumption by free-ranging goats in a semi-arid savanna

PubMed Central

Heitkӧnig, Ignas M. A.; Scogings, Peter F.; Hattas, Dawood; Dziba, Luthando E.; Prins, Herbert H. T.; de Boer, Willem F.

2018-01-01

Although condensed tannins (CTs) are known to reduce forage intake by mammalian herbivores in controlled experiments, few studies have tested these effects in the field. Thus the role of CTs on foraging ecology of free-ranging herbivores is inadequately understood. To investigate the effects of CTs under natural savanna conditions, we pre-dosed groups of goats with polyethylene glycol (PEG, a CT-neutralising chemical), CT powder or water before observing their foraging behaviour. While accounting for the effects of season and time of the day, we tested the hypothesis that herbivores forage in ways that reduce the intake rate (g DM per minute) of CTs. We expected pre-dosing goats with CTs to reduce CT intake rates by (1) consuming diets low in CTs, (2) reducing bite rates, (3) increasing the number of foraging bouts, or (4) reducing the length of foraging bouts. Lastly, (5) expected CT to have no influence the number of dietary forage species. In both wet and dry seasons, pre-dosing goats with CTs resulted in lower CT consumption rates compared to PEG goats which seemed relieved from the stress associated with CT consumption. During dry season, the number of dietary forage species was similar across treatments, although goats that were dosed with PEG significantly increased this number in the wet season. Dosing goats with PEG increased the number and length of browsing bouts compared to goats from the other treatments. Pre-loading goats with PEG also tended to increase bite rates on browse forages, which contributed to increased consumption rates of CTs. Based on the behavioural adjustments made by goats in this study and within the constraints imposed by chemical complexity in savanna systems, we concluded that herbivores under natural conditions foraged in ways that minimised CTs consumption. More research should further elucidate the mechanism through which CTs regulated feeding behaviour. PMID:29293513

Face and Construct Validation of a Virtual Peg Transfer Simulator

PubMed Central

Arikatla, Venkata S; Sankaranarayanan, Ganesh; Ahn, Woojin; Chellali, Amine; De, Suvranu; Caroline, GL; Hwabejire, John; DeMoya, Marc; Schwaitzberg, Steven; Jones, Daniel B.

2013-01-01

Background The Fundamentals of Laparascopic Surgery (FLS) trainer box is now established as a standard for evaluating minimally invasive surgical skills. A particularly simple task in this trainer box is the peg transfer task which is aimed at testing the surgeon’s bimanual dexterity, hand-eye coordination, speed and precision. The Virtual Basic Laparoscopic Skill Trainer (VBLaST©) is a virtual version of the FLS tasks which allows automatic scoring and real time, subjective quantification of performance without the need of a human proctor. In this paper we report validation studies of the VBLaST© peg transfer (VBLaST-PT©) simulator. Methods Thirty-five subjects with medical background were divided into two groups: experts (PGY 4-5, fellows and practicing surgeons) and novices (PGY 1-3). The subjects were asked to perform the peg transfer task on both the FLS trainer box and the VBLaST-PT© simulator and their performance was evaluated based on established metrics of error and time. A new length of trajectory (LOT) metric has also been introduced for offline analysis. A questionnaire was used to rate the realism of the virtual system on a 5-point Likert scale. Results Preliminary face validation of the VBLaST-PT© with 34 subjects rated on a 5-point Likert scale questionnaire revealed high scores for all aspects of simulation, with 3.53 being the lowest mean score across all questions. A two-tailed Mann-Whitney performed on the total scores showed significant (p=0.001) difference between the groups. A similar test performed on the task time (p=0.002) and the length of trajectory (p=0.004) separately showed statistically significant differences between the experts and novice groups (p<0.05). The experts appear to be traversing shorter overall trajectories in less time than the novices. Conclusion VBLaST-PT© showed both face and construct validity and has promise as a substitute for the FLS to training peg transfer skills. PMID:23263645

Trehalose Glycopolymer Enhances Both Solution Stability and Pharmacokinetics of a Therapeutic Protein.

PubMed

Liu, Yang; Lee, Juneyoung; Mansfield, Kathryn M; Ko, Jeong Hoon; Sallam, Sahar; Wesdemiotis, Chrys; Maynard, Heather D

2017-03-15

Biocompatible polymers such as poly(ethylene glycol) (PEG) have been successfully conjugated to therapeutic proteins to enhance their pharmacokinetics. However, many of these polymers, including PEG, only improve the in vivo lifetimes and do not protect proteins against inactivation during storage and transportation. Herein, we report a polymer with trehalose side chains (PolyProtek) that is capable of improving both the external stability and the in vivo plasma half-life of a therapeutic protein. Insulin was employed as a model biologic, and high performance liquid chromatography and dynamic light scattering confirmed that addition of trehalose glycopolymer as an excipient or covalent conjugation prevented thermal or agitation-induced aggregation of insulin. The insulin-trehalose glycopolymer conjugate also showed significantly prolonged plasma circulation time in mice, similar to the analogous insulin-PEG conjugate. The insulin-trehalose glycopolymer conjugate was active as tested by insulin tolerance tests in mice and retained bioactivity even after exposure to high temperatures. The trehalose glycopolymer was shown to be nontoxic to mice up to at least 1.6 mg/kg dosage. These results together suggest that the trehalose glycopolymer should be further explored as an alternative to PEG for long circulating protein therapeutics.

Translational and rotational diffusion of flexible PEG and rigid dendrimer probes in sodium caseinate dispersions and acid gels.

PubMed

Salami, Souad; Rondeau-Mouro, Corinne; Barhoum, Myriam; van Duynhoven, John; Mariette, François

2014-09-01

The dynamics of rigid dendrimer and flexible PEG probes in sodium caseinate dispersions and acid gels, including both translational diffusion and rotational diffusion, were studied by NMR. Above the onset of the close-packing limit (C ∼ 10 g/100 g H2 O), translational diffusion of the probe depended on its flexibility and on the fluctuations of the matrix chains. The PEG probe diffused more rapidly than the spherical dendrimer probe of corresponding hydrodynamic radius. The greater conformational flexibility of PEG facilitated its motion through the crowded casein matrix. Rotational diffusion was, however, substantially less hindered than the translational diffusion and depended on the local protein-probe friction which became high when the casein concentration increased. The coagulation of the matrix led to the formation of large voids, which resulted in an increase in the translational diffusion of the probes, whereas the rotational diffusion of the probes was retarded in the gel, which could be attributed to the immobilized environment surrounding the probe. Quantitative information from PFG-NMR and SEM micrographs have been combined for characterizing microstructural details in SC acid gels. © 2014 Wiley Periodicals, Inc.

Development, Validation, and Application of a Novel Ligand-Binding Assay to Selectively Measure PEGylated Recombinant Human Coagulation Factor VIII (BAX 855).

PubMed

Weber, Alfred; Engelmaier, Andrea; Hainzelmayer, Sandra; Minibeck, Eva; Anderle, Heinz; Schwarz, Hans Peter; Turecek, Peter L

2015-10-21

BAX 855 is a PEGylated recombinant factor VIII preparation that showed prolonged circulatory half-life in nonclinical and clinical studies. This paper describes the development, validation, and application of a novel ligand-binding assay (LBA) to selectively measure BAX 855 in plasma. The LBA is based on PEG-specific capture of BAX 855, followed by immunological factor VIII (FVIII)-specific detection of the antibody-bound BAX 855. This assay principle enabled sensitive measurement of BAX 855 down to the low nanomolar range without interference from non-PEGylated FVIII as demonstrated by validation data for plasma from animals typically used for nonclinical characterization of FVIII. The selectivity of an in-house-developed anti-PEG and a commercially available preparation, shown by competition studies to primarily target the terminating methoxy group of PEG, also allowed assessment of the intactness of the attached PEG chains. Altogether, this new LBA adds to the group of methods to selectively, accurately, and precisely measure a PEGylated drug in complex biological matrices. The feasibility and convenience of using this method was demonstrated during extensive nonclinical characterization of BAX 855.

Enhancement of light absorption by blood to Nd:YAG laser using PEG-modified gold nanorods.

PubMed

Xing, Linzhuang; Li, Dong; Chen, Bin; Dai, Yuze; Wu, Wenjuan; Wang, Guoxiang

2016-10-01

On the basis of the principle of selective photothermolysis, laser therapy has been the most effective treatment strategy for Port-wine stains (PWSs) caused by the expansion of dermal capillaries. Neodymium:Yttrium Aluminum Garnet (Nd:YAG) laser at 1064 nm wavelength has great potential for deeply buried PWS, although its application is limited because of its weak absorption by blood. The purpose of this study is to investigate the effect of PEG-modified gold nanorods (NRs) on the blood absorption enhancement for Nd:YAG laser. PEG-modified gold nanorods (NRs) were synthesized via the seeded growth method. Then, the effect of PEG-modified gold NRs on blood light absorbance was investigated through adding different concentration of PEG-modified gold NRs to 1 ml of blood at room temperature. Finally, the optical properties of whole mice blood with or without PEG-modified gold NRs under slow heating were investigated. The average length and width of PEG-modified gold NRs are 79.5 ± 10.5 and 13.5 ± 0.9 nm, respectively, with the aspect ratio of 5.89, and a strong absorption peak exists at ∼1050 nm in the near-infrared range. A linear correlation between the blood absorbance at 1064 nm and the amount of PEG-modified gold NRs was obtained. The absorbance at 1064 nm increased 17.6, 33.0, 48.3, and 65.4 times when 0.4, 0.8, 1.2, and 1.6 mg of PEG-modified gold NRs was added to 1 ml of blood at room temperature, respectively. After adding 0.8 mg of PEG-modified gold NRs to 1 ml of blood, blood absorbance at 1064 nm at different temperatures increased by an average of 24.0 times. After intravenously injecting PEG-modified gold NRs (0.87 mg/ml) into Sprague-Dawley mice, the blood absorbance at 1064 nm increased from 0.014 to 0.5. Our findings suggest that PEG-modified gold NRs injection is an efficient way to enhance light absorption by blood to Nd:YAG laser. Lasers Surg. Med. 48:790-803, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Nanoscale Motion of Soft Nanoparticles in Unentangled and Entangled Polymer Matrices

NASA Astrophysics Data System (ADS)

Lungova, M.; Krutyeva, M.; Pyckhout-Hintzen, W.; Wischnewski, A.; Monkenbusch, M.; Allgaier, J.; Ohl, M.; Sharp, M.; Richter, D.

2016-09-01

We have studied the motion of polyhedral oligomeric silsesquioxane (POSS) nanoparticles modified with poly(ethylene glycol) (PEG) arms immersed in PEG matrices of different molecular weight. Employing neutron spin echo spectroscopy in combination with pulsed field gradient (PFG) NMR we found the following. (i) For entangled matrices the center of mass mean square displacement (MSD) of the PEG-POSS particles is subdiffusive following a t0.56 power law. (ii) The diffusion coefficient as well as the crossover to Fickian diffusion is independent of the matrix molecular weight and takes place as soon as the center of mass has moved a distance corresponding to the particle radius—this holds also for unentangled hosts. (iii) For the entangled matrices Rubinstein's scaling theory is validated; however, the numbers indicate that beyond Rouse friction the entanglement constraints appear to strongly increase the effective friction even on the nanoparticle length scale imposing a caveat on the interpretation of microrheological experiments. (iv) The oligomer decorated PEG-POSS particles exhibit the dynamics of a Gaussian star with an internal viscosity that rises with an increase of the host molecular weight.

Synthesis of mesoporous β-Ga2O3 nanorods using PEG as template: preparation, characterization and photocatalytic properties.

PubMed

Zhao, Weirong; Yang, Yong; Hao, Rui; Liu, Feifei; Wang, Yan; Tan, Min; Tang, Jing; Ren, Daqing; Zhao, Dongye

2011-09-15

Mesoporous wide bandgap semiconductors offer high photocatalytic oxidation and mineralization activities. In this study, mesoporous β-Ga(2)O(3) diamond nanorods with 200-300 nm in diameter and 1.0-1.2 μm in length were synthesized via a urea-based hydrothermal method using polyethylene glycol (PEG) as template agent. The UV photocatalytic oxidation activity of β-Ga(2)O(3) for gaseous toluene was evaluated, and 7 kinds of intermediates were monitored online by a proton transfer reaction mass spectrometry. Photoluminescence spectra manifested that the dosage and molecular weight of PEG are crucial for formation of vacancies and photocatalytic oxidation activities. A PEG-assisted hydrothermal formation mechanism of mesoporous β-Ga(2)O(3) diamond nanorods was proposed. Based on the health risk influence index (η) of the intermediates, the calculated health risks revealed that the β-Ga(2)O(3) nanorods with a η value of 9.6 are much safer than TiO(2) (η = 17.6). Copyright © 2011 Elsevier B.V. All rights reserved.

Ultrafiltration of pegylated proteins

NASA Astrophysics Data System (ADS)

Molek, Jessica R.

There is considerable clinical interest in the use of "second-generation" therapeutics produced by conjugation of a native protein with various polymers including polyethylene glycol (PEG). PEG--protein conjugates, so-called PEGylated proteins, can exhibit enhanced stability, half-life, and bioavailability. One of the challenges in the commercial production of PEGylated proteins is the purification required to remove unreacted polymer, native protein, and in many cases PEGylated proteins with nonoptimal degrees of conjugation. The overall objective of this thesis was to examine the use of ultrafiltration for the purification of PEGylated proteins. This included: (1) analysis of size-based separation of PEGylated proteins using conventional ultrafiltration membranes, (2) use of electrically-charged membranes to exploit differences in electrostatic interactions, and (3) examination of the effects of PEGylation on protein fouling. The experimental results were analyzed using appropriate theoretical models, with the underlying physical properties of the PEGylated proteins evaluated using size exclusion chromatography, capillary electrophoresis, dynamic light scattering, and reverse phase chromatography. PEGylated proteins were produced by covalent attachment of activated PEG to a protein via primary amines on the lysine residues. A simple model was developed for the reaction kinetics, which was used to explore the effect of reaction conditions and mode of operation on the distribution of PEGylated products. The effective size of the PEGylated proteins was evaluated using size exclusion chromatography, with appropriate correlations developed for the size in terms of the molecular weight of the native protein and attached PEG. The electrophoretic mobility of the PEGylated proteins were evaluated by capillary electrophoresis with the data in good agreement with a simple model accounting for the increase in protein size and the reduction in the number of protonated amine groups in the PEGylated proteins. Ultrafiltration experiments were performed using PEGylated alpha-lactalbumin, ovalbumin, and bovine serum albumin. In contrast to the size exclusion chromatography data, the sieving coefficient of the PEGylated proteins depended upon both the number and size of the attached PEG chains due to the elongation or deformation of the PEG associated with the filtrate flux. Sieving coefficients at low filtrate flux were in good agreement with predictions of available hydrodynamic models, with significant elongation occurring when the Deborah number for the PEG chain exceeded 0.001. The effects of electrostatic interactions on the ultrafiltration of PEGylated proteins were examined using electrically-charged membranes generated by covalent attachment of sulphonic acid groups to the base cellulosic membrane. Transmission of PEGylated proteins through charged membranes was dramatically reduced at low ionic strength due to strong electrostatic interactions, despite the presence of the neutral PEG. The experimental results were in good agreement with model calculations developed for the partitioning of charged spheres into charged cylindrical pores. The experimental and theoretical results provide the first quantitative analysis of the effects of PEGylation on transport through semipermeable ultrafiltration membranes. The results from small-scale ultrafiltration experiments were used to develop a two-stage diafiltration process to purify PEGylated alpha-lactalbumin. The first-stage used a neutral membrane to remove the unreacted protein by exploiting differences in size. The second stage used a negatively-charged membrane to remove hydrolyzed PEG, with the PEGylated product retained by strong electrostatic interactions. This process provided a purification factor greater than 1000 with respect to the unreacted protein and greater than 20-fold with respect to the PEG with an overall yield of PEGylated alpha-lactalbumin of 78%. These results provide the first demonstration of the potential of using ultrafiltration for the purification of protein-polymer conjugates.

Curcumin-Combretastatin Nanocells as Breast Cancer Cytotoxic and Antiangiogenic Agent

DTIC Science & Technology

2008-09-01

network of polyionic (e.g. polyethylenimine , polyacrylic acid, poly-L-lysine etc.) and neutral polymer chains (e.g. PEG, Pluronic/Poloxamer...devices were then mounted back to device stations placed inside a CO2 incubator. The CI was automatically monitored by the RT-CES system. The results

Nitrobenzoxadiazole-Appended Cell Membrane Modifiers for Efficient Optoporation with Noncoherent Light.

PubMed

Otake, Saya; Okuro, Kou; Bochicchio, Davide; Pavan, Giovanni M; Aida, Takuzo

2018-05-24

FL NBD-BAM PEG2k , bearing a nitrobenzoxadiazole (NBD) unit and an oleyl terminus conjugated via a poly(ethylene glycol) (PEG) spacer ( M n = 2,000), was designed to fluorescently label cell membranes by docking its hydrophobic oleyl terminus. During laser scanning microscopy in a minimal essential medium (MEM), human hepatocellular carcinoma Hep3B cells labeled with FL NBD-BAM PEG2k appeared to undergo optoporation at their plasma membrane. We confirmed this unprecedented possibility by a series of cellular uptake experiments using negatively charged and therefore membrane-impermeable quantum dots (QDs; D h = 4.7 nm). Detailed studies indicated that the photoexcited NBD unit can generate singlet oxygen ( 1 O 2 ), which oxidizes the constituent phospholipids to transiently deteriorate the cell membrane. Reference membrane modifiers FL NBD-Oleyl and FL NBD-BAM PEG8k having shorter or longer hydrophilic spacers between the NBD and oleyl units showed a little or substantially no optoporation. For understanding these results, one must consider the following contradictory factors: (1) The photosensitized 1 O 2 generation efficiently occurs only when the NBD unit is in aqueous media, and (2) the lifetime of 1 O 2 in aqueous media is very short (3.0-3.5 μs). As supported experimentally and computationally, the hydrophilic spacer length of FL NBD-BAM PEG2k is optimal for compromising these factors. Further to note, the optoporation using FL NBD-BAM PEG2k is not accompanied by cytotoxicity.

Preparative crystallization of a single chain antibody using an aqueous two-phase system.

PubMed

Huettmann, Hauke; Berkemeyer, Matthias; Buchinger, Wolfgang; Jungbauer, Alois

2014-11-01

A simultaneous crystallization and aqueous two-phase extraction of a single chain antibody was developed, demonstrating process integration. The process conditions were designed to form an aqueous two-phase system, and to favor crystallization, using sodium sulfate and PEG-2000. At sufficiently high concentrations of PEG, a second phase was generated in which the protein crystallization occurred simultaneously. The single chain antibody crystals were partitioned to the top, polyethylene glycol-rich phase. The crystal nucleation took place in the sodium sulfate-rich phase and at the phase boundary, whereas crystal growth was progressing mainly in the polyethylene glycol-rich phase. The crystals in the polyethylene glycol-rich phase grew to a size of >50 µm. Additionally, polyethylene glycol acted as an anti-solvent, thus, it influenced the crystallization yield. A phase diagram with an undersaturation zone, crystallization area, and amorphous precipitation zone was established. Only small differences in polyethylene glycol concentration caused significant shifts of the crystallization yield. An increase of the polyethylene glycol content from 2% (w/v) to 4% (w/v) increased the yield from approximately 63-87%, respectively. Our results show that crystallization in aqueous two-phase systems is an opportunity to foster process integration. © 2014 Wiley Periodicals, Inc.

X-ray computed tomography imaging of a tumor with high sensitivity using gold nanoparticles conjugated to a cancer-specific antibody via polyethylene glycol chains on their surface

NASA Astrophysics Data System (ADS)

Nakagawa, Tomohiko; Gonda, Kohsuke; Kamei, Takashi; Cong, Liman; Hamada, Yoh; Kitamura, Narufumi; Tada, Hiroshi; Ishida, Takanori; Aimiya, Takuji; Furusawa, Naoko; Nakano, Yasushi; Ohuchi, Noriaki

2016-01-01

Contrast agents are often used to enhance the contrast of X-ray computed tomography (CT) imaging of tumors to improve diagnostic accuracy. However, because the iodine-based contrast agents currently used in hospitals are of low molecular weight, the agent is rapidly excreted from the kidney or moves to extravascular tissues through the capillary vessels, depending on its concentration gradient. This leads to nonspecific enhancement of contrast images for tissues. Here, we created gold (Au) nanoparticles as a new contrast agent to specifically image tumors with CT using an enhanced permeability and retention (EPR) effect. Au has a higher X-ray absorption coefficient than does iodine. Au nanoparticles were supported with polyethylene glycol (PEG) chains on their surface to increase the blood retention and were conjugated with a cancer-specific antibody via terminal PEG chains. The developed Au nanoparticles were injected into tumor-bearing mice, and the distribution of Au was examined with CT imaging, transmission electron microscopy, and elemental analysis using inductively coupled plasma optical emission spectrometry. The results show that specific localization of the developed Au nanoparticles in the tumor is affected by a slight difference in particle size and enhanced by the conjugation of a specific antibody against the tumor.

Quantitative fabrication, performance optimization and comparison of PEG and zwitterionic polymer antifouling coatings.

PubMed

Xing, Cheng-Mei; Meng, Fan-Ning; Quan, Miao; Ding, Kai; Dang, Yuan; Gong, Yong-Kuan

2017-09-01

A versatile fabrication and performance optimization strategy of PEG and zwitterionic polymer coatings is developed on the sensor chip of surface plasma resonance (SPR) instrument. A random copolymer bearing phosphorylcholine zwitterion and active ester side chains (PMEN) and carboxylic PEG coatings with comparable thicknesses were deposited on SPR sensor chips via amidation coupling on the precoated polydopamine (PDA) intermediate layer. The PMEN coating showed much stronger resistance to bovine serum albumin (BSA) adsorption than PEG coating at very thin thickness (∼1nm). However, the BSA resistant efficacy of PEG coating could exceed that of PMEN due to stronger steric repelling effect when the thickness increased to 1.5∼3.3nm. Interestingly, both the PEG and PMEN thick coatings (≈3.6nm) showed ultralow fouling by BSA and bovine plasma fibrinogen (Fg). Moreover, changes in the PEG end group from -OH to -COOH, protein adsorption amount could increase by 10-fold. Importantly, the optimized PMEN and PEG-OH coatings were easily duplicated on other substrates due to universal adhesion of the PDA layer, showed excellent resistance to platelet, bacteria and proteins, and no significant difference in the antifouling performances was observed. These detailed results can explain the reported discrepancy in performances between PEG and zwitterionic polymer coatings by thickness. This facile and substrate-independent coating strategy may benefit the design and manufacture of advanced antifouling biomedical devices and long circulating nanocarriers. Prevention of biofouling is one of the biggest challenges for all biomedical applications. However, it is very difficult to fabricate a highly hydrophilic antifouling coating on inert materials or large devices. In this study, PEG and zwitterion polymers, the most widely investigated polymers with best antifouling performance, are conveniently immobilized on different kinds of substrates from their aqueous solutions by precoating a polydopamine intermediate layer as the universal adhesive and readily re-modifiable surface. Importantly, the coating fabrication and antifouling performance can be monitored and optimized quantitatively by a surface plasma resonance (SPR) system. More significantly, the SPR on-line optimized coatings were successfully duplicated off-line on other substrates, and supported by their excellent antifouling properties. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Decreased prothrombotic effects of pegylated recombinant human megakaryocyte growth and development factor in thrombocytopenic state in a rat thrombosis model.

PubMed

Nishiyama, U; Kuwaki, T; Akahori, H; Kato, T; Ikeda, Y; Miyazaki, H

2005-02-01

Previous in vitro studies demonstrated that thrombopoietin (TPO) acts on platelets to activate a variety of intracellular signaling pathways and to enhance platelet sensitivity to multiple agonists. Little is known, however, about whether TPO exerts prothrombotic effects in vivo. The aim of this study was to examine the effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), a pegylated N-terminal domain of human TPO, in a rat model of venous thrombosis. A microthrombus was photochemically induced on the vessel wall of a mesenteric venule, but the vessel was not occluded by it. A single intravenous injection of PEG-rHuMGDF (3 microg kg(-1)) after the thrombus generation into normal rats enhanced the thrombus size, resulting in transient thrombotic occlusion in the majority of rats. Stimulatory effects on thrombus growth were also observed following administration of glycosylated recombinant human full-length TPO (6 microg kg(-1)). In rats rendered thrombocytopenic by total body irradiation, however, PEG-rHuMGDF, even at 300 microg kg(-1), did not induce a significant increase in thrombus size or thrombotic occlusion. Platelets from thrombocytopenic rats had decreased surface levels of c-Mpl and decreased sensitivity to PEG-rHuMGDF in an in vitro aggregation response. Thus, decreased prothrombotic effects of PEG-rHuMGDF in thrombocytopenic rats might be the result not only of low platelet counts but also of decreased platelet reactivity to PEG-rHuMGDF. These results indicate that PEG-rHuMGDF has little effect on venous thrombus formation in thrombocytopenic states associated with high endogenous TPO levels.

Anti-EGFR Peptide-Conjugated Triangular Gold Nanoplates for Computed Tomography/Photoacoustic Imaging-Guided Photothermal Therapy of Non-Small Cell Lung Cancer.

PubMed

Zhao, Ying; Liu, Wenfei; Tian, Ying; Yang, Zhenlu; Wang, Xiaofen; Zhang, Yunlei; Tang, Yuxia; Zhao, Shuang; Wang, Chunyan; Liu, Ying; Sun, Jing; Teng, Zhaogang; Wang, Shouju; Lu, Guangming

2018-05-23

Non-small cell lung cancer (NSCLC) is difficult to cure because of the high recurrence rate and the side effects of current treatments. It is urgent to develop a new treatment that is safer and more effective than current treatments against NSCLC. Herein, we constructed anti-epidermal growth factor receptor (EGFR) peptide-conjugated PEGylated triangular gold nanoplates (TGN-PEG-P75) as a targeting photothermal therapy (PTT) agent to treat NSCLC under the guidance of computed tomography (CT) and photoacoustic (PA) imaging. The surface of TGNs is successfully conjugated with a novel peptide P75 that has the specific affinity to epidermal growth factor receptor (EGFR). It is found that the EGFR is overexpressed in NSCLC cells. The TGN-PEG-P75 has uniform edge length (77.9 ± 7.0 nm) and neutrally charged surface. The cell uptake experiments demonstrate remarkable affinity of the TGN-PEG-P75 to high EGFR expression cells than low EGFR expression cells (5.1-fold). Thanks to the strong near-infrared absorbance, high photothermal conversion efficiency, and the increased accumulation in tumor cells via the interaction of P75 and EGFR, TGN-PEG-P75 exhibits 3.8-fold superior therapeutic efficacy on HCC827 cells than TGN-PEG. The in vivo CT/PA dual-modal imaging of the TGN-PEG-P75 is helpful in selecting the optimal treatment time and providing real-time visual guidance of PTT. Furthermore, treatments on HCC827 tumor-bearing mouse model demonstrate that the growth of NSCLC cells can be effectively inhibited by the TGN-PEG-P75 through PTT, indicating the great promise of the nanoplatform for treating NSCLC in vivo.

Refolding of laccase from Trametes versicolor using aqueous two phase systems: Effect of different additives.

PubMed

Sánchez-Trasviña, Calef; Mayolo-Deloisa, Karla; González-Valdez, José; Rito-Palomares, Marco

2017-07-21

Protein refolding is a strategy used to obtain active forms of proteins from inclusion bodies. On its part, laccase is an enzyme with potential for different biotechnological applications but there are few reports regarding its refolding which in many cases is considered inefficient due to the poor obtained refolding yields. Aqueous Two-Phase Systems (ATPS) have been used for the refolding of proteins getting acceptable recovery percentages since PEG presents capacity to avoid protein aggregation. In this work, 48 PEG-phosphate ATPS were analyzed to study the impact of different parameters (i.e. tie line length (TLL), volume ratio (V R ) and PEG molecular weight) upon the recovery and refolding of laccase. Additionally, since laccase is a metalloprotein, the use of additives (individually and in mixture) was studied with the aim of favoring refolding. Results showed that laccase presents a high affinity for the PEG-rich phase obtaining recovery values of up to 90%. Such affinity increases with increasing TLL and decreases when PEG molecular weight and V R increase. In denatured state, this PEG-rich phase affinity decreases drastically. However, the use of additives such as l-cysteine, glutathione oxidized, cysteamine and Cu +2 was critical in improving refolding yield values up to 100%. The best conditions for the refolding of laccase were obtained using the PEG 400gmol -1 , TLL 45% w/w, V R 3 ATPS and a mixture of 2.5mM cysteamine with 1mM Cu +2 . To our knowledge, this is the first time that the use of additives and the behavior of the mixture of such additives to enhance refolding performance in ATPS is reported. Copyright © 2017 Elsevier B.V. All rights reserved.

Germinaton performance of selected local soybean (Glycine max (L.) Merrills) cultivars during drought stress induced by Polyethylene Glycol (PEG)

NASA Astrophysics Data System (ADS)

Pane, R. F.; Damanik, R. I.; Khardinata, E. H.

2018-02-01

Drought stress is one of the factors that can decreased growth and production, so that required a variety that has the ability to sustain cellular metabolism, and growth during the stress. This research was aimed to investigated the involvement of germination performance invitro of five local soybean cultivars, Grobogan, Kaba, Anjasmoro, Argomulyo, and Dering to drought stress induced by polyethylene glycol (PEG) 6000 (0%, 2%, 4%, and 6%). The measurable seedling traits as the day appearance of shoots and roots, total of leaves, shoot length, root length, fresh plant weight, dry plant weight, fresh root weight, and dry root weight under control as well as water stress condition were recorded. The experiment units were arranged in factorial completely randomized design with four replications. The result showed that the value for most parameters was recorded highest for Argomulyo cultivar compared with Dering cultivar which is known to be tolerant to drought. In terms of roots performance, Grobogan and Argomulyo cultivars produced the longest and heaviest of roots, while Grobogan cultivar had no significant different for root length compared with control. In conclusion, the root length and fresh weight root parameters can be used as quick criteria for drought tolerance.

Flexible polyimides through one-pot synthesis as water-soluble binders for silicon anodes in lithium ion batteries

NASA Astrophysics Data System (ADS)

Yao, Dahua; Yang, Yu; Deng, Yonghong; Wang, Chaoyang

2018-03-01

A series of polyimides, which contain polyethylene glycol (PEG) segments with different molecular weight in the polymer chains, are synthesized through a facile one-pot method and characterized by Fourier transform infrared spectroscopy and hydrogen nuclear magnetic resonance spectroscopy. The main part of polyimides is originated from trimellitic anhydride chloride (TMAC) and 4,4‧-methylenedianiline, onto which PEG segments are introduced through an esterification reaction with TMAC. These obtained polyimides, which acquire excellent water solubility after being neutralized by triethylamine, are applied as water-soluble binders to silicon negative electrodes for lithium ion batteries, and significantly improve the electrochemical performance of silicon anodes. Specially, the PI-200 (polyimide copolymerized with PEG-200) based silicon electrode exhibits a high initial discharge capacity of 2989.7 mAh g-1 and remains about 2235.5 mAh g-1 after 200 cycles at the current density of 0.1 C (420 mA g-1).

Solid phase pegylation of hemoglobin.

PubMed

Suo, Xiaoyan; Zheng, Chunyang; Yu, Pengzhan; Lu, Xiuling; Ma, Guanghui; Su, Zhiguo

2009-01-01

A solid phase conjugation process was developed for attachment of polyethylene glycol to hemoglobin molecule. Bovine hemoglobin was loaded onto an ion exchange chromatography column and adsorbed by the solid medium. Succinimidyl carbonate mPEG was introduced in the mobile phase after the adsorption. Pegylation took place between the hemoglobin on the solid phase, and the pegylation reagent in the liquid phase. A further elution was carried out to separate the pegylated and the unpegylated protein. Analysis by HPSEC, SDS-PAGE, and MALLS demonstrated that the fractions eluted from the solid phase contained well-defined components. Pegylated hemoglobin with one PEG chain was obtained with the yield of 75%, in comparison to the yield of 30% in the liquid phase pegylation. The P(50) values of the mono-pegylated hemoglobin, prepared with SC-mPEG 5 kDa, 10 kDa and 20 kDa, were 19.97, 20.23 and 20.54 mmHg, which were much closer to the value of red blood cells than that of pegylated hemoglobin prepared with the conventional method.

Purification and crystallization of Bacillus subtilis NrnA, a novel enzyme involved in nanoRNA degradation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nelersa, Claudiu M.; Schmier, Brad J.; Malhotra, Arun

2012-05-08

The final step in RNA degradation is the hydrolysis of RNA fragments five nucleotides or less in length (nanoRNA) to mononucleotides. In Escherichia coli this step is carried out by oligoribonuclease (Orn), a DEDD-family exoribonuclease that is conserved throughout eukaryotes. However, many bacteria lack Orn homologs, and an unrelated DHH-family phosphoesterase, NrnA, has recently been identified as one of the enzymes responsible for nanoRNA degradation in Bacillus subtilis. To understand its mechanism of action, B. subtilis NrnA was purified and crystallized at room temperature using the hanging-drop vapor-diffusion method with PEG 4000, PEG 3350 or PEG MME 2000 as precipitant.more » The crystals belonged to the primitive monoclinic space group P2{sub 1}, with unit-cell parameters a = 50.62, b = 121.3, c = 123.4 {angstrom}, {alpha} = 90, {beta} = 91.31, {gamma} = 90{sup o}.« less

Final report on the safety assessment of Triethylene Glycol and PEG-4.

PubMed

2006-01-01

Triethylene Glycol and PEG-4 (polyethylene glycol) are polymers of ethylene oxide alcohol. Triethylene Glycol is a specific three-unit chain, whereas PEG-4 is a polymer with an average of four units, but may contain polymers ranging from two to eight ethylene oxide units. In the same manner, other PEG compounds, e.g., PEG-6, are mixtures and likely contain some Triethylene Glycol and PEG-4. Triethylene Glycol is a fragrance ingredient and viscosity decreasing agent in cosmetic formulations, with a maximum concentration of use of 0.08% in skin-cleansing products. Following oral doses, Triethylene Glycol and its metabolites are excreted primarily in urine, with small amounts released in feces and expired air. With oral LD50 values in rodents from 15 to 22 g/kg, this compound has little acute toxicity. Rats given short term oral doses of 3% in water showed no signs of toxicity, whereas all rats given 10% died by the 12th day of exposure. At levels up to 1 g/m3, rats exposed to aerosolized Triethylene Glycol for 6 h per day for 9 days showed no signs of toxicity. Rats fed a diet containing 4% Triethylene Glycol for 2 years showed no signs of toxicity. There were no treatment-related effects on rats exposed to supersaturated Triethylene Glycol vapor for 13 months nor in rats that consumed 0.533 cc Triethylene Glycol per day in drinking water for 13 months. Triethylene Glycol was not irritating to the skin of rabbits and produced only minimal injury to the eye. In reproductive and developmental toxicity studies in rats and mice, Triethylene Glycol did not produce biologically significant embryotoxicity or teratogenicity. However, some maternal toxicity was seen in dams given 10 ml/kg/day during gestation. Triethylene Glycol was not mutagenic or genotoxic in Ames-type assays, the Chinese hamster ovary mutation assay, and the sister chromatid exchange assays. PEG-4 is a humectant and solvent in cosmetic products, with a maximum concentration of use of 20% in the "other manicuring preparations" product category. This ingredient, with an oral LD50 in rats of 32.77 g/kg, has low acute toxicity. Rats given up to 50,000 ppm PEG-4 in drinking water for 5 days showed no permanent signs of toxicity. Rats given daily oral doses up to 2 g/kg/day of PEG-4 for 33 days showed no signs of toxicity. Undiluted PEG-4 produced only minimal injury to the rabbit eye. PEG-4 was not mutagenic in Ames-type assays, did not induce chromosome aberration in an in vivo bone marrow assay, and was negative for genotoxicity in a dominant lethal assay using rats. Other PEG compounds, which have previously been reviewed by the Cosmetic Ingredient Review (CIR) Expert Panel, e.g., PEG-6, are mixtures that likely include Triethylene Glycol and PEG-4, so these data were also considered. PEG-6 and PEG-8 were not dermal irritants in several rabbit studies. PEG-2 Stearate had a potential for slight irritation in rabbits but was not a sensitizer in guinea pigs. PEG-2 Cocamine was a moderate irritant in rabbits, producing severe erythema. In one dermal study, PEG-2 Cocamine was determined to be corrosive to rabbit skin, causing eschar and necrosis. PEG-6 and PEG-8 caused little to no ocular irritation. PEG-8 was not mutagenic or genotoxic in a Chinese hamster ovary assay, a sister-chromatid exchange assay, and in an unscheduled DNA synthesis assay. In clinical studies on normal skin, PEG-6 and PEG-8 caused mild cases of immediate hypersensitivity; PEG-8 was not a sensitizer; PEG-2 Stearate was not an irritant, a sensitizer, or a photosensitizer; and PEG-6 Stearate was not an irritant or sensitizer. In damaged skin, cases of systemic toxicity and contact dermatitis in burn patients were attributed to a PEG-based topical ointment. The CIR Expert Panel acknowledged the lack of dermal sensitization data for Triethylene Glycol and dermal irritation and sensitization data for PEG-4. That PEG-6, PEG-8, and PEG-2 Stearate were not irritants or sensitizers suggested that Triethylene Glycol and PEG-4 also would not be irritants or sensitizers, and the absence of any reported reactions in the case literature and the professional experience of the Expert Panel further supported the absence of any significant sensitization potential. The need for additional data to demonstrate the safety of PEGs Cocamine was related to the Cocamine moiety and is not relevant here. The Panel reminded formulators of cosmetic products that, as with other PEG compounds, Triethylene Glycol and PEG-4 should not be used on damaged skin because of cases of systemic toxicity and contact dermatitis in burn patients have been attributed to a PEG-based topical ointment. Based on its consideration of the available information, the CIR Expert Panel concluded that Triethylene Glycol and PEG-4 are safe as cosmetic ingredients in the present practices and concentrations of use as described in this safety assessment.

Dependence of Ion Dynamics on the Polymer Chain Length in Poly(ethylene oxide)-Based Polymer Electrolytes.

PubMed

Chattoraj, Joyjit; Knappe, Marisa; Heuer, Andreas

2015-06-04

It is known from experiments that in the polymer electrolyte system, which contains poly(ethylene oxide) chains (PEO), lithium-cations (Li(+)), and bis(trifluoromethanesulfonyl)imide-anions (TFSI(-)), the cation and the anion diffusion and the ionic conductivity exhibit a similar chain-length dependence: with increasing chain length, they start dropping steadily, and later, they saturate to constant values. These results are surprising because Li-cations are strongly correlated with the polymer chains, whereas TFSI-anions do not have such bonding. To understand this phenomenon, we perform molecular dynamics simulations of this system for four different polymer chain lengths. The diffusion results obtained from our simulations display excellent agreement with the experimental data. The cation transport model based on the Rouse dynamics can successfully quantify the Li-diffusion results, which correlates Li diffusion with the polymer center-of-mass motion and the polymer segmental motion. The ionic conductivity as a function of the chain length is then estimated based on the chain-length-dependent ion diffusion, which shows a temperature-dependent deviation for short chain lengths. We argue that in the first regime, counterion correlations modify the conductivity, whereas for the long chains, the system behaves as a strong electrolyte.

Hydrophilization of Magnetic Nanoparticles with Modified Alternating Copolymers. Part 1: The Influence of the Grafting

PubMed Central

Bronstein, Lyudmila M.; Shtykova, Eleonora V.; Malyutin, Andrey; Dyke, Jason C.; Gunn, Emily; Gao, Xinfeng; Stein, Barry; Konarev, Peter V.; Dragnea, Bogdan; Svergun, Dmitri I.

2010-01-01

Iron oxide nanoparticles (NPs) with a diameter 21.6 nm were coated with poly(maleic acid-alt-1-octadecene) (PMAcOD) modified with grafted 5,000 Da poly(ethyelene glycol) (PEG) or short ethylene glycol (EG) tails. The coating procedure utilizes hydrophobic interactions of octadecene and oleic acid tails, while the hydrolysis of maleic anhydride moieties as well as the presence of hydrophilic PEG (EG) tails allows the NP hydrophilicity. The success of the NP coating was found to be independent of the degree of grafting which was varied between 20 and 80% of the –MacOD-units, but depended on the length of the grafted tail. The NP coating and hydrophilization did not occur when the modified copolymer contained 750 Da PEG tails independently of the grafting degree. To explain this phenomenon the micellization of the modified PMAcOD copolymers in water was analyzed by small angle x-ray scattering (SAXS). The PMAcOD molecules with the grafted 750 Da PEG tails form compact non-interacting disk-like micelles, whose stability apparently allows for no interactions with the NP hydrophobic shells. The PMAcOD containing the 5,000 Da PEG and EG tails form much larger aggregates capable of an efficient coating of the NPs. The coated NPs were characterized using transmission electron microscopy, dynamic light scattering, ζ-potential measurements, and thermal gravimetry analysis. The latter method demonstrated that the presence of long PEG tails in modified PMAcOD allows the attachment of fewer macromolecules (by a factor of ~20) compared to the case of non-modified or EG modified PMAcOD, emphasizing the importance of PEG tails in NP hydrophilization. The NPs coated with PMAcOD modified with 60% (towards all –MAcOD- units) of the 5,000 PEG tails bear a significant negative charge and display good stability in buffers. Such NPs can be useful as magnetic cores for virus-like particle formation. PMID:21221425

Functional PEG-PAMAM-tetraphosphonate capped NaLnF₄ nanoparticles and their colloidal stability in phosphate buffer.

PubMed

Zhao, Guangyao; Tong, Lemuel; Cao, Pengpeng; Nitz, Mark; Winnik, Mitchell A

2014-06-17

Developing surface coatings for NaLnF4 nanoparticles (NPs) that provide long-term stability in solutions containing competitive ions such as phosphate remains challenging. An amine-functional polyamidoamine tetraphosphonate (NH2-PAMAM-4P) as a multidentate ligand for these NPs has been synthesized and characterized as a ligand for the surface of NaGdF4 and NaTbF4 nanoparticles. A two-step ligand exchange protocol was developed for introduction of the NH2-PAMAM-4P ligand on oleate-capped NaLnF4 NPs. The NPs were first treated with methoxy-poly(ethylene glycol)-monophosphoric acid (M(n) = 750) in tetrahydrofuran. The mPEG750-OPO3-capped NPs were stable colloidal solutions in water, where they could be ligand-exchanged with NH2-PAMAM-4P. The surface amine groups on the NPs were available for derivatization to attach methoxy-PEG (M(n) = 2000) and biotin-terminated PEG (M(n) = 2000) chains. The surface coverage of ligands on the NPs was examined by thermal gravimetric analysis, and by a HABA analysis for biotin-containing NPs. Colloidal stability of the NPs was examined by dynamic light scattering. NaGdF4 and NaTbF4 NPs capped with mPEG2000-PAMAM-4P showed colloidal stability in DI water and in phosphate buffer (10 mM, pH 7.4). A direct comparison with NaTbF4 NPs capped with a mPEG2000-lysine-based tetradentate ligand that we reported previously (Langmuir 2012, 28, 12861-12870) showed that both ligands provided long-term stability in phosphate buffer, but that the lysine-based ligand provided better stability in phosphate-buffered saline.

Biomolecular strategies for cell surface engineering

NASA Astrophysics Data System (ADS)

Wilson, John Tanner

Islet transplantation has emerged as a promising cell-based therapy for the treatment of diabetes, but its clinical efficacy remains limited by deleterious host responses that underlie islet destruction. In this dissertation, we describe the assembly of ultrathin conformal coatings that confer molecular-level control over the composition and biophysicochemical properties of the islet surface with implications for improving islet engraftment. Significantly, this work provides novel biomolecular strategies for cell surface engineering with broad biomedical and biotechnological applications in cell-based therapeutics and beyond. Encapsulation of cells and tissue offers a rational approach for attenuating deleterious host responses towards transplanted cells, but a need exists to develop cell encapsulation strategies that minimize transplant volume. Towards this end, we endeavored to generate nanothin films of diverse architecture with tunable properties on the extracellular surface of individual pancreatic islets through a process of layer-by-layer (LbL) self assembly. We first describe the formation of poly(ethylene glycol) (PEG)-rich conformal coatings on islets via LbL self assembly of poly(L-lysine)-g-PEG(biotin) and streptavidin. Multilayer thin films conformed to the geometrically and chemically heterogeneous islet surface, and could be assembled without loss of islet viability or function. Significantly, coated islets performed comparably to untreated controls in a murine model of allogenic intraportal islet transplantation, and, to our knowledge, this is the first study to report in vivo survival and function of nanoencapsulated cells or cell aggregates. Based on these findings, we next postulated that structurally similar PLL-g-PEG copolymers comprised of shorter PEG grafts might be used to initiate and propagate the assembly of polyelectrolyte multilayer (PEM) films on pancreatic islets, while simultaneously preserving islet viability. Through control of PLL backbone molecular weight, PEG chain length, and grafting ratio, PLL-g-PEG copolymers were rendered cytocompatible and used to initiate and propagate the growth of cell surface-supported PEM films. Planar characterization of this novel class of PEM films indicated that film thickness and composition may be tailored through appropriate control of layer number and copolymer properties. Furthermore, these investigations have helped establish a conceptual framework for the rational design of cell surface-supported thin films, with the objective of translating the diverse biomedical and biotechnological applications of PEM films to cellular interfaces. Important to the development of effective conformal islet coatings is an inherent strategy through which to incorporate bioactive molecules for directing desired biochemical or cellular responses. Towards this end, PLL-g-PEG copolymers functionalized with biotin, azide, and hydrazide moieties were synthesized and used, either alone or in combination, to capture streptavidin-, triphenylphosphine-, and aldehyde-labeled probes, respectively, on the islet surface. Additionally, PEM films assembled using alginate chemically modified to contain aldehyde groups could be used to introduce hydrazide-functionalized molecules to the islet surface. Hence, modified film constituents may be used as modular elements for controlling the chemical composition cell and tissue surfaces. Finally, we report a strategy for tethering thrombomodulin (TM) to the islet surface. Through site-specific, C-terminal biotinylation of TM and optimization of cell surface biotinylation, TM could be integrated with the islet surface. Re-engineering of islet surfaces with TM resulted in an increased catalytic capacity of islets to generate the powerful anti-inflammatory agent, activated protein C (APC), thereby providing a facile strategy for increasing the local concentration of APC at the site of transplantation.

A Soil-Plate Based Pipeline for Assessing Cereal Root Growth in Response to Polyethylene Glycol (PEG)-Induced Water Deficit Stress

PubMed Central

Nelson, Sven K.; Oliver, Melvin J.

2017-01-01

Drought is a serious problem that causes losses in crop-yield every year, but the mechanisms underlying how roots respond to water deficit are difficult to study under controlled conditions. Methods for assaying root elongation and architecture, especially for seedlings, are commonly achieved on artificial media, such as agar, moistened filter paper, or in hydroponic systems. However, it has been demonstrated that measuring root characteristics under such conditions does not accurately mimic what is observed when plants are grown in soil. Morphological changes in root behavior occur because of differences in solute diffusion, mechanical impedance, exposure to light (in some designs), and gas exchange of roots grown under these conditions. To address such deficiencies, we developed a quantitative method for assaying seedling root lengths and germination in soil using a plate-based approach with wheat as a model crop. We also further developed the method to include defined water deficits stress levels using the osmotic properties of polyethylene glycol (PEG). Seeds were sown into soil-filled vertical plates and grown in the dark. Root length measurements were collected using digital photography through the transparent lid under green lighting to avoid effects of white light exposure on growth. Photographs were analyzed using the cross-platform ImageJ plugin, SmartRoot, which can detect root edges and partially automate root detection for extraction of lengths. This allowed for quick measurements and straightforward and accurate assessments of non-linear roots. Other measurements, such as root width or angle, can also be collected by this method. An R function was developed to collect exported root length data, process and reformat the data, and output plots depicting root/shoot growth dynamics. For water deficit experiments, seedlings were transplanted side-by-side into well-watered plates and plates containing PEG solutions to simulate precise water deficits. PMID:28785272

A Soil-Plate Based Pipeline for Assessing Cereal Root Growth in Response to Polyethylene Glycol (PEG)-Induced Water Deficit Stress.

PubMed

Nelson, Sven K; Oliver, Melvin J

2017-01-01

Drought is a serious problem that causes losses in crop-yield every year, but the mechanisms underlying how roots respond to water deficit are difficult to study under controlled conditions. Methods for assaying root elongation and architecture, especially for seedlings, are commonly achieved on artificial media, such as agar, moistened filter paper, or in hydroponic systems. However, it has been demonstrated that measuring root characteristics under such conditions does not accurately mimic what is observed when plants are grown in soil. Morphological changes in root behavior occur because of differences in solute diffusion, mechanical impedance, exposure to light (in some designs), and gas exchange of roots grown under these conditions. To address such deficiencies, we developed a quantitative method for assaying seedling root lengths and germination in soil using a plate-based approach with wheat as a model crop. We also further developed the method to include defined water deficits stress levels using the osmotic properties of polyethylene glycol (PEG). Seeds were sown into soil-filled vertical plates and grown in the dark. Root length measurements were collected using digital photography through the transparent lid under green lighting to avoid effects of white light exposure on growth. Photographs were analyzed using the cross-platform ImageJ plugin, SmartRoot, which can detect root edges and partially automate root detection for extraction of lengths. This allowed for quick measurements and straightforward and accurate assessments of non-linear roots. Other measurements, such as root width or angle, can also be collected by this method. An R function was developed to collect exported root length data, process and reformat the data, and output plots depicting root/shoot growth dynamics. For water deficit experiments, seedlings were transplanted side-by-side into well-watered plates and plates containing PEG solutions to simulate precise water deficits.

Uptake and intracellular processing of PEG-liposomes and PEG-immunoliposomes by kupffer cells in vitro 1 *.

PubMed

Koning, G A; Morselt, H W; Kamps, J A; Scherphof, G L

2001-01-01

Specific targeting of drugs to for instance tumors or sites of inflammation may be achieved by means of immunoliposomes carrying site-specific antibodies on their surface. The presence of these antibodies may adversely affect the circulation kinetics of such liposomes as a result of interactions with cells of the mononuclear phagocyte system (MPS), mainly represented by macrophages in liver and spleen. The additional insertion of poly(ethylene glycol) chains on the surface of the immunoliposomes may, however, attenuate this effect. We investigated the influence of surface-coupled rat or rabbit antibodies and of PEG on the uptake of liposomes by rat Kupffer cells in culture with (3)H-cholesteryloleyl ether as a metabolically stable marker. Additionally, we assessed the effects of surface-bound IgG and PEG on the intracellular processing of the liposomes by the Kupffer cells, based on a double-label assay using the (3)H-cholesteryl ether as an absolute measure for liposome uptake and the hydrolysis of the degradable marker cholesteryl-(14)C-oleate as relative measure of degradation. Attachment of both rat and rabbit antibodies to PEG-free liposomes caused a several-fold increase in apparent size. The uptake by Kupffer cells, however, was 3-4 fold higher for the rat than for the rabbit IgG liposomes. The presence of PEG drastically reduced the difference between these liposome types. Uptake of liposomes without antibodies amounted to only about 10% (non-PEGylated) or less (PEGylated) of that of the immunoliposomes. In contrast to the marked effects of IgG and PEG on Kupffer cell uptake, the rate of intracellular processing of the liposomes remained virtually unaffected by the presence of these substances on the liposomal surface. These observations are discussed with respect to the design of optimally formulated liposomal drug preparations, combining maximal therapeutic efficacy with minimal toxicity.

Cellular uptake and trafficking of polydiacetylene micelles

NASA Astrophysics Data System (ADS)

Gravel, Edmond; Thézé, Benoit; Jacques, Isabelle; Anilkumar, Parambath; Gombert, Karine; Ducongé, Frédéric; Doris, Eric

2013-02-01

Polydiacetylene (PDA) micelles coated with either carboxylate-, ammonium-, or methoxy-polyethyleneglycol (PEG) chains were assembled and loaded with a fluorescent dye (DiO). Their interaction with MCF-7 human breast tumor cells was investigated by epi-fluorescence microscopy and fluorescence-activated cell sorting (FACS) to determine their internalization pathway and intracellular fate. It was found that the ionic character of the micelles influenced their internalization kinetics through a caveolae-mediated pathway and that all micelle types behaved somewhat similarly inside cells.Polydiacetylene (PDA) micelles coated with either carboxylate-, ammonium-, or methoxy-polyethyleneglycol (PEG) chains were assembled and loaded with a fluorescent dye (DiO). Their interaction with MCF-7 human breast tumor cells was investigated by epi-fluorescence microscopy and fluorescence-activated cell sorting (FACS) to determine their internalization pathway and intracellular fate. It was found that the ionic character of the micelles influenced their internalization kinetics through a caveolae-mediated pathway and that all micelle types behaved somewhat similarly inside cells. Electronic supplementary information (ESI) available: Detailed synthetic procedures and supplementary figures. See DOI: 10.1039/c2nr34149b

Singular eigenstates in the even(odd) length Heisenberg spin chain

NASA Astrophysics Data System (ADS)

Ranjan Giri, Pulak; Deguchi, Tetsuo

2015-05-01

We study the implications of the regularization for the singular solutions on the even(odd) length spin-1/2 XXX chains in some specific down-spin sectors. In particular, the analytic expressions of the Bethe eigenstates for three down-spin sector have been obtained along with their numerical forms in some fixed length chains. For an even-length chain if the singular solutions \\{{{λ }α }\\} are invariant under the sign changes of their rapidities \\{{{λ }α }\\}=\\{-{{λ }α }\\}, then the Bethe ansatz equations are reduced to a system of (M-2)/2((M-3)/2) equations in an even (odd) down-spin sector. For an odd N length chain in the three down-spin sector, it has been analytically shown that there exist singular solutions in any finite length of the spin chain of the form N=3(2k+1) with k=1,2,3,\\cdots . It is also shown that there exist no singular solutions in the four down-spin sector for some odd-length spin-1/2 XXX chains.

Synthesis, characterization, and application of reversible PDLLA-PEG-PDLLA copolymer thermogels in vitro and in vivo

PubMed Central

Shi, Kun; Wang, Ya-Li; Qu, Ying; Liao, Jin-Feng; Chu, Bing-Yang; Zhang, Hua-Ping; Luo, Feng; Qian, Zhi-Yong

2016-01-01

In this study, a series of injectable thermoreversible and thermogelling PDLLA-PEG-PDLLA copolymers were developed and a systematic evaluation of the thermogelling system both in vitro and in vivo was performed. The aqueous PDLLA-PEG-PDLLA solutions above a critical gel concentration could transform into hydrogel spontaneously within 2 minutes around the body temperature in vitro or in vivo. Modulating the molecular weight, block length and polymer concentration could adjust the sol-gel transition behavior and the mechanical properties of the hydrogels. The gelation was thermally reversible due to the physical interaction of copolymer micelles and no crystallization formed during the gelation. Little cytotoxicity and hemolysis of this polymer was found, and the inflammatory response after injecting the hydrogel to small-animal was acceptable. In vitro and in vivo degradation experiments illustrated that the physical hydrogel could retain its integrity as long as several weeks and eventually be degraded by hydrolysis. A rat model of sidewall defect-bowel abrasion was employed, and a significant reduction of post-operative adhesion has been found in the group of PDLLA-PEG-PDLLA hydrogel-treated, compared with untreated control group and commercial hyaluronic acid (HA) anti-adhesion hydrogel group. As such, this PDLLA-PEG-PDLLA hydrogel might be a promising candidate of injectable biomaterial for medical applications. PMID:26752008

Biocompatible Polymeric Nanoparticles as Promising Candidates for Drug Delivery.

PubMed

Łukasiewicz, Sylwia; Szczepanowicz, Krzysztof; Błasiak, Ewa; Dziedzicka-Wasylewska, Marta

2015-06-16

The use of polymeric nanoparticles (NPs) in pharmacology provides many benefits because this approach can increase the efficacy and selectivity of active compounds. However, development of new nanocarriers requires better understanding of the interactions between NPs and the immune system, allowing for the optimization of NP properties for effective drug delivery. Therefore, in the present study, we focused on the investigation of the interactions between biocompatible polymeric NPs and a murine macrophage cell line (RAW 264.7) and a human monocytic leukemia cell line (THP-1). NPs based on a liquid core with polyelectrolyte shells were prepared by sequential adsorption of polyelectrolytes (LbL) using AOT (docusate sodium salt) as the emulsifier and the biocompatible polyelectrolytes polyanion PGA (poly-l-glutamic acid sodium salt) and polycation PLL (poly l-lysine). The average size of the obtained NPs was 80 nm. Pegylated external layers were prepared using PGA-g-PEG (PGA grafted by PEG poly(ethylene glycol)). The influence of the physicochemical properties of the NPs (charge, size, surface modification) on viability, phagocytosis potential, and endocytosis was studied. Internalization of NPs was determined by flow cytometry and confocal microscopy. Moreover, we evaluated whether addition of PEG chains downregulates particle uptake by phagocytic cells. The presented results confirm that the obtained PEG-grafted NPs are promising candidates for drug delivery.

Mesoporous silica nanoparticle-based intelligent drug delivery system for bienzyme-responsive tumour targeting and controlled release.

PubMed

Zhang, Yang; Xu, Juan

2018-01-01

This paper proposes a novel type of multifunctional envelope-type mesoporous silica nanoparticle (MSN) to achieve cancer cell targeting and drug-controlled release. In this system, MSNs were first modified by active targeting moiety hyaluronic acid (HA) for breast cancer cell targeting and hyaluronidases (Hyal)-induced intracellular drug release. Then gelatin, a proteinaceous biopolymer, was grafted onto the MSNs to form a capping layer via glutaraldehyde-mediated cross-linking. To shield against unspecific uptake of cells and prolong circulation time, the nanoparticles were further decorated with poly(ethylene glycol) polymers (PEG) to obtain MSN@HA-gelatin-PEG (MHGP). Doxorubicin (DOX), as a model drug, was loaded into PEMSN to assess the breast cancer cell targeting and drug release behaviours. In vitro study revealed that PEG chains protect the targeting ligand and shield against normal cells. After reaching the breast cancer cells, MMP-2 overpressed by cells hydrolyses gelatin layer to deshield PEG and switch on the function of HA. As a result, DOX-loaded MHGP was selectively trapped by cancer cells through HA receptor-mediated endocytosis and subsequently release DOX due to Hyal-catalysed degradation of HA. This system presents successful bienzyme-responsive targeting drug delivery in an optimal fashion and provides potential applications for targeted cancer therapy.

Efficient Intracellular siRNA Delivery by Ethyleneimine-Modified Amphiphilic Macromolecules

PubMed Central

Sparks, Sarah M.; Waite, Carolyn L.; Harmon, Alexander M.; Nusblat, Leora M.; Roth, Charles M.; Uhrich, Kathryn E.

2013-01-01

Summary New materials that can bind and deliver oligonucleotides such as short interfering RNA (siRNA) without toxicity are greatly needed to fulfill the promise of therapeutic gene silencing. Amphiphilic macromolecules (AMs) were functionalized with linear ethyleneimines to create cationic AMs capable of complexing with siRNA. Structurally, the parent AM is formed from a mucic acid backbone whose tetra-hydroxy groups are alkylated with 12-carbon aliphatic chains to form the hydrophobic component of the macromolecule. This alkylated mucic acid is then mono-functionalized with poly(ethylene glycol) (PEG) as a hydrophilic component. The resulting AM contains a free carboxylic acid within the hydrophobic domain. In this work, linear ethyleneimines were conjugated to the free carboxylic acid to produce an AM with one primary amine (1N) or one primary amine and four secondary amines (5N). Further, an AM with amine substitution both to the free carboxylic acid in the hydrophobic domain and also to the adjacent PEG was synthesized to produce a polymer with one primary amine and eight secondary amines (9N), four located on each side of the AM hydrophobic domain. All amine-functionalized AMs formed nanoscale micelles but only the 5N and 9N AMs had cationic zeta potentials, which increased with increasing number of amines. All AMs exhibited less inherent cytotoxicity than linear polyethyleneimine (L-PEI) at concentrations of 10 µM and above. By increasing the length of the cationic ethyleneimine chain and the total number of amines, successful siRNA complexation and cellular siRNA delivery was achieved in a malignant glioma cell line. In addition, siRNA-induced silencing of firefly luciferase was observed using complexes of siRNA with the 9N AM and comparable to L-PEI, yet showed better cell viability at higher concentrations (above 10 µM). This work highlights the promise of cationic AMs as safe and efficient synthetic vectors for siRNA delivery. Specifically, a novel polymer (9N) was identified for efficient siRNA delivery to cancer cells and will be further evaluated. PMID:21793212

Cell-micropatterning by micromolding in capillary technique based on UV polymerization

NASA Astrophysics Data System (ADS)

Park, Min J.; Choi, Won M.; Park, O. O.

2006-01-01

Although optical lithography or photolithography is one of the most well-established techniques for micro, nano-fabrication, its usage with proteins and cells is restricted by steps that must be carried out in harsh organic solvents. Here, we present simple methods for cell-micropatterning using poly(dimethylsiloxane) (PDMS) as a mold. Cell non-adhesive surface or nonfouling surface providing a physico-chemical barrier to cell attachment was introduced for biomaterial pattering, where cells fail to interact with the surface over desired periods of time determined by each application. Poly(ethylene glycol) (PEG) was selected as nonfouling material to inhibit protein adsorption from biological media. The fouling resistance of PEG polymer is often explained by a steric repulsion interaction, resulting from the compression of PEG chains as proteins approach the surface. We also chose fibronectin to direct cell attachment because it is an extracellular matrix protein that is involved in the adhesion and spreading of anchorage-dependent cells. In our experiment, we propose two methods by application of micromolding in capillary (MIMIC) method based on UV polymerization to obtain a surface of alternating PEG and fibronectin. First to fabricate PEG microstructure via MIMIC method, a pre-patterned PDMS mold is placed on a desired substrate, and then the relief structure in the mold forms a network of empty channels. A drop of ethylene glycol monomer solution containing initiator for UV polymerization is placed at the open ends of the network of channels, which is then polymerized by exposure to UV light at room temperature. Once PEG microstructure is fabricated, incubation of the patterned surface in a fibronectin-containing solution allows back-filling of only the bare regions with fibronectin via adsorption. In the alternative method, a substrate is first incubated in a fibronectin-containing solution, leading to the adsorption of fibronectin over the entire surface, and the fibronectin-adsorbed substrate is then micropatterned with the PEG by MIMIC based on UV polymerization. Both methods create reproducible alternating PEG and fibronectin patterns applicable to cell-surface interactions on the microscale.

Influence of alkyl chain length compatibility on microemulsion structure and solubilization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bansal, V.K.; O'Connell, J.P.; Shah, D.O.

1980-06-01

The water solubilization capacity of water/oil microemulsions is studied as a function of alkyl chain length of oil (C/sub 8/ to C/sub 16/), surfactant (C/sub 14/ and C/sub 18/ fatty acid soaps), and alcohol (C/sub 4/ to C/sub 7/). Sodium stearate and sodium myristate were used as surfactants. For n-butanol microemulsions the maximum amount of water solubilized in the microemulsion decreased continuously with increasing oil chain length; for n-heptanol it increased continuously. For n-pentanol and n-hexanol systems, water solubilization reached a maximum when the oil chain length plus alcohol chain length was equal to that of the surfactant. The electricmore » resistance and dielectric constant of the microemulsions also are measured as a function of alkyl chain length of the oil. 48 references.« less

Side-Chain Effects on the Thermoelectric Properties of Fluorene-Based Copolymers.

PubMed

Liang, Ansheng; Zhou, Xiaoyan; Zhou, Wenqiao; Wan, Tao; Wang, Luhai; Pan, Chengjun; Wang, Lei

2017-09-01

Three conjugated polymers with alkyl chains of different lengths are designed and synthesized, and their structure-property relationship as organic thermoelectric materials is systematically elucidated. All three polymers show similar photophysical properties, thermal properties, and mechanical properties; however, their thermoelectric performance is influenced by the length of their side chains. The length of the alkyl chain significantly influences the electrical conductivity of the conjugated polymers, and polymers with a short alkyl chain exhibit better conductivity than those with a long alkyl chain. The length of the alkyl chain has little effect on the Seebeck coefficient. Only a slight increase in the Seebeck coefficient is observed with the increasing length of the alkyl chain. The purpose of this study is to provide comprehensive insight into fine-tuning the thermoelectric properties of conjugated polymers as a function of side-chain engineering, thereby providing a novel perspective into the design of high-performance thermoelectric conjugated polymers. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Opening of DNA chain due to force applied on different locations.

PubMed

Singh, Amar; Modi, Tushar; Singh, Navin

2016-09-01

We consider a homogeneous DNA molecule and investigate the effect of random force applied on the unzipping profile of the molecule. How the critical force varies as a function of the chain length or number of base pairs is the objective of this study. In general, the ratio of the critical forces that is applied on the middle of the chain to that which is applied on one of the ends is two. Our study shows that this ratio depends on the length of the chain. This means that the force which is applied to a point can be experienced by a section of the chain. Beyond a length, the base pairs have no information about the applied force. In the case when the chain length is shorter than this length, this ratio may vary. Only in the case when the chain length exceeds a critical length, this ratio is found to be two. Based on the de Gennes formulation, we developed a method to calculate these forces at zero temperature. The exact results at zero temperature match numerical calculations.

Optimization of the elution buffer and concentration method for detecting hepatitis E virus in swine liver using a nested reverse transcription-polymerase chain reaction and real-time reverse transcription-polymerase chain reaction.

PubMed

Son, Na Ry; Seo, Dong Joo; Lee, Min Hwa; Seo, Sheungwoo; Wang, Xiaoyu; Lee, Bog-Hieu; Lee, Jeong-Su; Joo, In-Sun; Hwang, In-Gyun; Choi, Changsun

2014-09-01

The aim of this study was to develop an optimal technique for detecting hepatitis E virus (HEV) in swine livers. Here, three elution buffers and two concentration methods were compared with respect to enhancing recovery of HEV from swine liver samples. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and nested RT-PCR were performed to detect HEV RNA. When phosphate-buffered saline (PBS, pH 7.4) was used to concentrate HEV in swine liver samples using ultrafiltration, real-time RT-PCR detected HEV in 6 of the 26 samples. When threonine buffer was used to concentrate HEV using polyethylene glycol (PEG) precipitation and ultrafiltration, real-time RT-PCR detected HEV in 1 and 3 of the 26 samples, respectively. When glycine buffer was used to concentrate HEV using ultrafiltration and PEG precipitation, real-time RT-PCR detected HEV in 1 and 3 samples of the 26 samples, respectively. When nested RT-PCR was used to detect HEV, all samples tested negative regardless of the type of elution buffer or concentration method used. Therefore, the combination of real-time RT-PCR and ultrafiltration with PBS buffer was the most sensitive and reliable method for detecting HEV in swine livers. Copyright © 2014 Elsevier B.V. All rights reserved.

Constraints on food chain length arising from regional metacommunity dynamics

PubMed Central

Calcagno, Vincent; Massol, François; Mouquet, Nicolas; Jarne, Philippe; David, Patrice

2011-01-01

Classical ecological theory has proposed several determinants of food chain length, but the role of metacommunity dynamics has not yet been fully considered. By modelling patchy predator–prey metacommunities with extinction–colonization dynamics, we identify two distinct constraints on food chain length. First, finite colonization rates limit predator occupancy to a subset of prey-occupied sites. Second, intrinsic extinction rates accumulate along trophic chains. We show how both processes concur to decrease maximal and average food chain length in metacommunities. This decrease is mitigated if predators track their prey during colonization (habitat selection) and can be reinforced by top-down control of prey vital rates (especially extinction). Moreover, top-down control of colonization and habitat selection can interact to produce a counterintuitive positive relationship between perturbation rate and food chain length. Our results show how novel limits to food chain length emerge in spatially structured communities. We discuss the connections between these constraints and the ones commonly discussed, and suggest ways to test for metacommunity effects in food webs. PMID:21367786

Electrostatic contribution to the persistence length of a semiflexible dipolar chain.

PubMed

Podgornik, Rudi

2004-09-01

We investigate the electrostatic contribution to the persistence length of a semiflexible polymer chain whose segments interact via a screened Debye-Hückel dipolar interaction potential. We derive the expressions for the renormalized persistence length on the level of a 1/D-expansion method already successfully used in other contexts of polyelectrolye physics. We investigate different limiting forms of the renormalized persistence length of the dipolar chain and show that, in, general, it depends less strongly on the screening length than in the context of a monopolar chain. We show that for a dipolar chain the electrostatic persistence length in the same regime of the parameter phase space as the original Odijk-Skolnick-Fixman (OSF) form for a monopolar chain depends logarithmically on the screening length rather than quadratically. This can be understood solely on the basis of a swifter decay of the dipolar interactions with separation compared to the monopolar electrostatic interactions. We comment also on the general contribution of higher multipoles to the electrostatic renormalization of the bending rigidity.

Collagenase-labile polyurethane urea synthesis and processing into hollow fiber membranes.

PubMed

Fu, Hui-Li; Hong, Yi; Little, Steven R; Wagner, William R

2014-08-11

As a means to stimulate wound healing, a hollow fiber membrane system might be placed within a wound bed to provide local and externally regulated controlled delivery of regenerative factors. After sufficient healing, it would be desirable to triggerably degrade these fibers as opposed to pulling them out. Accordingly, a series of enzymatically degradable thermoplastic elastomers was developed as potential hollow fiber base material. Polyurethane ureas (PUUs) were synthesized based on 1, 4-diisocyanatobutane, polycaprolactone (PCL) diol and polyethylene glycol (PEG) at different molar fractions as soft segments, and collagenase-sensitive peptide GGGLGPAGGK-NH2 as a chain extender (defined as PUU-CLxEGy-peptide, where x and y are the respective molar percents). In these polymers, PEG in the polymer backbone decreased tensile strengths and initial moduli of solvent-cast films in the wet state, while increasing water absorption. Collagenase degradation was observed at 75% relative PEG content in the soft segment. Control PUUs with putrescine or nonsense peptide chain extenders did not degrade acutely in collagenase. Conduits electrospun from PUU-CL25EG75-peptide and PUU-CL50EG50-peptide exhibited appropriate mechanical strength and sustained release of a model protein from the tube lumen for 7 days. Collapse of PUU-CL25EG75-peptide tubes occurred after collagenase degradation for 3 days. In conclusion, through molecular design, synthesis and characterization, a collagenase-labile PUU-CL25EG75-peptide polymer was identified that exhibited the desired traits of triggerable lability, processability, and the capacity to act as a membrane to facilitate controlled protein release.

Two-step recrystallization of water in concentrated aqueous solution of poly(ethylene glycol).

PubMed

Gemmei-Ide, Makoto; Motonaga, Tetsuya; Kasai, Ryosuke; Kitano, Hiromi

2013-02-21

Crystallization behavior of water in a concentrated aqueous solution of poly(ethylene glycol) (PEG) with a water content of 37.5 wt % was investigated by temperature variable mid-infrared (mid-IR) spectroscopy in a temperature range of 298-170 K. The mid-IR spectrum of water at 298 K showed that a large water cluster was not formed and that most of the water molecules were associated with the PEG chain. Ice formation, however, occurred as found in previous studies by differential scanning calorimetory. Ice formations were grouped into three types: crystallization at 231 K during cooling, that at 198 K during heating, and that at 210 K during heating. The latter two were just recrystallization. These ice formations were the direct transition from hydration species to ice without condensation regardless of crystallization or recrystallization. This means that the recrystallized water in the present system was not generated from low-density amorphous solid water. At a low cooling rate, nearly complete crystallization at 231 K during cooling and no recrystallization were observed. At a high cooling rate, no crystallization and two-step recrystallization at 198 and 210 K were observed. The former and latter recrystallizations were found to be generated from water associated with the PEG chains with ttg (the sequence -O-CH(2)-CH(2)-O- having a trans (t) conformation about the -C-O- bond and a gauche (g) conformation about the -C-C- bond) and random conformations, respectively. These results indicate that recrystallizable water does not have a single specific water structure.

Synthesis and evaluation of sensitizer drug photorelease chemistry: Micro-optic method applied to singlet oxygen generation and drug delivery

NASA Astrophysics Data System (ADS)

Ghosh, Goutam

This thesis summarizes a new micro-optic method for singlet oxygen generation and sensitizer drug delivery, which include i) synthesis and evaluation of a first generation device for drug delivery from native and fluorinated silica probe tips, ii) synthesis of PEG conjugated sensitizers to study phototoxicity in ovarian cancer cells, and iii) synthesis and evaluation of tris-PEGylated chlorin conjugated fluorinated silica for its future integration into the device to use as a 2nd generation device. A first generation micro-optic device was developed that works by sparging O2 gas and light generating cytotoxic singlet oxygen that cleaves the covalently attached drug (sensitizer) from the probe tip at the distal end of the fiber. The aim is to develop a 1st and 2nd generation device for site specific delivery of photosensitizer and singlet oxygen to overcome the challenges involved in systemic administration of the sensitizer. Synthesis and evaluation of drug (pheophorbide-a) delivery applying micro-optic method from native and fluorinated silica probe tip was achieved. The amount of sensitizer photocleavage depends on the loading level of sensitizer onto the probe tips. We also found that photorelease efficiency depends on the nature of the solvents where sensitizer is photocleaved. For example, no photorelease was observed in an aqueous solvent where sensitizer remained adsorbed to the native silica probe-tip. But, 90% photocleavage was obtained in octanol. A significant amount of photosensitizer (formate ester of pyropheophorbide- a) diffused into the liposome when photocleavage study was carried out in liposome. Substantial increase of photorelease was observed in organic solvent when pyropheophorbide-a (PPa) sensitizer was attached to the partially fluorinated porous Vycor glass. We also explored sensitizer photorelease from the fluorinated silica surface at various temperatures and we found that autocatalytic photorelease happened at room temperature and above. No photorelease was observed at low temperature. Chlorin e6 and its one, two and three short chain methoxy triethylene glycol (PEG) conjugated derivatives were synthesized. A comparative study of photocytotoxicity and cellular uptake between each showed that 17 3,152,131- chlorin e6 methoxy triethylene glycol triester has the highest photocytotoxic activity and uptake by ovarian OVCAR-5 cancer cells. Therefore, we decided to load three short chain PEG conjugated chlorin e6 onto the silica surface through spacer alkene for delivery via a fiber-optic probe tip. In order to load chlorin e6-triPEG ester conjugate, in chapter 4, we explored different synthetic strategies. We have been successful in synthesizing spacer alkene succinate linker conjugated chlorin e6 -tri PEG ester, which was attached to the fiber-optic probe tip. Reactions were carried out in mild conditions to avoid detachment of the PEG ester from the carboxylic acid sites of chlorin. Photocleavage of the triPEG modified fluorinated probe tip system was studied in n-butanol.

Injectable hyperbranched poly(β-amino ester) hydrogels with on-demand degradation profiles to match wound healing processes.

PubMed

Xu, Qian; Guo, Linru; A, Sigen; Gao, Yongsheng; Zhou, Dezhong; Greiser, Udo; Creagh-Flynn, Jack; Zhang, Hong; Dong, Yixiao; Cutlar, Lara; Wang, Fagang; Liu, Wenguang; Wang, Wei; Wang, Wenxin

2018-02-28

Adjusting biomaterial degradation profiles to match tissue regeneration is a challenging issue. Herein, biodegradable hyperbranched poly(β-amino ester)s (HP-PBAEs) were designed and synthesized via "A2 + B4" Michael addition polymerization, and displayed fast gelation with thiolated hyaluronic acid (HA-SH) via a "click" thiol-ene reaction. HP-PBAE/HA-SH hydrogels showed tunable degradation profiles both in vitro and in vivo using diamines with different alkyl chain lengths and poly(ethylene glycol) diacrylates with varied PEG spacers. The hydrogels with optimized degradation profiles encapsulating ADSCs were used as injectable hydrogels to treat two different types of humanized excisional wounds - acute wounds with faster healing rates and diabetic wounds with slower healing and neo-tissue formation. The fast-degrading hydrogel showed accelerated wound closure in acute wounds, while the slow-degrading hydrogel showed better wound healing for diabetic wounds. The results demonstrate that the new HP-PBAE-based hydrogel in combination with ADSCs can be used as a well-controlled biodegradable skin substitute, which demonstrates a promising approach in the treatment of various types of skin wounds.

Pharmacokinetics of differently designed immunoliposome formulations in rats with or without hepatic colon cancer metastases.

PubMed

Koning, G A; Morselt, H W; Gorter, A; Allen, T M; Zalipsky, S; Kamps, J A; Scherphof, G L

2001-09-01

Compare pharmacokinetics of tumor-directed immunoliposomes in healthy and tumor-bearing rats (hepatic colon cancer metastases). A tumor cell-specific monoclonal antibody was attached to polyethyleneglycol-stabilized liposomes, either in a random orientation via a lipid anchor (MPB-PEG-liposomes) or uniformly oriented at the distal end of the PEG chains (Hz-PEG-liposomes). Pharmacokinetics and tissue distribution were determined using [3H]cholesteryloleylether or bilayer-anchored 5-fluoro[3H]deoxyuridine-dipalmitate ([3H]FUdR-dP) as a marker. In healthy animals clearance of PEG-(immuno)liposomes was almost log-linear and only slightly affected by antibody attachment; in tumor-bearing animals all liposomes displayed biphasic clearance. In normal and tumor animals blood elimination increased with increasing antibody density; particularly for the Hz-PEG-liposomes, and was accompanied by increased hepatic uptake, probably due to increased numbers of macrophages induced by tumor growth. The presence of antibodies on the liposomes enhanced tumor accumulation: uptake per gram tumor tissue (2-4% of dose) was similar to that of liver. Remarkably, this applied to tumor-specific and irrelevant antibody. Increased immunoliposome uptake by trypsin-treated Kupffer cells implicated involvement of high-affinity Fc-receptors on activated macrophages. Tumor growth and immunoliposome characteristics (antibody density and orientation) determine immunoliposome pharmacokinetics. Although with a long-circulating immunoliposome formulation, efficiently retaining the prodrug FUdR-dP, we achieved enhanced uptake by hepatic metastases, this was probably not mediated by specific interaction with the tumor cells, but rather by tumor-associated macrophages.

Curcumin mediated down-regulation of αV β3 integrin and up-regulation of pyruvate dehydrogenase kinase 4 (PDK4) in Erlotinib resistant SW480 colon cancer cells.

PubMed

Javadi, Samira; Rostamizadeh, Kobra; Hejazi, Jalal; Parsa, Maliheh; Fathi, Mojtaba

2018-02-01

Erlotinib is a potent, selective, and orally active inhibitor of the epidermal growth factor receptor, but the development of erlotinib resistance during chemotherapy can lead to treatment failure. To shed light on the erlotinib-resistant pathway, this study investigated the effect of combination therapy using curcumin- and erlotinib-loaded nanoparticles on the expression of α v β 3 integrin and pyruvate dehydrogenase kinase 4 (PDK4) in an erlotinib-resistant SW480 colon cancer cell line. An erlotinib-resistant SW480 colon cancer cell line was produced by long-term exposure to erlotinib. Curcumin-loaded Methoxy poly ethylene glycol Poly caprolactone (cur/mPEG-PCL) and erlotinib-loaded mPEG-PCL (erl/mPEG-PCL) micelles were provided using a single step nanoprecipitation method and used as combination therapy of resistant SW480 cancer cells. After that, gene expression levels of PDK4, αv, and β3 mRNA were determined by the semiquantitative reverse transcription-polymerase chain reaction. Protein levels of whole α v β 3 integrin were evaluated using the enzyme-linked immunosorbent assay method. In SW480 cell line, the IC50 of nonresistant and resistant cells was 87.6 ± 1.2 nM and 19.1 ± 0.14 μM, for erlotinib and it was about 21.8 and 30 μM for curcumin, respectively. Although PDK4 expression was not significantly different in resistant and nonresistant cells, its expression was up regulated (1.4 fold) in resistant cells by a combination therapy of cur/mPEG-PCL at a dose of 3 μM and erl/mPEG-PCL at a dose of 5 μM. β 3 mRNA and the protein level of whole α v β 3 integrin was significantly higher in resistant SW480 cells as compared with those in nonresistant cells. In terms of treatment, a combination of 6-μM cur/mPEG-PCL and 5-μM erl/mPEG-PCL down regulated β 3 gene expression 6.6-fold in resistant cells as compared with nonresistant cells. At the protein level, a combination of 3-μM-cur/mPEG-PCL and 10-μM erl/mPEG-PCL reduced α v β 3 protein in resistant cells. The results indicated that combination therapy using cur/mPEG-PCL and erl/mPEG-PCL could decrease α v β 3 integrin expression and increase PDK4 gene expression in resistant colon cancer cells, which may have effects on drug resistance signaling pathways. Copyright © 2017 John Wiley & Sons, Ltd.

Strong Stretching of Poly(ethylene glycol) Brushes Mediated by Ionic Liquid Solvation.

PubMed

Han, Mengwei; Espinosa-Marzal, Rosa M

2017-09-07

We have measured forces between mica surfaces coated with a poly(ethylene glycol) (PEG) brush solvated by a vacuum-dry ionic liquid, 1-ethyl-3-methyl imidazolium bis(trifluoromethylsulfonyl)imide, with a surface forces apparatus. At high grafting density, the solvation mediated by the ionic liquid causes the brush to stretch twice as much as in water. Modeling of the steric repulsion indicates that PEG behaves as a polyelectrolyte; the hydrogen bonding between ethylene glycol and the imidazolium cation seems to effectively charge the polymer brush, which justifies the strong stretching. Importantly, under strong polymer compression, solvation layers are squeezed out at a higher rate than for the neat ionic liquid. We propose that the thermal fluctuations of the PEG chains, larger in the brush than in the mushroom configuration, maintain the fluidity of the ionic liquid under strong compression, in contrast to the solid-like squeezing-out behavior of the neat ionic liquid. This is the first experimental study of the behavior of a polymer brush solvated by an ionic liquid under nanoconfinement.

The effect of epsilon-caproyl/D,L-lactyl unit composition on the hydrolytic degradation of poly(D,L-lactide-ran-epsilon-caprolactone)-poly(ethylene glycol)-poly(D,L-lactide-ran-epsilon-caprolactone).

PubMed

Cho, Hanjin; An, Jeongho

2006-02-01

The degradation of P(DLAX-ran-CLY)-b-PEG-b-P(DLAX-ran-CLY)s ( P(DLAX-ran-CLY): Poly(D,L-lactide-ran-epsilon-caprolactone), PEG: Poly(ethylene glycol), X: D,L-lactyl unit fraction, Y: epsilon-caproyl unit fraction) is investigated. The fraction of DLA in the both end blocks is varied while the overall molecular weight and molecular weight of PEG are kept constant. DSC, XRD and GPC are employed to track the degradation process up to 200 days. Also the change in the surface and cross-sectional morphology is provided by SEM micro-photographs. The result of water absorption and weight loss characterization reveals that the incorporation of DLA in the polyester block could be an effective tool to facilitate degradation as well as water absorption. By tracking the change of molecular weight and polydispersity, chain scission and transport or removal of degraded product from the specimen were found to play a complex role in overall degradation.

Multinuclear NMR studies of single lipid bilayers supported in cylindrical aluminum oxide nanopores.

PubMed

Gaede, Holly C; Luckett, Keith M; Polozov, Ivan V; Gawrisch, Klaus

2004-08-31

Lipid bilayers were deposited inside the 0.2 microm pores of anodic aluminum oxide (AAO) filters by extrusion of multilamellar liposomes and their properties studied by 2H, 31P, and 1H solid-state NMR. Only the first bilayer adhered strongly to the inner surface of the pores. Additional layers were washed out easily by a flow of water as demonstrated by 1H magic angle spinning NMR experiments with addition of Pr3+ ions to shift accessible lipid headgroup resonances. A 13 mm diameter Anopore filter of 60 microm thickness oriented approximately 2.5 x 10(-7) mol of lipid as a single bilayer, corresponding to a total membrane area of about 500 cm2. The 2H NMR spectra of chain deuterated POPC are consistent with adsorption of wavy, tubular bilayers to the inner pore surface. By NMR diffusion experiments, we determined the average length of those lipid tubules to be approximately 0.4 microm. There is evidence for a thick water layer between lipid tubules and the pore surface. The ends of tubules are well sealed against the pore such that Pr3+ ions cannot penetrate into the water underneath the bilayers. We successfully trapped poly(ethylene glycol) (PEG) with a molecular weight of 8000 in this water layer. From the quantity of trapped PEG, we calculated an average water layer thickness of 3 nm. Lipid order parameters and motional properties are unperturbed by the solid support, in agreement with existence of a water layer. Such unperturbed, solid supported membranes are ideal for incorporation of membrane-spanning proteins with large intra- and extracellular domains. The experiments suggest the promise of such porous filters as membrane support in biosensors.

Specific targeting and noninvasive magnetic resonance imaging of an asthma biomarker in the lung using polyethylene glycol functionalized magnetic nanocarriers.

PubMed

Al Faraj, Achraf; Shaik, Asma Sultana; Afzal, Sibtain; Al-Muhsen, Saleh; Halwani, Rabih

2016-05-01

Simultaneous inhibition of IL4 and IL13 via the common receptor chain IL4Rα to block adequately their biologic effects presents a promising therapeutic approach to give the additional relief required for asthma patients. In this study, superparamagnetic iron oxide nanoparticles were conjugated with anti-IL4Rα blocking antibodies via polyethylene glycol (PEG) polymers. The delivery of these blocking antibodies to the inflammatory sites in the lung via the developed nanocarriers was assessed using noninvasive free-breathing pulmonary MRI. Biocompatibility assays confirmed the safety of the developed nanocarriers for pre-clinical investigations. For all the investigated formulations, nanocarriers were found to be very stable at neutral pH. However, the stability noticeably decreased with the PEG length in acidic environment and thus the loaded antibodies were preferentially released. Immunofluorescence and fluorimetry assays confirmed the binding of the nanocarriers to the IL4Rα asthma biomarker. Pulmonary MRI performed using an ultra-short echo time sequence allowed simultaneous noninvasive monitoring of inflammatory responses induced by ovalbumin challenge and tracking of the developed nanocarriers, which were found to colocalize with the inflammatory sites in the lung. Targeting of the developed nanocarriers to areas rich in IL4Rα positive inflammatory cells was confirmed using histological and flow cytometry analyses. The anti-IL4Rα-conjugated nanocarriers developed here have been confirmed to be efficient in targeting key inflammatory cells during chronic lung inflammation following intrapulmonary administration. Targeting efficiency was monitored using noninvasive MRI, allowing detection of the nanocarriers' colocalizations with the inflammatory sites in the lung of ovalbumin-challenged asthmatic mice. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

[Impact of priming on seed germination and seedling growth of Oldenlandia diffusa under drought stress].

PubMed

Zhu, Zai-Biao; Lu, Wei-Wei; Guo, Qiao-Sheng; Cao, Ya-Yue; Feng, Shan; Ning, Zi-Jun

2014-04-01

Current study was carried out to optimize the priming condition of Oldenlandia diffusa seeds, and improve germination rate and seed vigor of 0. diffusa seeds under drought conditions. Uniform design was used to optimize the concentration and priming time of three priming materials (PEG, KNO3, GA3). Different concentrations of polyethylene glycol (PEG) was used to simulate drought stress. The seedling was cultured in 1/4 Hoagland medium for 30 d. The results showed that seed priming treatment with 366 mg x kg(-1) GA3 for 1h resulted in significant increase in germination rate, germination index, vigor, root length, plant height and biomass of O. diffusa seeds under drought stress (15% PEG), while seed priming with 3.0% KNO3 for 1 h showed little effect on germination and growth of O. diffusa seeds under drought stress. Seed priming treatment with appropriate GA3 concentration and priming time could enhance seed germination and drought resistance of O. diffusa in seedling stage.

Effect of PEG-PDMAEMA Block Copolymer Architecture on Polyelectrolyte Complex Formation with Heparin.

PubMed

Välimäki, Salla; Khakalo, Alexey; Ora, Ari; Johansson, Leena-Sisko; Rojas, Orlando J; Kostiainen, Mauri A

2016-09-12

Heparin is a naturally occurring polyelectrolyte consisting of a sulfated polysaccharide backbone. It is widely used as an anticoagulant during major surgical operations. However, the associated bleeding risks require rapid neutralization after the operation. The only clinically approved antidote for heparin is protamine sulfate, which is, however, ineffective against low molecular weight heparin and can cause severe adverse reactions in patients. In this study, the facile synthesis of cationic-neutral diblock copolymers and their effective heparin binding is presented. Poly(ethylene glycol)-poly(2-(dimethylamino)ethyl methacrylate) (PEG-PDMAEMA) block copolymers were synthesized in two steps via atom-transfer radical polymerization (ATRP) using PEG as a macroinitiator. Solution state binding between heparin and a range of PEG-PDMAEMA block copolymers and one homopolymer was studied with dynamic light scattering and methylene blue displacement assay. Also in vitro binding in plasma was studied by utilizing a chromogenic heparin anti-Xa assay. Additionally, quartz crystal microbalance and multiparametric surface plasmon resonance were used to study the surface adsorption kinetics of the polymers on a heparin layer. It was shown that the block copolymers and heparin form electrostatically bound complexes with varying colloidal properties, where the block lengths play a key role in controlling the heparin binding affinity, polyelectrolyte complex size and surface charge. With the optimized polymers (PEG114PDMAEMA52 and PEG114PDMAEMA100), heparin could be neutralized in a dose-dependent manner, and bound efficiently into small neutral complexes, with a hydrodynamic radius less than 100 nm. These complexes had only a limited effect on cell viability. Based on these studies, our approach paves the way for the development of new polymeric heparin binding agents.

DNA compaction by poly (amido amine) dendrimers of ammonia cored and ethylene diamine cored

NASA Astrophysics Data System (ADS)

Qamhieh, K.; Al-Shawwa, J.

2017-06-01

The complexes build-up of DNA and soft particles poly amidoamine (PAMAM) dendrimers of ammonia cored of generations (G1-G6) and ethylenediamine cored of generations (G1-G10) have been studied, using a new theoretical model developed by Qamhieh and coworkers. The model describes the interaction between linear polyelectrolyte (LPE) chain and ion-penetrable spheres. Many factors affecting LPE/dendrimer complex have been investigated such as dendrimer generation, the Bjerrum length, salt concentration, and rigidity of the LPE chain represented by the persistence length. It is found that the wrapping chain length around dendrimer increases by increasing dendrimer`s generation, Bjerrum length, and salt concentration, while decreases by increasing the persistence length of the LPE chain. Also we can conclude that the wrapping length of LPE chain around ethylenediamine cored dendrimers is larger than its length around ammonia cored dendrimers.

PEGylated (NH4)xWO3 nanorods as efficient and stable multifunctional nanoagents for simultaneous CT imaging and photothermal therapy of tumor.

PubMed

Macharia, Daniel K; Tian, Qiyun; Chen, Liang; Sun, Yingqi; Yu, Nuo; He, Chuanglong; Wang, Han; Chen, Zhigang

2017-09-01

The simultaneous imaging and photothermal therapy of tumors have attracted much attention, and a prerequisite is to obtain multifunctional nanomaterials. Ideally, one kind of nanoparticles with single component can be used as both imaging agent and photothermal agent. Herein, we have developed the PEGylated (NH 4 ) x WO 3 (denoted as (NH 4 ) x WO 3 -PEG) nanorods as multifunctional nanoparticles with single semiconductor component. (NH 4 ) x WO 3 -PEG nanorods with about 30nm diameter and length of several hundred nanometers have been obtained through a solvothermal synthesis-PEGylation two-step route. Under the irradiation of 980-nm laser with intensity of 0.72Wcm -2 , aqueous dispersion of (NH 4 ) x WO 3 -PEG nanorods (0.67-5.44mmol/L) displays high elevation (17.6-34.5°C) of temperature in 400s, accompanied by an excellent long-term photothermal stability. Furthermore, (NH 4 ) x WO 3 -PEG nanorods exhibit as high as 6 times X-ray attenuation ability compared to that of the clinically used iodine-based X-ray computed tomography (CT) contrast agent (Iopromide). More importantly, after PBS solution of (NH 4 ) x WO 3 -PEG nanorods is injected into the tumor of mice, the tumor can be effectively detected by CT imaging. Moreover, cancer cells in vivo can be further destroyed by the photothermal effects of (NH 4 ) x WO 3 -PEG nanorods, under the irradiation of 980-nm laser with the safe intensity of 0.72Wcm -2 for 10min. Therefore, (NH 4 ) x WO 3 -PEG nanorods can be used as a new kind of stable and efficient multifunctional nanoagent with single component for simultaneous CT imaging and photothermal therapy of tumor. Copyright © 2017. Published by Elsevier B.V.

Tunable evolutions of shock absorption and energy partitioning in magnetic granular chains

NASA Astrophysics Data System (ADS)

Leng, Dingxin; Liu, Guijie; Sun, Lingyu

2018-01-01

In this paper, we investigate the tunable characteristics of shock waves propagating in one-dimensional magnetic granular chains at various chain lengths and magnetic flux densities. According to the Hertz contact theory and Maxwell principle, a discrete element model with coupling elastic and field-induced interaction potentials of adjacent magnetic grains is proposed. We also present hard-sphere approximation analysis to describe the energy partitioning features of magnetic granular chains. The results demonstrate that, for a fixed magnetic field strength, when the chain length is greater than two times of the wave width of the solitary wave, the chain length has little effect on the output energy of the system; for a fixed chain length, the shock absorption and energy partitioning features of magnetic granular chains are remarkably influenced by varying magnetic flux densities. This study implies that the magnetic granular chain is potential to construct adaptive shock absorption components for impulse mitigation.

Lactulose vs polyethylene glycol 3350--electrolyte solution for treatment of overt hepatic encephalopathy: the HELP randomized clinical trial.

PubMed

Rahimi, Robert S; Singal, Amit G; Cuthbert, Jennifer A; Rockey, Don C

2014-11-01

Hepatic encephalopathy (HE) is a common cause of hospitalization in patients with cirrhosis. Pharmacologic treatment for acute (overt) HE has remained the same for decades. To compare polyethylene glycol 3350-electrolyte solution (PEG) and lactulose treatments in patients with cirrhosis admitted to the hospital for HE. We hypothesized that rapid catharsis of the gut using PEG may resolve HE more effectively than lactulose. The HELP (Hepatic Encephalopathy: Lactulose vs Polyethylene Glycol 3350-Electrolyte Solution) study is a randomized clinical trial in an academic tertiary hospital of 50 patients with cirrhosis (of 186 screened) admitted for HE. Participants were block randomized to receive treatment with PEG, 4-L dose (n = 25), or standard-of-care lactulose (n = 25) during hospitalization. The primary end point was an improvement of 1 or more in HE grade at 24 hours, determined using the hepatic encephalopathy scoring algorithm (HESA), ranging from 0 (normal clinical and neuropsychological assessments) to 4 (coma). Secondary outcomes included time to HE resolution and overall length of stay. A total of 25 patients were randomized to each treatment arm. Baseline clinical features at admission were similar in the groups. Thirteen of 25 patients in the standard therapy arm (52%) had an improvement of 1 or more in HESA score, thus meeting the primary outcome measure, compared with 21 of 23 evaluated patients receiving PEG (91%) (P < .01); 1 patient was discharged before final analysis and 1 refused participation. The mean (SD) HESA score at 24 hours for patients receiving standard therapy changed from 2.3 (0.9) to 1.6 (0.9) compared with a change from 2.3 (0.9) to 0.9 (1.0) for the PEG-treated groups (P = .002). The median time for HE resolution was 2 days for standard therapy and 1 day for PEG (P = .01). Adverse events were uncommon, and none was definitely study related. PEG led to more rapid HE resolution than standard therapy, suggesting that PEG may be superior to standard lactulose therapy in patients with cirrhosis hospitalized for acute HE. clinicaltrials.gov Identifier: NCT01283152.

Green tea polyphenol tailors cell adhesivity of RGD displaying surfaces: multicomponent models monitored optically

PubMed Central

Peter, Beatrix; Farkas, Eniko; Forgacs, Eniko; Saftics, Andras; Kovacs, Boglarka; Kurunczi, Sandor; Szekacs, Inna; Csampai, Antal; Bosze, Szilvia; Horvath, Robert

2017-01-01

The interaction of the anti-adhesive coating, poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) and its Arg-Gly-Asp (RGD) functionalized form, PLL-g-PEG-RGD, with the green tea polyphenol, epigallocatechin-gallate (EGCg) was in situ monitored. After, the kinetics of cellular adhesion on the EGCg exposed coatings were recorded in real-time. The employed plate-based waveguide biosensor is applicable to monitor small molecule binding and sensitive to sub-nanometer scale changes in cell membrane position and cell mass distribution; while detecting the signals of thousands of adhering cells. The combination of this remarkable sensitivity and throughput opens up new avenues in testing complicated models of cell-surface interactions. The systematic studies revealed that, despite the reported excellent antifouling properties of the coatings, EGCg strongly interacted with them, and affected their cell adhesivity in a concentration dependent manner. Moreover, the differences between the effects of the fresh and oxidized EGCg solutions were first demonstrated. Using a semiempirical quantumchemical method we showed that EGCg binds to the PEG chains of PLL-g-PEG-RGD and effectively blocks the RGD sites by hydrogen bonds. The calculations supported the experimental finding that the binding is stronger for the oxidative products. Our work lead to a new model of polyphenol action on cell adhesion ligand accessibility and matrix rigidity. PMID:28186133

Bilateral PLA/alginate membranes for the prevention of postsurgical adhesions.

PubMed

Kessler, Martina; Esser, Eva; Groll, Jürgen; Tessmar, Jörg

2016-11-01

A bilateral barrier membrane for the prevention of postsurgical adhesions was developed. Thereby, a smooth PLA side was supposed to keep the affected tissues glidingly separated, while a mucoadhesive side made of alginate was meant to keep the barrier resident on the site of injury so that suturing becomes redundant or at least the membrane stays long enough to facilitate surgical handling. Because hydrophilic alginate and lipophilic PLA films show only low cohesion, solution electrospun meshes of PLA and PLA-PEG-PLA triblock copolymers with varying poly(ethylene glycol) [PEG] content were investigated as cohesion promoter to avoid an easy separation of the functionally different layers. Using direct electrospinning onto the PLA film, a modified contact surface of the mesh was created, which allowed the tested alginate solutions (3%, 5%) to infiltrate to different extents. Thereby, an increasing content of hydrophilic PEG within the mesh copolymer and a lower alginate concentration facilitated the infiltration. As a result, the PLA film with a PLA35k-PEG10k-PLA35k (racemic PLA chains) mesh and an alginate layer cast from a 3% alginate solution appeared to be the most effective combination as examined by means of a t peel test, a mucoadhesion test, a tensile test and optical evaluations. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1563-1570, 2016. © 2015 Wiley Periodicals, Inc.

Green tea polyphenol tailors cell adhesivity of RGD displaying surfaces: multicomponent models monitored optically.

PubMed

Peter, Beatrix; Farkas, Eniko; Forgacs, Eniko; Saftics, Andras; Kovacs, Boglarka; Kurunczi, Sandor; Szekacs, Inna; Csampai, Antal; Bosze, Szilvia; Horvath, Robert

2017-02-10

The interaction of the anti-adhesive coating, poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) and its Arg-Gly-Asp (RGD) functionalized form, PLL-g-PEG-RGD, with the green tea polyphenol, epigallocatechin-gallate (EGCg) was in situ monitored. After, the kinetics of cellular adhesion on the EGCg exposed coatings were recorded in real-time. The employed plate-based waveguide biosensor is applicable to monitor small molecule binding and sensitive to sub-nanometer scale changes in cell membrane position and cell mass distribution; while detecting the signals of thousands of adhering cells. The combination of this remarkable sensitivity and throughput opens up new avenues in testing complicated models of cell-surface interactions. The systematic studies revealed that, despite the reported excellent antifouling properties of the coatings, EGCg strongly interacted with them, and affected their cell adhesivity in a concentration dependent manner. Moreover, the differences between the effects of the fresh and oxidized EGCg solutions were first demonstrated. Using a semiempirical quantumchemical method we showed that EGCg binds to the PEG chains of PLL-g-PEG-RGD and effectively blocks the RGD sites by hydrogen bonds. The calculations supported the experimental finding that the binding is stronger for the oxidative products. Our work lead to a new model of polyphenol action on cell adhesion ligand accessibility and matrix rigidity.

Membranes of Polymers of Intrinsic Microporosity (PIM-1) Modified by Poly(ethylene glycol).

PubMed

Bengtson, Gisela; Neumann, Silvio; Filiz, Volkan

2017-06-05

Until now, the leading polymer of intrinsic microporosity PIM-1 has become quite famous for its high membrane permeability for many gases in gas separation, linked, however, to a rather moderate selectivity. The combination with the hydrophilic and low permeable poly(ethylene glycol) (PEG) and poly(ethylene oxides) (PEO) should on the one hand reduce permeability, while on the other hand enhance selectivity, especially for the polar gas CO₂ by improving the hydrophilicity of the membranes. Four different paths to combine PIM-1 with PEG or poly(ethylene oxide) and poly(propylene oxide) (PPO) were studied: physically blending, quenching of polycondensation, synthesis of multiblock copolymers and synthesis of copolymers with PEO/PPO side chain. Blends and new, chemically linked polymers were successfully formed into free standing dense membranes and measured in single gas permeation of N₂, O₂, CO₂ and CH₄ by time lag method. As expected, permeability was lowered by any substantial addition of PEG/PEO/PPO regardless the manufacturing process and proportionally to the added amount. About 6 to 7 wt % of PEG/PEO/PPO added to PIM-1 halved permeability compared to PIM-1 membrane prepared under similar conditions. Consequently, selectivity from single gas measurements increased up to values of about 30 for CO₂/N₂ gas pair, a maximum of 18 for CO₂/CH₄ and 3.5 for O₂/N₂.

Selective functional activity measurement of a PEGylated protein with a modification-dependent activity assay.

PubMed

Weber, Alfred; Engelmaier, Andrea; Mohr, Gabriele; Haindl, Sonja; Schwarz, Hans Peter; Turecek, Peter L

2017-01-05

BAX 855 (ADYNOVATE) is a PEGylated recombinant factor VIII (rFVIII) that showed prolonged circulatory half-life compared to unmodified rFVIII in hemophilic patients. Here, the development and validation of a novel assay is described that selectively measures the activity of BAX 855 as cofactor for the serine protease factor IX, which actives factor X. This method type, termed modification-dependent activity assay, is based on PEG-specific capture of BAX 855 by an anti-PEG IgG preparation, followed by a chromogenic FVIII activity assay. The assay principle enabled sensitive measurement of the FVIII cofactor activity of BAX 855 down to the pM-range without interference by non-PEGylated FVIII. The selectivity of the capture step, shown by competition studies to primarily target the terminal methoxy group of PEG, also allowed assessment of the intactness of the attached PEG chains. Altogether, the modification-dependent activity not only enriches, but complements the group of methods to selectively, accurately, and precisely measure a PEGylated drug in complex biological matrices. In contrast to all other methods described so far, it allows measurement of the biological activity of the PEGylated protein. Data obtained demonstrate that this new method principle can be extended to protein modifications other than PEGylation and to a variety of functional activity assays. Copyright © 2016 Elsevier B.V. All rights reserved.

Green tea polyphenol tailors cell adhesivity of RGD displaying surfaces: multicomponent models monitored optically

NASA Astrophysics Data System (ADS)

Peter, Beatrix; Farkas, Eniko; Forgacs, Eniko; Saftics, Andras; Kovacs, Boglarka; Kurunczi, Sandor; Szekacs, Inna; Csampai, Antal; Bosze, Szilvia; Horvath, Robert

2017-02-01

The interaction of the anti-adhesive coating, poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) and its Arg-Gly-Asp (RGD) functionalized form, PLL-g-PEG-RGD, with the green tea polyphenol, epigallocatechin-gallate (EGCg) was in situ monitored. After, the kinetics of cellular adhesion on the EGCg exposed coatings were recorded in real-time. The employed plate-based waveguide biosensor is applicable to monitor small molecule binding and sensitive to sub-nanometer scale changes in cell membrane position and cell mass distribution; while detecting the signals of thousands of adhering cells. The combination of this remarkable sensitivity and throughput opens up new avenues in testing complicated models of cell-surface interactions. The systematic studies revealed that, despite the reported excellent antifouling properties of the coatings, EGCg strongly interacted with them, and affected their cell adhesivity in a concentration dependent manner. Moreover, the differences between the effects of the fresh and oxidized EGCg solutions were first demonstrated. Using a semiempirical quantumchemical method we showed that EGCg binds to the PEG chains of PLL-g-PEG-RGD and effectively blocks the RGD sites by hydrogen bonds. The calculations supported the experimental finding that the binding is stronger for the oxidative products. Our work lead to a new model of polyphenol action on cell adhesion ligand accessibility and matrix rigidity.

Effect of Dendritic Polymer Architecture on Biological Behaviors of Self-Assembled Nanocarriers

NASA Astrophysics Data System (ADS)

Hsu, Hao-Jui

Polymeric self-assembled nanocarriers represent one of the most versatile platforms for drug delivery. Through tailoring the physiochemical properties of amphiphilic block copolymers, self-assembled nanocarriers with great thermodynamic stability and desired biological properties could be achieved. The PEGylated dendron-based copolymers (PDCs) are one of the novel amphiphilic copolymers that have attracted a great deal of scientific interest due to their unique dendritic structure and properties. While the dendritic polymer architecture of PDC has been shown to enhance the thermodynamic stability of the self-assembling PDCs, dendron micelles, the effect of this polymer architecture on the biological properties of dendron micelles has not yet been studied. Therefore, this dissertation research is focused on understanding the role of dendritic polymer structure on moderating the biological properties of various self-assembled nanocarriers. To systematically investigate this, three studies have been designed and performed. First, we studied whether the dendritic structure of PDC allows dendron micelles to behave non-specific cellular interactions in a similar way that dendrimers would do. Second, cell-specific interactions of dendron micelles mediated by conjugated ligands were investigated. Third, we investigated the influence of dendritic PEG outer shell on micelle-serum protein interactions and its subsequent implication. Our results revealed that both non-specific and specific cellular interactions of dendron micelles were controllable through modulation of the PEG corona length. While the non-specific charge-dependent cellular interactions of dendron micelles were tunable through controlling the length of PEG corona, the use of long PEG tether was found to enhance the ligand-mediated cellular interactions of dendron micelles. With the ligand tethers, a 27-fold enhancement in ligand-mediated cellular interactions can be achieved, compared to non-targeted dendron micelles. Furthermore, we demonstrate that the dense PEG outer shell introduced by its dendritic structure reduced non-specific micelle-serum protein interactions and suppressed the subsequent micelle disintegration or premature drug release, which was not the case for linear block copolymer (LBC)-based micelles. Molecular dynamic (MD) simulation results also supported that dendron micelles exhibited a weaker interaction with serum albumin compared to LBC-based micelles. In the presence of serum proteins, the half-life of dendron micelles was 2-fold longer than that of LBC-based micelles, which could be attributed to their low serum protein interactions. In conclusion, our results provide fundamental understanding on the role of PEG corona and the effect of polymeric architecture on biological properties of polymer micelles, all indicating that dendron micelles have great potential as a novel drug delivery platform.

Molecular and functional characterization of CaLEA6, the gene for a hydrophobic LEA protein from Capsicum annuum.

PubMed

Kim, Hyung-Sae; Lee, Jee Hyun; Kim, Jae Joon; Kim, Chang-Hoon; Jun, Sung-Soo; Hong, Young-Nam

2005-01-03

We used differential screening to isolate a full-length dehydration-responsive cDNA clone encoding a hydrophobic late embryogenesis abundant (LEA)-like protein from PEG-treated hot pepper leaves. Named CaLEA6 (for Capsicum annuum LEA), this gene belongs to the atypical hydrophobic LEA Group 6. The full-length CaLEA6 is 709 bp long with an open reading frame encoding 164 amino acids. It is predicted to produce a highly hydrophobic, but cytoplasmic, protein. The putative M(r) of CaLEA6 protein is 18 kDa, with a theoretical pI of 4.63. Based on our Southern blot analysis, CaLEA6 appears to exist as a small gene family. CaLEA6 was not expressed prior to any treatment, but its transcript was rapidly and greatly increased following trials with PEG, ABA, and NaCl. Chilling also induced its rapid induction, but to a much lesser extent. Accumulation of CaLEA6 protein occurred soon after NaCl applications, but considerably delayed after treatment with PEG. Tobacco plants that overexpressed CaLEA6 showed enhanced tolerance to dehydration and NaCl but not to chilling, as defined by their leaf fresh weights, Chl contents, and the general health status of the leaves. Therefore, we suggest that CaLEA6 protein plays a potentially protective role when water deficit is induced by dehydration and high salinity, but not low temperature.

Fluorescence Correlation Spectroscopy to Study Diffusion of Polymer Chains within Layered Hydrogen-Bonded Polymer Films

NASA Astrophysics Data System (ADS)

Pristinski, Denis; Kharlampieva, Evguenia; Sukhishvili, Svetlana

2002-03-01

Fluorescence Correlation Spectroscopy (FCS) has been used to probe molecular motions within polymer multilayers formed by hydrogen-bonding sequential self-assembly. Polyethylene glycol (PEG) molecules were end-labeled with the fluorescent tags, and self-assembled with polymethacrylic acid (PMAA) using layer-by-layer deposition. We have found that molecules included in the top adsorbed layer have significant mobility at the millisecond time scale, probably due to translational diffusion. However, their dynamics deviate from classical Brownian motion with a single diffusion time. Possible reasons for the deviation are discussed. We found that motions were significantly slowed with increasing depth within the PEG/PMAA multilayer. This phenomena occured in a narrow pH range around 4.0 in which intermolecular interactions were relatively weak.

Topological analysis of polymeric melts: chain-length effects and fast-converging estimators for entanglement length.

PubMed

Hoy, Robert S; Foteinopoulou, Katerina; Kröger, Martin

2009-09-01

Primitive path analyses of entanglements are performed over a wide range of chain lengths for both bead spring and atomistic polyethylene polymer melts. Estimators for the entanglement length N_{e} which operate on results for a single chain length N are shown to produce systematic O(1/N) errors. The mathematical roots of these errors are identified as (a) treating chain ends as entanglements and (b) neglecting non-Gaussian corrections to chain and primitive path dimensions. The prefactors for the O(1/N) errors may be large; in general their magnitude depends both on the polymer model and the method used to obtain primitive paths. We propose, derive, and test new estimators which eliminate these systematic errors using information obtainable from the variation in entanglement characteristics with chain length. The new estimators produce accurate results for N_{e} from marginally entangled systems. Formulas based on direct enumeration of entanglements appear to converge faster and are simpler to apply.

Glucose-Responsive Trehalose Hydrogel for Insulin Stabilization and Delivery.

PubMed

Lee, Juneyoung; Ko, Jeong Hoon; Mansfield, Kathryn M; Nauka, Peter C; Bat, Erhan; Maynard, Heather D

2018-05-01

Effective delivery of therapeutic proteins is important for many biomedical applications. Yet, the stabilization of proteins during delivery and long-term storage remains a significant challenge. Herein, a trehalose-based hydrogel is reported that stabilizes insulin to elevated temperatures prior to glucose-triggered release. The hydrogel is synthesized using a polymer with trehalose side chains and a phenylboronic acid end-functionalized 8-arm poly(ethylene glycol) (PEG). The hydroxyls of the trehalose side chains form boronate ester linkages with the PEG boronic acid cross-linker to yield hydrogels without any further modification of the original trehalose polymer. Dissolution of the hydrogel is triggered upon addition of glucose as a stronger binder to boronic acid (K b = 2.57 vs 0.48 m -1 for trehalose), allowing the insulin that is entrapped during gelation to be released in a glucose-responsive manner. Moreover, the trehalose hydrogel stabilizes the insulin as determined by immunobinding after heating up to 90 °C. After 30 min heating, 74% of insulin is detected by enzyme-linked immunosorbent assay in the presence of the trehalose hydrogel, whereas only 2% is detected without any additives. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multiscale approach for the construction of equilibrated all-atom models of a poly(ethylene glycol)-based hydrogel

PubMed Central

Li, Xianfeng; Murthy, N. Sanjeeva; Becker, Matthew L.; Latour, Robert A.

2016-01-01

A multiscale modeling approach is presented for the efficient construction of an equilibrated all-atom model of a cross-linked poly(ethylene glycol) (PEG)-based hydrogel using the all-atom polymer consistent force field (PCFF). The final equilibrated all-atom model was built with a systematic simulation toolset consisting of three consecutive parts: (1) building a global cross-linked PEG-chain network at experimentally determined cross-link density using an on-lattice Monte Carlo method based on the bond fluctuation model, (2) recovering the local molecular structure of the network by transitioning from the lattice model to an off-lattice coarse-grained (CG) model parameterized from PCFF, followed by equilibration using high performance molecular dynamics methods, and (3) recovering the atomistic structure of the network by reverse mapping from the equilibrated CG structure, hydrating the structure with explicitly represented water, followed by final equilibration using PCFF parameterization. The developed three-stage modeling approach has application to a wide range of other complex macromolecular hydrogel systems, including the integration of peptide, protein, and/or drug molecules as side-chains within the hydrogel network for the incorporation of bioactivity for tissue engineering, regenerative medicine, and drug delivery applications. PMID:27013229

Fluorescent nanodiamonds embedded in biocompatible translucent shells.

PubMed

Rehor, Ivan; Slegerova, Jitka; Kucka, Jan; Proks, Vladimir; Petrakova, Vladimira; Adam, Marie-Pierre; Treussart, François; Turner, Stuart; Bals, Sara; Sacha, Pavel; Ledvina, Miroslav; Wen, Amy M; Steinmetz, Nicole F; Cigler, Petr

2014-03-26

High pressure high temperature (HPHT) nanodiamonds (NDs) represent extremely promising materials for construction of fluorescent nanoprobes and nanosensors. However, some properties of bare NDs limit their direct use in these applications: they precipitate in biological solutions, only a limited set of bio-orthogonal conjugation techniques is available and the accessible material is greatly polydisperse in shape. In this work, we encapsulate bright 30-nm fluorescent nanodiamonds (FNDs) in 10-20-nm thick translucent (i.e., not altering FND fluorescence) silica shells, yielding monodisperse near-spherical particles of mean diameter 66 nm. High yield modification of the shells with PEG chains stabilizes the particles in ionic solutions, making them applicable in biological environments. We further modify the opposite ends of PEG chains with fluorescent dyes or vectoring peptide using click chemistry. High conversion of this bio-orthogonal coupling yielded circa 2000 dye or peptide molecules on a single FND. We demonstrate the superior properties of these particles by in vitro interaction with human prostate cancer cells: while bare nanodiamonds strongly aggregate in the buffer and adsorb onto the cell membrane, the shell encapsulated NDs do not adsorb nonspecifically and they penetrate inside the cells. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fluorescent Nanodiamonds Embedded in Biocompatible Translucent Shells

PubMed Central

Rehor, Ivan; Slegerova, Jitka; Kucka, Jan; Proks, Vladimir; Petrakova, Vladimira; Adam, Marie-Pierre; Treussart, François; Turner, Stuart; Bals, Sara; Sacha, Pavel; Ledvina, Miroslav; Wen, Amy M.; Steinmetz, Nicole F.; Cigler, Petr

2016-01-01

High pressure high temperature (HPHT) nanodiamonds (NDs) represent extremely promising materials for construction of fluorescent nanoprobes and nanosensors. However, some properties of bare NDs limit their direct use in these applications: they precipitate in biological solutions, only a limited set of bio-orthogonal conjugation techniques is available and the accessible material is greatly polydisperse in shape. In this work, we encapsulate bright 30-nm fluorescent nanodiamonds (FNDs) in 10–20-nm thick translucent (i.e., not altering FND fluorescence) silica shells, yielding monodisperse near-spherical particles of mean diameter 66 nm. High yield modification of the shells with PEG chains stabilizes the particles in ionic solutions, making them applicable in biological environments. We further modify the opposite ends of PEG chains with fluorescent dyes or vectoring peptide using click chemistry. High conversion of this bio-orthogonal coupling yielded circa 2000 dye or peptide molecules on a single FND. We demonstrate the superior properties of these particles by in vitro interaction with human prostate cancer cells: while bare nanodiamonds strongly aggregate in the buffer and adsorb onto the cell membrane, the shell encapsulated NDs do not adsorb nonspecifically and they penetrate inside the cells. PMID:24500945

Surface grafted antibodies: controlled architecture permits enhanced antigen detection.

PubMed

Sebra, Robert P; Masters, Kristyn S; Bowman, Christopher N; Anseth, Kristi S

2005-11-22

The attachment of antibodies to substrate surfaces is useful for achieving specific detection of antigens and toxins associated with clinical and field diagnostics. Here, acrylated whole antibodies were produced through conjugation chemistry, with the goal of covalently photografting these proteins from surfaces in a controlled fashion, to facilitate rapid and sensitive antigenic detection. A living radical photopolymerization chemistry was used to graft the acrylated whole antibodies on polymer surfaces at controlled densities and spatial locations by controlling the exposure time and area, respectively. Copolymer grafts containing these antibodies were synthesized to demonstrate two principles. First, PEG functionalities were introduced to prevent nonspecific protein interactions and improve the reaction kinetics by increasing solvation and mobility of the antibody-containing chains. Both of these properties lead to sensitive (pM) and rapid (<20 min) detection of antigens with this surface modification technique. Second, graft composition was tailored to include multiple antibodies on the same grafted chains, establishing a means for simultaneously detecting multiple antigens on one grafted surface area. Finally, the addition of PEG spacers between the acrylate functionality and the pendant detection antibodies was tuned to enhance the detection of a short-half-life molecule, glucagon, in a complex biological environment, plasma.

Importance of crystallinity of anchoring block of semi-solid amphiphilic triblock copolymers in stabilization of silicone nanoemulsions.

PubMed

Le Kim, Trang Huyen; Jun, Hwiseok; Nam, Yoon Sung

2017-10-01

Polymer emulsifiers solidified at the interface between oil and water can provide exceptional dispersion stability to emulsions due to the formation of unique semi-solid interphase. Our recent works showed that the structural stability of paraffin-in-water emulsions highly depends on the oil wettability of hydrophobic block of methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-b-PCL). Here we investigate the effects of the crystallinity of hydrophobic block of triblock copolymer-based emulsifiers, PCLL-b-PEG-b-PCLL, on the colloidal properties of silicone oil-in-water nanoemulsions. The increased ratio of l-lactide to ε-caprolactone decreases the crystallinity of the hydrophobic block, which in turn reduces the droplet size of silicone oil nanoemulsions due to the increased chain mobility at the interface. All of the prepared nanoemulsions are very stable for a month at 37°C. However, the exposure to repeated freeze-thaw cycles quickly destabilizes the nanoemulsions prepared using the polymer with the reduced crystallinity. This work demonstrates that the anchoring chain crystallization in the semi-solid interphase is critically important for the structural robustness of nanoemulsions under harsh physical stresses. Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical modification of protein A chromatography ligands with polyethylene glycol. I: Effects on IgG adsorption equilibrium, kinetics, and transport.

PubMed

Weinberg, Justin; Zhang, Shaojie; Crews, Gillian; Carta, Giorgio; Przybycien, Todd

2018-04-20

Chemical modification of Protein A (ProA) chromatography ligands with polyethylene glycol (PEGylation) has been proposed as a strategy to increase the process selectivity and resin robustness by providing the ligand with a steric repulsion barrier against non-specific binding. This article comprises a comprehensive study of IgG adsorption and transport in Repligen CaptivA PriMAB resin with PEGylated ProA ligands that are modified using 5.2 and 21.5 kDa PEG chains. We studied the impact of the molecular weight of the PEG as well as the extent of PEGylation for the 5.2 kDa PEG modification. In all cases, PEGylation of ProA ligands decreases the resin average pore size, particle porosity, and static binding capacity for IgG proportional to the volume of conjugated PEG in the resin. Resin batch uptake experiments conducted in bulk via a stirred-tank system and with individual resin particles under confocal laser scanning microscopy suggests that PEGylation introduces heterogeneity into IgG binding kinetics: a fraction of the IgG binding sites are transformed from typical fast association kinetic behavior to slow kinetic behavior. pH gradient elution experiments of an IgG molecule on the modified resins show an increase in IgG elution pH for all modified resins, implying a decrease in IgG-ProA binding affinity on modification. Despite losses in static binding capacity for all resins with PEGylated ligands, the loss of dynamic binding capacity at 10% breakthrough (DBC 10% ) ranged more broadly from almost 0-47% depending on the PEG molecular weight and the extent of PEGylation. Minimal losses in DBC 10% were observed with a low extent of PEGylation with a smaller molecular weight PEG, while higher losses were observed at higher extents of PEGylation and with higher molecular weight PEG due to decreased static binding capacity and increased mass transfer resistance. This work provides insight into the practical implications for resin performance if PEGylation is considered as a strategy for selectivity enhancement in affinity chromatography with macromolecular ligands. Copyright © 2018 Elsevier B.V. All rights reserved.

An equal force theory for network models of soft materials with arbitrary molecular weight distribution

NASA Astrophysics Data System (ADS)

Verron, E.; Gros, A.

2017-09-01

Most network models for soft materials, e.g. elastomers and gels, are dedicated to idealized materials: all chains admit the same number of Kuhn segments. Nevertheless, such standard models are not appropriate for materials involving multiple networks, and some specific constitutive equations devoted to these materials have been derived in the last few years. In nearly all cases, idealized networks of different chain lengths are assembled following an equal strain assumption; only few papers adopt an equal stress assumption, although some authors argue that such hypothesis would reflect the equilibrium of the different networks in contact. In this work, a full-network model with an arbitrary chain length distribution is derived by considering that chains of different lengths satisfy the equal force assumption in each direction of the unit sphere. The derivation is restricted to non-Gaussian freely jointed chains and to affine deformation of the sphere. Firstly, after a proper definition of the undeformed configuration of the network, we demonstrate that the equal force assumption leads to the equality of a normalized stretch in chains of different lengths. Secondly, we establish that the network with chain length distribution behaves as an idealized full-network of which both chain length and density of are provided by the chain length distribution. This approach is finally illustrated with two examples: the derivation of a new expression for the Young modulus of bimodal interpenetrated polymer networks, and the prediction of the change in fluorescence during deformation of mechanochemically responsive elastomers.

Thrombopoietin: biology and clinical potentials.

PubMed

Miyazaki, H; Kato, T

1999-12-01

Thrombopoietin (TPO) is the principal physiologic regulator of platelet production. In vitro, TPO induces the growth of colony-forming units-megakaryocyte (CFU-MK) and the generation of mature polyploid megakaryocytes, which subsequently form extended cytoplasmic processes, termed proplatelets. On more differentiated CFU-MK, but not on megakaryocytes, TPO is critical for enhancing proplatelet formation. TPO has multilineage effects in hematopoiesis, not only stimulating megakaryocytopoiesis but also acting in synergy with other cytokines to enhance proliferation and survival of committed erythroid progenitors and primitive hematopoietic stem cells. Surface c-MPL, the receptor for TPO, defines a phenotype of hematopoietic stem cells with long-term repopulating ability. Treatment with various cytokine combinations, including TPO, results in an extensive ex vivo expansion of hematopoietic stem cells and blood cell precursors. In normal animals, pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) or glycosylated TPO increases the number of bone marrow megakaryocytes and their progenitors and greatly enhance the production of morphologically and functionally normal platelets. In contrast, they have only minimal effects on peripheral white blood cell and red blood cell counts. PEG-rHuMGDF used alone markedly expands circulating levels of multiple types of hematopoietic progenitors, and its effect is enhanced in combination with granulocyte colony-stimulating factor (G-CSF). Although PEG-rHuMGDF augments platelet aggregation induced by agonists in vitro, it has no influence in an animal model of thrombus formation. PEG-rHuMGDF or glycosylated TPO has a profound effect in a variety of animal models of thrombocytopenia, including myelosuppressive therapy. PEG-rHuMGDF treatment accelerates multilineage hematopoietic recovery, effectively improving thrombocytopenia, and, in most models, neutropenia and anemia. The concurrent administration of PEG-rHuMGDF and G-CSF does not interfere with the in vivo activity of cytokines but rather has synergistic effects. To further accelerate hematopoietic recovery, PEG-rHuMGDF administration should start at the earliest time following myelosuppressive treatment; this time sensitivity may result from the presence of a greater number of residual hematopoietic progenitors in the bone marrow soon after treatment. Moreover, if a relatively large dose of PEG-rHuMGDF is administered, a single intravenous injection is fully effective in improving impaired hematopoiesis. This effectiveness appears to be related to the persistence of PEG-rHuMGDF in the circulation. The safety and efficacy of two forms of the recombinant hormone, PEG-rHuMDGF and glycosylated human full-length TPO produced in mammalian cells, are currently under clinical investigation.

Knotting probability of a shaken ball-chain.

PubMed

Hickford, J; Jones, R; du Pont, S Courrech; Eggers, J

2006-11-01

We study the formation of knots on a macroscopic ball chain, which is shaken on a horizontal plate at 12 times the acceleration of gravity. We find that above a certain critical length, the knotting probability is independent of chain length, while the time to shake out a knot increases rapidly with chain length. The probability of finding a knot after a certain time is the result of the balance of these two processes. In particular, the knotting probability tends to a constant for long chains.

Certain Chemical Substances Containing Varying Carbon Chain Lengths (Alkyl Ranges Using the Cx-y Notation) on the TSCA Inventory

EPA Pesticide Factsheets

This paper explains the conventions that are applied to certain listings of chemical substances containing ranges of alkyl chain lengths (i.e., carbon chains of varying lengths) for chemical substances on the Toxic Substances Control Act (TSCA)

A novel dendritic nanocarrier of polyamidoamine-polyethylene glycol-cyclic RGD for “smart” small interfering RNA delivery and in vitro antitumor effects by human ether-à-go-go-related gene silencing in anaplastic thyroid carcinoma cells

PubMed Central

Li, Guanhua; Hu, Zuojun; Yin, Henghui; Zhang, Yunjian; Huang, Xueling; Wang, Shenming; Li, Wen

2013-01-01

The application of RNA interference techniques is promising in gene therapeutic approaches, especially for cancers. To improve safety and efficiency of small interfering RNA (siRNA) delivery, a triblock dendritic nanocarrier, polyamidoamine-polyethylene glycol-cyclic RGD (PAMAM-PEG-cRGD), was developed and studied as an siRNA vector targeting the human ether-à-go-go-related gene (hERG) in human anaplastic thyroid carcinoma cells. Structure characterization, particle size, zeta potential, and gel retardation assay confirmed that complete triblock components were successfully synthesized with effective binding capacity of siRNA in this triblock nanocarrier. Cytotoxicity data indicated that conjugation of PEG significantly alleviated cytotoxicity when compared with unmodified PAMAM. PAMAM-PEG-cRGD exerted potent siRNA cellular internalization in which transfection efficiency measured by flow cytometry was up to 68% when the charge ratio (N/P ratio) was 3.5. Ligand-receptor affinity together with electrostatic interaction should be involved in the nano-siRNA endocytosis mechanism and we then proved that attachment of cRGD enhanced cellular uptake via RGD-integrin recognition. Gene silencing was evaluated by reverse transcription polymerase chain reaction and PAMAM-PEG-cRGD-siRNA complex downregulated the expression of hERG to 26.3% of the control value. Furthermore, gene knockdown of hERG elicited growth suppression as well as activated apoptosis by means of abolishing vascular endothelial growth factor secretion and triggering caspase-3 cascade in anaplastic thyroid carcinoma cells. Our study demonstrates that this novel triblock polymer, PAMAM-PEG-cRGD, exhibits negligible cytotoxicity, effective transfection, “smart” cancer targeting, and therefore is a promising siRNA nanocarrier. PMID:23569377

Poly(ethylene glycol) analogs grafted with low molecular weight poly(ethylene imine) as non-viral gene vectors.

PubMed

Zhang, Zhenfang; Yang, Cuihong; Duan, Yajun; Wang, Yanming; Liu, Jianfeng; Wang, Lianyong; Kong, Deling

2010-07-01

A novel class of non-viral gene vectors consisting of low molecular weight poly(ethylene imine) (PEI) (molecular weight 800 Da) grafted onto degradable linear poly(ethylene glycol) (PEG) analogs was synthesized. First, a Michael addition reaction between poly(ethylene glycol) diacrylates (PEGDA) (molecular weight 258 Da) and d,l-dithiothreitol (DTT) was carried out to generate a linear polymer (PEG-DTT) having a terminal thiol, methacrylate and pendant hydroxyl functional groups. Five PEG-DTT analogs were synthesized by varying the molar ratio of diacrylates to thiols from 1.2:1 to 1:1.2. Then PEI (800 Da) was grafted onto the main chain of the PEG-DTTs using 1,1'-carbonyldiimidazole as the linker. The above reaction gave rise to a new class of non-viral gene vectors, (PEG-DTT)-g-PEI copolymers, which can effectively complex DNA to form nanoparticles. The molecular weights and structures of the copolymers were characterized by gel permeation chromatography, (1)H nuclear magnetic resonance and Fourier transform infrared spectroscopy. The size of the nanoparticles was<200 nm and the surface charge of the nanoparticles, expressed as the zeta potential, was between+20 and+40 mV. Cytotoxicity assays showed that the copolymers exhibited much lower cytotoxicities than high molecular weight PEI (25 kDa). Transfection was performed in cultured HeLa, HepG2, MCF-7 and COS-7 cells. The copolymers showed higher transfection efficiencies than PEI (25 kDa) tested in four cell lines. The presence of serum (up to 30%) had no inhibitory effect on the transfection efficiency. These results indicate that this new class of non-viral gene vectors may be a promising gene carrier that is worth further investigation. Copyright 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Carbonyl Compounds Produced by Vaporizing Cannabis Oil Thinning Agents.

PubMed

Troutt, William D; DiDonato, Matthew D

2017-11-01

Cannabis use has increased in the United States, particularly the use of vaporized cannabis oil, which is often mixed with thinning agents for use in vaporizing devices. E-cigarette research shows that heated thinning agents produce potentially harmful carbonyls; however, similar studies have not been conducted (1) with agents that are commonly used in the cannabis industry and (2) at temperatures that are appropriate for cannabis oil vaporization. The goal of this study was to determine whether thinning agents used in the cannabis industry produce potentially harmful carbonyls when heated to a temperature that is appropriate for cannabis oil vaporization. Four thinning agents (propylene glycol [PG], vegetable glycerin [VG], polyethylene glycol 400 [PEG 400], and medium chain triglycerides [MCT]) were heated to 230°C and the resulting vapors were tested for acetaldehyde, acrolein, and formaldehyde. Each agent was tested three times. Testing was conducted in a smoking laboratory. Carbonyl levels were measured in micrograms per puff block. Analyses showed that PEG 400 produced significantly higher levels of acetaldehyde and formaldehyde than PG, MCT, and VG. Formaldehyde production was also significantly greater in PG compared with MCT and VG. Acrolein production did not differ significantly across the agents. PG and PEG 400 produced high levels of acetaldehyde and formaldehyde when heated to 230°C. Formaldehyde production from PEG 400 isolate was particularly high, with one inhalation accounting for 1.12% of the daily exposure limit, nearly the same exposure as smoking one cigarette. Because PG and PEG 400 are often mixed with cannabis oil, individuals who vaporize cannabis oil products may risk exposure to harmful formaldehyde levels. Although more research is needed, consumers and policy makers should consider these potential health effects before use and when drafting cannabis-related legislation.

Functional PEG–PAMAM-Tetraphosphonate Capped NaLnF4 Nanoparticles and their Colloidal Stability in Phosphate Buffer

PubMed Central

2015-01-01

Developing surface coatings for NaLnF4 nanoparticles (NPs) that provide long-term stability in solutions containing competitive ions such as phosphate remains challenging. An amine-functional polyamidoamine tetraphosphonate (NH2-PAMAM-4P) as a multidentate ligand for these NPs has been synthesized and characterized as a ligand for the surface of NaGdF4 and NaTbF4 nanoparticles. A two-step ligand exchange protocol was developed for introduction of the NH2-PAMAM-4P ligand on oleate-capped NaLnF4 NPs. The NPs were first treated with methoxy-poly(ethylene glycol)-monophosphoric acid (Mn = 750) in tetrahydrofuran. The mPEG750-OPO3-capped NPs were stable colloidal solutions in water, where they could be ligand-exchanged with NH2-PAMAM-4P. The surface amine groups on the NPs were available for derivatization to attach methoxy-PEG (Mn = 2000) and biotin-terminated PEG (Mn = 2000) chains. The surface coverage of ligands on the NPs was examined by thermal gravimetric analysis, and by a HABA analysis for biotin-containing NPs. Colloidal stability of the NPs was examined by dynamic light scattering. NaGdF4 and NaTbF4 NPs capped with mPEG2000–PAMAM-4P showed colloidal stability in DI water and in phosphate buffer (10 mM, pH 7.4). A direct comparison with NaTbF4 NPs capped with a mPEG2000-lysine-based tetradentate ligand that we reported previously (Langmuir2012, 28, 12861−1287022906305) showed that both ligands provided long-term stability in phosphate buffer, but that the lysine-based ligand provided better stability in phosphate-buffered saline. PMID:24898128

Identification of ginsenoside markers from dry purified extract of Panax ginseng by a dereplication approach and UPLC-QTOF/MS analysis.

PubMed

Yang, Heejung; Lee, Dong Young; Kang, Kyo Bin; Kim, Jeom Yong; Kim, Sun Ok; Yoo, Young Hyo; Sung, Sang Hyun

2015-05-10

A dry purified extract of Panax ginseng (PEG) was prepared using a manufacturing process that includes column chromatography, acid hydrolysis, and an enzyme reaction. During the manufacturing process, the more polar ginsenosides were altered into less polar forms via cleavage of their sugar chains and structural modifications of the aglycones, such as hydroxylation and dehydroxylation. The structural changes of ginsenosides during the intermediate steps from dried ginseng extract (DGE) to PEG were monitored by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectroscopy (UPLC-QTOF/MS). 22 ginsenosides isolated from PEG were used as the reference standards for determining of unknown ginsenosides and further suggesting of the metabolic markers. The elution order of 22 ginsenosides based on the type of aglycones, and the location and number of sugar chains can be used for the structural elucidation of unknown ginsenosides. This information could be used in a dereplication process for quick and efficient identification of ginsenoside derivatives in ginseng preparations. A dereplication approach helped the identification of the metabolic markers in the UPLC-QTOF/MS chromatograms during the conversion process with multivariate analyses, including principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) plots. These metabolic markers were identified by comparing with the dereplication information of the reference standards of 22 ginsenosides, or they were assigned using the pattern of the MS/MS fragmented ions. Consequently, the developed metabolic profiling approach using UPLC-QTOF/MS and multivariate analysis represents a new method for providing quality control as well as useful criteria for a similarity evaluation of the manufacturing process of ginseng preparations. Copyright © 2015 Elsevier B.V. All rights reserved.

Concentration dependence of lipopolymer self-diffusion in supported bilayer membranes

PubMed Central

Zhang, Huai-Ying; Hill, Reghan J.

2011-01-01

Self-diffusion coefficients of poly(ethylene glycol)2k-derivatized lipids (DSPE-PEG2k-CF) in glass-supported DOPC phospholipid bilayers are ascertained from quantitative fluorescence recovery after photobleaching (FRAP). We developed a first-order reaction–diffusion model to ascertain the bleaching constant, mobile fraction and lipopolymer self-diffusion coefficient Ds at concentrations in the range c ≈ 0.5–5 mol%. In contrast to control experiments with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(7-nitro-2-1,3-benzoxadiazol-4-yl) (ammonium salt) (DOPE-NBD) in 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), the lipopolymer self-diffusion coefficient decreases monotonically with increasing concentration, without a distinguishing mushroom-to-brush transition. Our data yield a correlation Ds = D0/(1 + αc), where D0 ≈ 3.36 µm2 s−1 and α ≈ 0.56 (with c expressed as a mole percent). Interpreting the dilute limit with the Scalettar–Abney–Owicki statistical mechanical theory for transmembrane proteins yields an effective disc radius ae ≈ 2.41 nm. On the other hand, the Bussell–Koch–Hammer theory, which includes hydrodynamic interactions, yields ae ≈ 2.92 nm. As expected, both measures are smaller than the Flory radius of the 2 kDa poly(ethylene glycol) (PEG) chains, RF ≈ 3.83 nm, and significantly larger than the nominal radius of the phospholipid heads, al ≈ 0.46 nm. The diffusion coefficient at infinite dilution D0 was interpreted using the Evans–Sackmann theory, furnishing an inter-leaflet frictional drag coefficient bs ≈ 1.33 × 108 N s m−3. Our results suggest that lipopolymer interactions are dominated by the excluded volume of the PEG-chain segments, with frictional drag dominated by the two-dimensional bilayer hydrodynamics. PMID:20504804

Rouse mode analysis of chain relaxation in homopolymer melts

DOE PAGES

Kalathi, Jagannathan T.; Kumar, Sanat K.; Rubinstein, Michael; ...

2014-09-15

We use molecular dynamics simulations of the Kremer–Grest (KG) bead–spring model of polymer chains of length between 10 and 500, and a closely related analogue that allows for chain crossing, to clearly delineate the effects of entanglements on the length-scale-dependent chain relaxation in polymer melts. We analyze the resulting trajectories using the Rouse modes of the chains and find that entanglements strongly affect these modes. The relaxation rates of the chains show two limiting effective monomeric frictions, with the local modes experiencing much lower effective friction than the longer modes. The monomeric relaxation rates of longer modes vary approximately inverselymore » with chain length due to kinetic confinement effects. The time-dependent relaxation of Rouse modes has a stretched exponential character with a minimum of stretching exponent in the vicinity of the entanglement chain length. None of these trends are found in models that allow for chain crossing. As a result, these facts, in combination, argue for the confined motion of chains for time scales between the entanglement time and their ultimate free diffusion.« less

Toxicity of single-wall carbon nanotubes functionalized with polyethylene glycol in zebrafish (Danio rerio) embryos.

PubMed

Girardi, Felipe A; Bruch, Gisele E; Peixoto, Carolina S; Dal Bosco, Lidiane; Sahoo, Sangram K; Gonçalves, Carla O F; Santos, Adelina P; Furtado, Clascídia A; Fantini, Cristiano; Barros, Daniela M

2017-02-01

Single-wall carbon nanotubes functionalized with polyethylene glycol (SWCNT-PEG) are promising materials for biomedical applications such as diagnostic devices and controlled drug-release systems. However, several questions about their toxicological profile remain unanswered. Thus, the aim of this study was to investigate the action of SWCNT-PEG in Danio rerio zebrafish embryos at the molecular, physiological and morphological levels. The SWCNT used in this study were synthesized by the high-pressure carbon monoxide process, purified and then functionalized with distearoyl phosphatidylethanolamine block copolymer-PEG (molecular weight 2 kDa). The characterization process was carried out with low-resolution transmission electron microscopy, thermogravimetric analysis and Raman spectroscopy. Individual zebrafish embryos were exposed to the SWCNT-PEG. Toxic effects occurred only at the highest concentration tested (1 ppm) and included high mortality rates, delayed hatching and decreased total larval length. For all the concentrations tested, the alkaline comet assay revealed no genotoxicity, and Raman spectroscopy measurements on the histological slices revealed no intracellular nanotubes. The results shown here demonstrate that SWCNT-PEG has low toxicity in zebrafish embryos, but more studies are needed to understand what mechanisms are involved. However, the presence of residual metals is possibly among the primary mechanisms responsible for the toxic effects observed, because the purification process was not able to remove all metal contamination, as demonstrated by the thermogravimetric analysis. More attention must be given to the toxicity of these nanomaterials before they are used in biomedical applications. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Halopriming of seeds imparts tolerance to NaCl and PEG induced stress in Vigna radiata (L.) Wilczek varieties.

PubMed

Jisha, K C; Puthur, Jos T

2014-07-01

The investigation was carried out to study the effect of halopriming on NaCl and polyethylene glycol-6000 (PEG-6000) induced stress tolerance potential of three Vigna radiata (L.) Wilczek varieties, with varied abiotic stress tolerance potential. Halopriming is a seed priming technique in which the seeds were soaked in various salt solutions (in this study NaCl was used). The results of the study indicated that the application of stresses (both NaCl and PEG) induced retardation of growth attributes (measured in terms of shoot length, fresh weight, dry weight) and decrease in physiological attributes like total chlorophyll content, metabolites, photosynthetic and mitochondrial activity of the seedlings in all three V. radiata (L.) varieties. However, halopriming of the seeds could reduce the extent of decrease in these biological attributes. NaCl and PEG stress also caused increase in MDA content (a product of membrane lipid peroxidation) in all the varieties studied and this increase was significantly minimized under halopriming. From the present investigation it was evident that among the green gram varieties studied, Pusa Vishal, a NaCl tolerant variety showed enhanced tolerance to NaCl and PEG induced stress, when the seeds were subjected to halopriming followed by Pusa Ratna (stress sensitive variety). Pusa 9531 (drought tolerant variety) also showed positive halopriming effects but it was less significant when compared to other two varieties. It could be concluded that halopriming improved the drought and salinity stress tolerance potential of all varieties and it was significantly higher in the Pusa Vishal as compared to Pusa 9531 and Pusa Ratna.

Effects of PEG-induced osmotic stress on growth and dhurrin levels of forage sorghum.

PubMed

O'Donnell, Natalie H; Møller, Birger Lindberg; Neale, Alan D; Hamill, John D; Blomstedt, Cecilia K; Gleadow, Roslyn M

2013-12-01

Sorghum (Sorghum bicolor L. Moench) is a valuable forage crop in regions with low soil moisture. Sorghum may accumulate high concentrations of the cyanogenic glucoside dhurrin when drought stressed resulting in possible cyanide (HCN) intoxication of grazing animals. In addition, high concentrations of nitrate, also potentially toxic to ruminants, may accumulate during or shortly after periods of drought. Little is known about the degree and duration of drought-stress required to induce dhurrin accumulation, or how changes in dhurrin concentration are influenced by plant size or nitrate metabolism. Given that finely regulating soil moisture under controlled conditions is notoriously difficult, we exposed sorghum plants to varying degrees of osmotic stress by growing them for different lengths of time in hydroponic solutions containing polyethylene glycol (PEG). Plants grown in medium containing 20% PEG (-0.5 MPa) for an extended period had significantly higher concentrations of dhurrin in their shoots but lower dhurrin concentrations in their roots. The total amount of dhurrin in the shoots of plants from the various treatments was not significantly different on a per mass basis, although a greater proportion of shoot N was allocated to dhurrin. Following transfer from medium containing 20% PEG to medium lacking PEG, shoot dhurrin concentrations decreased but nitrate concentrations increased to levels potentially toxic to grazing ruminants. This response is likely due to the resumption of plant growth and root activity, increasing the rate of nitrate uptake. Data presented in this article support a role for cyanogenic glucosides in mitigating oxidative stress. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Embryonic catalase protects against ethanol embryopathies in acatalasemic mice and transgenic human catalase-expressing mice in embryo culture.

PubMed

Miller-Pinsler, Lutfiya; Wells, Peter G

2015-09-15

Reactive oxygen species (ROS) have been implicated in the mechanism of ethanol (EtOH) teratogenicity, but the protective role of the embryonic antioxidative enzyme catalase is unclear, as embryonic activity is only about 5% of maternal levels. We addressed this question in a whole embryo culture model. C57BL/6 mouse embryos expressing human catalase (hCat) or their wild-type (C57BL/6 WT) controls, and C3Ga.Cg-Cat(b)/J catalase-deficient, acatalasemic (aCat) mouse embryos or their wild-type C3HeB/FeJ (C3H WT) controls, were explanted on gestational day (GD) 9 (plug=GD 1), exposed for 24h to 2 or 4mg/mL EtOH or vehicle, and evaluated for functional and morphological changes. hCat and C57BL/6 WT vehicle-exposed embryos developed normally, while EtOH was embryopathic in C57BL/6 WT embryos, evidenced by decreases in anterior neuropore closure, somites developed, turning and head length, whereas hCat embryos were protected (p<0.001). Maternal pretreatment of C57BL/6 WT dams with 50kU/kg PEG-catalase (PEG-cat) 8h prior to embryo culture, which increases embryonic catalase activity, blocked all EtOH embryopathies (p<0.001). Vehicle-exposed aCat mouse embryos had lower yolk sac diameters compared to WT controls, suggesting that endogenous ROS are embryopathic. EtOH was more embryopathic in aCat embryos than WT controls, evidenced by reduced head length and somite development (p<0.01), and trends for reduced anterior neuropore closure, turning and crown-rump length. Maternal pretreatment of aCat dams with PEG-Cat blocked all EtOH embryopathies (p<0.05). These data suggest that embryonic catalase is a determinant of risk for EtOH embryopathies. Copyright © 2015 Elsevier Inc. All rights reserved.

PEGylation and Dimerization of Expressed Proteins under Near Equimolar Conditions with Potassium 2-Pyridyl Acyltrifluoroborates

PubMed Central

2018-01-01

The covalent conjugation of large, functionalized molecules remains a frontier in synthetic chemistry, as it requires rapid, chemoselective reactions. The potassium acyltrifluoroborate (KAT)–hydroxylamine amide-forming ligation shows promise for conjugations of biomolecules under aqueous, acidic conditions, but the variants reported to date are not suited to ligations at micromolar concentrations. We now report that 2-pyridyl KATs display significantly enhanced ligation kinetics over their aryl counterparts. Following their facile, one-step incorporation onto the termini of polyethylene glycol (PEG) chains, we show that 2-pyridyl KATs can be applied to the construction of protein–polymer conjugates in excellent (>95%) yield. Four distinct expressed, folded proteins equipped with a hydroxylamine could be PEGylated with 2–20 kDa 2-pyridyl mPEG KATs in high yield and with near-equimolar amounts of coupling partners. Furthermore, the use of a bis 2-pyridyl PEG KAT enables the covalent homodimerization of proteins with good conversion. The 2-pyridyl KAT ligation offers an effective alternative to conventional protein–polymer conjugation by operating under aqueous acidic conditions well suited for the handling of folded proteins. PMID:29532019

Fabrication and biological imaging of polyhedral oligomeric silsesquioxane cross-linked fluorescent polymeric nanoparticles with aggregation-induced emission feature

NASA Astrophysics Data System (ADS)

Mao, Liucheng; Liu, Meiying; Xu, Dazhuang; Wan, Qing; Huang, Qiang; Jiang, Ruming; Shi, Yingge; Deng, Fengjie; Zhang, Xiaoyong; Wei, Yen

2017-11-01

Aggregation-induced emission (AIE) dyes based fluorescent polymeric nanoparticles (FNPs) have been intensively explored for biomedical applications. However, many of these AIE-active FNPs are relied on the self-assembly of amphiphilic copolymers, which are not stable in diluted solution. Therefore, the introduction of cross-linkages into these micelles has demonstrated to be an efficient route to overcome this stability problem and endow ultra-low critical micelle concentrations (CMC) of these AIE-active FNPs. In this work, we reported the fabrication of cross-linked AIE-active FNPs through controllable reversible addition fragmentation chain transfer polymerization by using commercially available octavinyl-T8-silsesquioxane (8-vinyl POSS) as the cross-linkage for the first time. The resultant cross-linked amphiphilic copolymers (named as PEG-POSS-PhE) are prone to self-assemble into stable core-shell nanoparticles with well water dispersity, strong red fluorescence and low CMC (0.0069 mg mL-1) in aqueous solution. More importantly, PEG-POSS-PhE FNPs possess some other properties such as high water dispersity, uniform morphology and small size, excellent biocompatibility and cellular internalization, providing great potential of PEG-POSS-PhE FNPs for biological imaging application.

Supramolecular PEGylation of biopharmaceuticals

PubMed Central

Webber, Matthew J.; Vinciguerra, Brittany; Cortinas, Abel B.; Thapa, Lavanya S.; Jhunjhunwala, Siddharth; Isaacs, Lyle; Langer, Robert; Anderson, Daniel G.

2016-01-01

The covalent modification of therapeutic biomolecules has been broadly explored, leading to a number of clinically approved modified protein drugs. These modifications are typically intended to address challenges arising in biopharmaceutical practice by promoting improved stability and shelf life of therapeutic proteins in formulation, or modifying pharmacokinetics in the body. Toward these objectives, covalent modification with poly(ethylene glycol) (PEG) has been a common direction. Here, a platform approach to biopharmaceutical modification is described that relies on noncovalent, supramolecular host–guest interactions to endow proteins with prosthetic functionality. Specifically, a series of cucurbit[7]uril (CB[7])–PEG conjugates are shown to substantially increase the stability of three distinct protein drugs in formulation. Leveraging the known and high-affinity interaction between CB[7] and an N-terminal aromatic residue on one specific protein drug, insulin, further results in altering of its pharmacological properties in vivo by extending activity in a manner dependent on molecular weight of the attached PEG chain. Supramolecular modification of therapeutic proteins affords a noncovalent route to modify its properties, improving protein stability and activity as a formulation excipient. Furthermore, this offers a modular approach to append functionality to biopharmaceuticals by noncovalent modification with other molecules or polymers, for applications in formulation or therapy. PMID:27911829

Assessment of the structure of pegylated-recombinant protein therapeutics by the NMR fingerprint assay.

PubMed

Hodgson, Derek J; Aubin, Yves

2017-05-10

A number of recombinant protein therapeutic products, such as filgrastim (methionyl granulocyte colony stimulating factor [Met-GCSF] used to boost the immune system in chemotherapy treated cancer patients), and interferon alpha-2 (used for the treatment of various viral infections), have been chemically modified with the addition of a polyethylene glycol (PEG) chain. This modification prolongs residency of the drug in the body and reduces metabolic degradation, which allows less frequent administration of the products. Here we show how NMR spectroscopy methods can assess the higher order structure (HOS) of pegylated-filgrastim (Neulasta®), pegylated interferon-α2a (Pegasys®) pegylated interferon-α2b (PEG-Intron®) purchased from the marketplace. The addition of the PEG moiety effectively doubles the molecular weight of the three products. This presents a significant challenge for the application of NMR techniques. Nevertheless, the results showed that high-resolution spectra could be recorded for two of the three products. Comparison of the spectra of the pegylated protein and the non-pegylated protein shows that the chemical modification did not alter the HOS of these proteins. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Controlled release of liraglutide using thermogelling polymers in treatment of diabetes

PubMed Central

Chen, Yipei; Li, Yuzhuo; Shen, Wenjia; Li, Kun; Yu, Lin; Chen, Qinghua; Ding, Jiandong

2016-01-01

In treatment of diabetes, it is much desired in clinics and challenging in pharmaceutics and material science to set up a long-acting drug delivery system. This study was aimed at constructing a new delivery system using thermogelling PEG/polyester copolymers. Liraglutide, a fatty acid-modified antidiabetic polypeptide, was selected as the model drug. The thermogelling polymers were presented by poly(ε-caprolactone-co-glycolic acid)-poly(ethylene glycol)-poly(ε-caprolactone-co-glycolic acid) (PCGA-PEG-PCGA) and poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA). Both the copolymers were soluble in water, and their concentrated solutions underwent temperature-induced sol-gel transitions. The drug-loaded polymer solutions were injectable at room temperature and gelled in situ at body temperature. Particularly, the liraglutide-loaded PCGA-PEG-PCGA thermogel formulation exhibited a sustained drug release manner over one week in both in vitro and in vivo tests. This feature was attributed to the combined effects of an appropriate drug/polymer interaction and a high chain mobility of the carrier polymer, which facilitated the sustained diffusion of drug out of the thermogel. Finally, a single subcutaneous injection of this formulation showed a remarkably improved glucose tolerance of mice for one week. Hence, the present study not only developed a promising long-acting antidiabetic formulation, but also put forward a combined strategy for controlled delivery of polypeptide. PMID:27531588

A dual-targeting nanocarrier based on poly(amidoamine) dendrimers conjugated with transferrin and tamoxifen for treating brain gliomas.

PubMed

Li, Yan; He, Hai; Jia, Xinru; Lu, Wan-Liang; Lou, Jinning; Wei, Yen

2012-05-01

A pH-sensitive dual-targeting drug carrier (G4-DOX-PEG-Tf-TAM) was synthesized with transferrin (Tf) conjugated on the exterior and Tamoxifen (TAM) in the interior of the fourth generation PAMAM dendrimers for enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. It was found that, on average, 7 doxorubicine (DOX) molecules, over 30 PEG(1000) and PEG(2000) chains and one Tf group were bonded on the periphery of each G4 PAMAM dendrimer, while 29 TAM molecules were encapsulated into the interior of per dendrimer. The pH-triggered DOX release was 32% at pH 4.5 and 6% at pH 7.4, indicating a comparatively fast drug release at weak acidic condition and stable state of the carrier at physiological environment. The in vitro assay of the drug transport across the BBB model showed that G4-DOX-PEG-Tf-TAM exhibited higher BBB transportation ability with the transporting ratio of 6.06% in 3 h. The carrier was internalized into C6 glioma cells upon crossing the BBB model by the coactions of TfR-mediated endocytosis and the inhibition effect of TAM to the drug efflux transports. Moreover, it also displayed the in vitro accumulation of DOX in the avascular C6 glioma spheroids made the tumor volume effectively reduced. Copyright © 2012 Elsevier Ltd. All rights reserved.

Multifunctional PEG-carboxylate copolymer coated superparamagnetic iron oxide nanoparticles for biomedical application

NASA Astrophysics Data System (ADS)

Illés, Erzsébet; Szekeres, Márta; Tóth, Ildikó Y.; Szabó, Ákos; Iván, Béla; Turcu, Rodica; Vékás, Ladislau; Zupkó, István; Jaics, György; Tombácz, Etelka

2018-04-01

Biocompatible magnetite nanoparticles (MNPs) were prepared by post-coating the magnetic nanocores with a synthetic polymer designed specifically to shield the particles from non-specific interaction with cells. Poly(ethylene glycol) methyl ether methacrylate (PEGMA) macromonomers and acrylic acid (AA) small molecular monomers were chemically coupled by quasi-living atom transfer radical polymerization (ATRP) to a comb-like copolymer, P(PEGMA-co-AA) designated here as P(PEGMA-AA). The polymer contains pendant carboxylate moieties near the backbone and PEG side chains. It is able to bind spontaneously to MNPs; stabilize the particles electrostatically via the carboxylate moieties and sterically via the PEG moieties; provide high protein repellency via the structured PEG layer; and anchor bioactive proteins via peptide bond formation with the free carboxylate groups. The presence of the P(PEGMA-AA) coating was verified in XPS experiments. The electrosteric (i.e., combined electrostatic and steric) stabilization is efficient down to pH 4 (at 10 mM ionic strength). Static magnetization and AC susceptibility measurements showed that the P(PEGMA-AA)@MNPs are superparamagnetic with a saturation magnetization value of 55 emu/g and that both single core nanoparticles and multicore structures are present in the samples. The multicore components make our product well suited for magnetic hyperthermia applications (SAR values up to 17.44 W/g). In vitro biocompatibility, cell internalization, and magnetic hyperthermia studies demonstrate the excellent theranostic potential of our product.

Keratocyte behavior in three-dimensional photopolymerizable poly(ethylene glycol) hydrogels

PubMed Central

Thibault, Richard; Ambrose, Winnette McIntosh; Schein, Oliver D.; Chakravarti, Shukti; Elisseeff, Jennifer

2015-01-01

The goal of this study was to evaluate three-dimensional (3-D) poly(ethylene glycol) (PEG) hydrogels as a culture system for studying corneal keratocytes. Bovine keratocytes were subcultured in DMEM/F-12 containing 10% fetal bovine serum (FBS) through passage 5. Primary keratocytes (P0) and corneal fibroblasts from passages 1 (P1) and 3 (P3) were photoencapsulated at various cell concentrations in PEG hydrogels via brief exposure to light. Additional hydrogels contained adhesive YRGDS and nonadhesive YRDGS peptides. Hydrogel constructs were cultured in DMEM/F-12 with 10% FBS for 2 and 4 weeks. Cell viability was assessed by DNA quantification and vital staining. Biglycan, type I collagen, type III collagen, keratocan and lumican expression were determined by reverse transcriptase–polymerase chain reaction. Deposition of type I collagen, type III collagen and keratan sulfate (KS)-containing matrix components was visualized using confocal microscopy. Keratocytes in a monolayer lost their stellate morphology and keratocan expression, displayed elongated cell bodies, and up-regulated biglycan, type I collagen and type III collagen characteristic of corneal fibroblasts. Encapsulated keratocytes remained viable for 4 weeks with spherical morphologies. Hydrogels supported production of KS, type I collagen and type III collagen matrix components. PEG-based hydrogels can support keratocyte viability and matrix production. 3-D hydrogel culture can stabilize but not restore the keratocyte phenotype. This novel application of PEG hydrogels has potential use in the study of corneal keratocytes in a 3-D environment. PMID:18567550

Partial purification of penicillin acylase from Escherichia coli in poly(ethylene glycol)-sodium citrate aqueous two-phase systems.

PubMed

Marcos, J C; Fonseca, L P; Ramalho, M T; Cabral, J M

1999-10-29

Studies on the partition and purification of penicillin acylase from Escherichia coli osmotic shock extract were performed in poly(ethylene glycol)-sodium citrate systems. Partition coefficient behavior of the enzyme and total protein are similar to those described in other reports, increasing with pH and tie line length and decreasing with PEG molecular weight. However, some selectivity could be attained with PEG 1000 systems and long tie line at pH 6.9. Under these conditions 2.6-fold purification with 83% yield were achieved. Influence of pH on partition shows that is the composition of the system and not the net charge of the enzyme that determines the behaviour in these conditions. Addition of NaCl to PEG 3350 systems significantly increases the partition of the enzyme. Although protein partition also increased, purification conditions were possible with 1.5 M NaCl where 5.7-fold purification and 85% yield was obtained. This was possible due to the higher hydrophobicity of the enzyme compared to that of most contaminants proteins.

Tunnel current across linear homocatenated germanium chains

NASA Astrophysics Data System (ADS)

Matsuura, Yukihito

2014-01-01

The electronic transport properties of germanium oligomers catenating into linear chains (linear Ge chains) have been theoretically studied using first principle methods. The conduction mechanism of a Ge chain sandwiched between gold electrodes was analyzed based on the density of states and the eigenstates of the molecule in a two-probe environment. Like that of silicon chains (Si chains), the highest occupied molecular orbital of Ge chains contains the extended σ-conjugation of Ge 4p orbitals at energy levels close to the Fermi level; this is in contrast to the electronic properties of linear carbon chains. Furthermore, the conductance of a Ge chain is expected to decrease exponentially with molecular length L. The decay constant β, which is defined as e-βL, of a Ge chain is similar to that of a Si chain, whereas the conductance of the Ge chains is higher than that of Si chains even though the Ge-Ge bond length is longer than the Si-Si bond length.

Characterization of Hydrophobic Interactions of Polymers with Water and Phospholipid Membranes Using Molecular Dynamics Simulations

NASA Astrophysics Data System (ADS)

Drenscko, Mihaela

Polymers and lipid membranes are both essential soft materials. The structure and hydrophobicity/hydrophilicity of polymers, as well as the solvent they are embedded in, ultimately determines their size and shape. Understating the variation of shape of the polymer as well as its interactions with model biological membranes can assist in understanding the biocompatibility of the polymer itself. Computer simulations, in particular molecular dynamics, can aid in characterization of the interaction of polymers with solvent, as well as polymers with model membranes. In this thesis, molecular dynamics serve to describe polymer interactions with a solvent (water) and with a lipid membrane. To begin with, we characterize the hydrophobic collapse of single polystyrene chains in water using molecular dynamics simulations. Specifically, we calculate the potential of mean force for the collapse of a single polystyrene chain in water using metadynamics, comparing the results between all atomistic with coarse-grained molecular simulation. We next explore the scaling behavior of the collapsed globular shape at the minimum energy configuration, characterized by the radius of gyration, as a function of chain length. The exponent is close to one third, consistent with that predicted for a polymer chain in bad solvent. We also explore the scaling behavior of the Solvent Accessible Surface Area (SASA) as a function of chain length, finding a similar exponent for both all-atomistic and coarse-grained simulations. Furthermore, calculation of the local water density as a function of chain length near the minimum energy configuration suggests that intermediate chain lengths are more likely to form dewetted states, as compared to shorter or longer chain lengths. Next, in order to investigate the molecular interactions between single hydrophobic polymer chains and lipids in biological membranes and at lipid membrane/solvent interface, we perform a series of molecular dynamics simulations of small membranes using all atomistic and coarse-grained methods. The molecular interaction between common polymer chains used in biomedical applications and the cell membrane is unknown. This interaction may affect the biocompatibility of the polymer chains. Molecular dynamics simulations offer an emerging tool to characterize the interaction between common degradable polymer chains used in biomedical applications, such as polycaprolactone, and model cell membranes. We systematically characterize with long-time all-atomistic molecular dynamics simulations the interaction between single polycaprolactone chains of varying chain lengths with a model phospholipid membrane. We find that the length of polymer chain greatly affects the nature of interaction with the membrane, as well as the membrane properties. Furthermore, we next utilize advanced sampling techniques in molecular dynamics to characterize the two-dimensional free energy surface for the interaction of varying polymer chain lengths (short, intermediate, and long) with model cell membranes. We find that the free energy minimum shifts from the membrane-water interface to the hydrophobic core of the phospholipid membrane as a function of chain length. These results can be used to design polymer chain lengths and chemistries to optimize their interaction with cell membranes at the molecular level.

A randomized controlled study to establish the effect of articulating instruments on performance in single-incision laparoscopic surgery.

PubMed

Corker, Harry P; Singh, Pritam; Sodergren, Mikael H; Balaji, Sathyan; Kwasnicki, Richard M; Darzi, Ara W; Paraskeva, Paraskevas

2015-01-01

In single-incision laparoscopic surgery (SILS), operating through 1 incision presents ergonomic challenges. No consensus exists on whether articulating instruments (ARTs) may help. This study evaluated their effect on simulated SILS, hypothesizing that they would affect performance and workload. Surgeons were randomized to 2 straight instruments (STRs), 1 ART and 1 STR, or 2 ARTs. After baseline testing, 25 repetitions of the Fundamentals of Laparoscopic Surgery (FLS) peg-transfer (PEG) task and 5 repetitions of the short-hand for the FLS pattern-cutting task (CIRCLE) were performed. Primary outcomes were maximum FLS PEG scores, CIRCLE times and errors, and Imperial College Surgical Assessment Device hand motion analysis. National Aeronautics and Space Administration (NASA) Raw Task Load Index (RTLX) questionnaires evaluated a secondary outcome--workload. The trial took place in a simulated operating theater within the Academic Surgical Unit at St Mary's Hospital, London, UK. Eligible surgeons had completed at least 5 laparoscopic cases as a primary operator. Surgeons were stratified by laparoscopic experience into intermediate (less than 25 previous procedures as primary operator) or advanced (25 procedures or more). A total of 21 surgeons were recruited and randomized; 7 of them to each instrument combination group. All surgeons completed PEG, and 5 from each group completed CIRCLE. Groups' baseline PEG scores were similar (p = 0.625). STR-ART achieved higher maximum PEG scores than STR or ART did (median = 236 vs 198 vs 193, respectively, p = 0.002). Fastest CIRCLE times were similar (median = 190s vs 130s vs 186s, p = 0.129) as were minimum errors (median = 1 vs 2 vs 3, p = 0.101). For PEG, Imperial College Surgical Assessment Device demonstrated similar total path lengths (median = 12.3m vs 12.3m vs 16.0m, p = 0.545) and total numbers of movements (median = 89.6 vs 86.4 vs 171, p = 0.080). Groups' NASA Raw Task Load Index scores were similar (p = 0.708). Combining 1 STR and 1 ART improved SILS performance in the PEG task. Therefore, this may be the optimum instrument configuration for use within some clinical SILS applications. Copyright © 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Lactulose vs Polyethylene Glycol 3350-Electrolyte Solution for Treatment of Overt Hepatic Encephalopathy

PubMed Central

Rahimi, Robert S.; Singal, Amit G.; Cuthbert, Jennifer A.; Rockey, Don C.

2017-01-01

IMPORTANCE Hepatic encephalopathy (HE) is a common cause of hospitalization in patients with cirrhosis. Pharmacologic treatment for acute (overt) HE has remained the same for decades. OBJECTIVE To compare polyethylene glycol 3350–electrolyte solution (PEG) and lactulose treatments in patients with cirrhosis admitted to the hospital for HE. We hypothesized that rapid catharsis of the gut using PEG may resolve HE more effectively than lactulose. DESIGN, SETTING, AND PARTICIPANTS The HELP (Hepatic Encephalopathy: Lactulose vs Polyethylene Glycol 3350-Electrolyte Solution) study is a randomized clinical trial in an academic tertiary hospital of 50 patients with cirrhosis (of 186 screened) admitted for HE. INTERVENTIONS Participants were block randomized to receive treatment with PEG, 4-L dose (n = 25), or standard-of-care lactulose (n = 25) during hospitalization. MAIN OUTCOMES AND MEASURES The primary end point was an improvement of 1 or more in HE grade at 24 hours, determined using the hepatic encephalopathy scoring algorithm (HESA), ranging from 0 (normal clinical and neuropsychological assessments) to 4 (coma). Secondary outcomes included time to HE resolution and overall length of stay. RESULTS A total of 25 patients were randomized to each treatment arm. Baseline clinical features at admission were similar in the groups. Thirteen of 25 patients in the standard therapy arm (52%) had an improvement of 1 or more in HESA score, thus meeting the primary outcome measure, compared with 21 of 23 evaluated patients receiving PEG (91%) (P < .01); 1 patient was discharged before final analysis and 1 refused participation. The mean (SD) HESA score at 24 hours for patients receiving standard therapy changed from 2.3 (0.9) to 1.6 (0.9) compared with a change from 2.3 (0.9) to 0.9 (1.0) for the PEG-treated groups (P = .002). The median time for HE resolution was 2 days for standard therapy and 1 day for PEG (P = .01). Adverse events were uncommon, and none was definitely study related. CONCLUSIONS AND RELEVANCE PEG led to more rapid HE resolution than standard therapy, suggesting that PEG may be superior to standard lactulose therapy in patients with cirrhosis hospitalized for acute HE. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01283152 PMID:25243839

Quantum communication beyond the localization length in disordered spin chains.

PubMed

Allcock, Jonathan; Linden, Noah

2009-03-20

We study the effects of localization on quantum state transfer in spin chains. We show how to use quantum error correction and multiple parallel spin chains to send a qubit with high fidelity over arbitrary distances, in particular, distances much greater than the localization length of the chain.

Crossover transition in flowing granular chains

NASA Astrophysics Data System (ADS)

Ulrich, Xialing; Fried, Eliot; Shen, Amy Q.

2009-09-01

We report on the dynamical and statistical behavior of flowing collections of granular chains confined two-dimensionally (2D) within a rotating tumbler. Experiments are conducted with systems of chains of fixed length, but various lengths are considered. The dynamics are punctuated by cascades of chains along a free-surface cascades, which drive the development of mixed porous/laminar packing arrangements in bulk. We investigate the conformation of the system, as characterized by the porosity of the flow region occupied by the chains and the mean-square end-to-end distance of the chains during flow. Both of these measures show crossover transitions from a 2D self-avoiding walk to a 2D random walk when the chain length becomes long enough to allow self-contact.

Structure-guided investigation of lipopolysaccharide O-antigen chain length regulators reveals regions critical for modal length control.

PubMed

Kalynych, Sergei; Ruan, Xiang; Valvano, Miguel A; Cygler, Miroslaw

2011-08-01

The O-antigen component of the lipopolysaccharide (LPS) represents a population of polysaccharide molecules with nonrandom (modal) chain length distribution. The number of the repeat O units in each individual O-antigen polymer depends on the Wzz chain length regulator, an inner membrane protein belonging to the polysaccharide copolymerase (PCP) family. Different Wzz proteins confer vastly different ranges of modal lengths (4 to >100 repeat units), despite having remarkably conserved structural folds. The molecular mechanism responsible for the selective preference for a certain number of O units is unknown. Guided by the three-dimensional structures of PCPs, we constructed a panel of chimeric molecules containing parts of two closely related Wzz proteins from Salmonella enterica and Shigella flexneri which confer different O-antigen chain length distributions. Analysis of the O-antigen length distribution imparted by each chimera revealed the region spanning amino acids 67 to 95 (region 67 to 95), region 200 to 255, and region 269 to 274 as primarily affecting the length distribution. We also showed that there is no synergy between these regions. In particular, region 269 to 274 also influenced chain length distribution mediated by two distantly related PCPs, WzzB and FepE. Furthermore, from the 3 regions uncovered in this study, region 269 to 274 appeared to be critical for the stability of the oligomeric form of Wzz, as determined by cross-linking experiments. Together, our data suggest that chain length determination depends on regions that likely contribute to stabilize a supramolecular complex.

Majorana bound states in the finite-length chain

NASA Astrophysics Data System (ADS)

Zvyagin, A. A.

2015-08-01

Recent experiments investigating edge states in ferromagnetic atomic chains on superconducting substrate are analyzed. In particular, finite size effects are considered. It is shown how the energy of the Majorana bound state depends on the length of the chain, as well as on the parameters of the model. Oscillations of the energy of the bound edge state in the chain as a function of the length of the chain, and as a function of the applied voltage (or the chemical potential) are studied. In particular, it has been shown that oscillations can exist only for some values of the effective potential.

Antioxidative effect of lipophilized caffeic acid in fish oil enriched mayonnaise and milk.

PubMed

Alemán, Mercedes; Bou, Ricard; Guardiola, Francesc; Durand, Erwann; Villeneuve, Pierre; Jacobsen, Charlotte; Sørensen, Ann-Dorit Moltke

2015-01-15

The antioxidative effect of lipophilized caffeic acid was assessed in two different fish oil enriched food products: mayonnaise and milk. In both emulsion systems, caffeic acid esterified with fatty alcohols of different chain lengths (C1-C20) were better antioxidants than the original phenolic compound. The optimal chain length with respect to protection against oxidation was, however, different for the two food systems. Fish oil enriched mayonnaise with caffeates of medium alkyl chain length (butyl, octyl and dodecyl) added resulted in a better oxidative stability than caffeates with shorter (methyl) or longer (octadecyl) alkyl chains. Whereas in fish oil enriched milk emulsions the most effective caffeates were those with shorter alkyl chains (methyl and butyl) rather than the ones with medium and long chains (octyl, dodecyl, hexadecyl and eicosyl). These results demonstrate that there might be an optimum alkyl chain length for each phenolipid in each type of emulsion systems. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effect of carbon chain length of starting materials on the formation of carbon dots and their optical properties

NASA Astrophysics Data System (ADS)

Pan, Xiaohua; Zhang, Yan; Sun, Xiaobo; Pan, Wei; Yu, Guifeng; Si, Shuxin; Wang, Jinping

2018-04-01

Carbon dots (CDs) have attracted increasing attention due to their high performances and potential applications in wide range of areas. However, their emission mechanism is not clear so far. In order to reveal more factors contributing to the emission of CDs, the effect of carbon chain length of starting materials on the formation of CDs and their optical properties was experimentally investigated in this work. In order to focus on the effect of carbon chain length, the starting materials with C, O, N in fully identical forms and only carbon chain lengths being different were selected for synthesizing CDs, including citric acid (CA) and adipic acid (AA) as carbon sources, and diamines with different carbon chain lengths (H2N(CH2)nNH2, n = 2, 4, 6) as nitrogen sources, as well as ethylenediamine (EDA) as nitrogen source and diacids with different carbon chain lengths (HOOC(CH2)nCOOH, n = 0, 2, 4, 6) as carbon sources. Therefore, the effect of carbon chain length of starting materials on the formation and optical properties of CDs can be systematically investigated by characterizing and comparing the structures and optical properties of as-prepared nine types of CDs. Moreover, the density of –NH2 on the surface of the CDs was quantitatively detected by a spectrophotometry so as to elucidate the relationship between the –NH2 related surface state and the optical properties.

Enhancing the specificity of polymerase chain reaction by graphene oxide through surface modification: zwitterionic polymer is superior to other polymers with different charges.

PubMed

Zhong, Yong; Huang, Lihong; Zhang, Zhisen; Xiong, Yunjing; Sun, Liping; Weng, Jian

Graphene oxides (GOs) with different surface characteristics, such as size, reduction degree and charge, are prepared, and their effects on the specificity of polymerase chain reaction (PCR) are investigated. In this study, we demonstrate that GO with a large size and high reduction degree is superior to small and nonreduced GO in enhancing the specificity of PCR. Negatively charged polyacrylic acid (PAA), positively charged polyacrylamide (PAM), neutral polyethylene glycol (PEG) and zwitterionic polymer poly(sulfobetaine) (pSB) are used to modify GO. The PCR specificity-enhancing ability increases in the following order: GO-PAA < GO-PAM < GO-PEG < GO-pSB. Thus, zwitterionic polymer-modified GO is superior to other GO derivatives with different charges in enhancing the specificity of PCR. GO derivatives are also successfully used to enhance the specificity of PCR for the amplification of human mitochondrial DNA using blood genomic DNA as template. Molecular dynamics simulations and molecular docking are performed to elucidate the interaction between the polymers and Pfu DNA polymerase. Our data demonstrate that the size, reduction degree and surface charge of GO affect the specificity of PCR. Based on our results, zwitterionic polymer-modified GO may be used as an efficient additive for enhancing the specificity of PCR.

Unit and internal chain profile of African rice (Oryza glaberrima) amylopectin.

PubMed

Gayin, Joseph; Abdel-Aal, El-Sayed M; Manful, John; Bertoft, Eric

2016-02-10

High-performance anion-exchange chromatography was used to study the unit chain profiles of amylopectins and their φ,β-limit dextrins from two African rice (Oryza glaberrima) accessions-TOG 12440 and IRGC 103759. The samples were compared with two Asian rice (Oryza sativa) samples (cv Koshihikari and cv WITA 4) and one O. sativa × O. glaberrima cross (NERICA 4). The ratio of short:long chains ranged between 12.1 and 13.8, and the ratio of A:B-chains was ∼ 1.0 in all samples. A significant difference was observed in the distribution of internal chains with regards to the proportion of short "fingerprint" B-chains (Bfp-chains), which in the φ,β-limit dextrins have a degree of polymerization (DP) 3-7. The African rice starches and NERICA 4 had higher levels of Bfp-chains, but the major group of short B-chains (DP 8-25) was similar to that of the Asian rice samples. The average chain length (CL), internal chain length (ICL), and total internal chain length (TICL) were similar in all samples. However, the external chain length (ECL) was longer in the African rice samples and NERICA 4. ECL correlated positively and significantly (p<0.05) with gelatinization transition temperatures and enthalpy suggesting differences between the two rice types in cooking properties. Copyright © 2015 Elsevier Ltd. All rights reserved.

Wheat TaSP gene improves salt tolerance in transgenic Arabidopsis thaliana.

PubMed

Ma, Xiaoli; Cui, Weina; Liang, Wenji; Huang, Zhanjing

2015-12-01

A novel salt-induced gene with unknown functions was cloned through analysis of gene expression profile of a salt-tolerant wheat mutant RH8706-49 under salt stress. The gene was named Triticum aestivum salt-related protein (TaSP) and deposited in GenBank (Accession No. KF307326). Quantitative polymerase chain reaction (qPCR) results showed that TaSP expression was induced under salt, abscisic acid (ABA), and polyethylene glycol (PEG) stresses. Subcellular localization revealed that TaSP was mainly localized in cell membrane. Overexpression of TaSP in Arabidopsis could improve salt tolerance of 35S::TaSP transgenic Arabidopsis. 35S::TaSP transgenic Arabidopsis lines after salt stress presented better physiological indexes than the control group. In the non-invasive micro-test (NMT), an evident Na(+) excretion was observed at the root tip of salt-stressed 35S::TaSP transgenic Arabidopsis. TaSP promoter was cloned, and its beta-glucuronidase (GUS) activities before and after ABA, salt, cold, heat, and salicylic acid (SA) stresses were determined. Full-length TaSP promoter contained ABA and salt response elements. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Nanopore analysis of polymers in solution.

NASA Astrophysics Data System (ADS)

Deamer, David

2002-03-01

Nanopores represent a novel approach for investigating macromolecules in solution. Polymers that have been analyzed by this technique include polyethylene glycol (PEG), certain proteins and nucleic acids. The a-hemolysin pore inserted into lipid bilayers provides continuous non-gated ion current through a pore diameter of approximately 1.5 - 2 nm. Nucleic acid molecules can be driven through the pore by imposing a voltage across the supporting membrane. Single stranded, but not double stranded nucleic acids pass through in strict linear sequence from one end of the molecule to the other. While in the pore, the molecule reduces ionic current, and properties of the ionic current blockade such as duration, mean amplitude and modulations of amplitude provide information about structure and composition of the nucleic acid. For a given molecular species, the duration of the blockade is a function of chain length, and the rate of blockades is linearly related to concentration. More recent studies have shown that the a-hemolysin nanopore can discriminate between synthetic DNA molecules differing by a single base pair or even a single nucleotide. These results indicate that a nanopore may have the resolution required for nucleic acid sequencing applications.

[Construction of dengue virus-specific full-length fully human antibody libraries by mammalian display technology].

PubMed

Wen, Yangming; Lan, Kaijian; Wang, Junjie; Yu, Jingyi; Qu, Yarong; Zhao, Wei; Zhang, Fuchun; Tan, Wanlong; Cao, Hong; Zhou, Chen

2013-06-01

To construct dengue virus-specific full-length fully human antibody libraries using mammalian cell surface display technique. Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) from convalescent patients with dengue fever. The reservoirs of the light chain and heavy chain variable regions (LCκ and VH) of the antibody genes were amplified by RT-PCR and inserted into the vector pDGB-HC-TM separately to construct the light chain and heavy chain libraries. The library DNAs were transfected into CHO cells and the expression of full-length fully human antibodies on the surface of CHO cells was analyzed by flow cytometry. Using 1.2 µg of the total RNA isolated from the PBMCs as the template, the LCκ and VH were amplified and the full-length fully human antibody mammalian display libraries were constructed. The kappa light chain gene library had a size of 1.45×10(4) and the heavy chain gene library had a size of 1.8×10(5). Sequence analysis showed that 8 out of the 10 light chain clones and 7 out of the 10 heavy chain clones randomly picked up from the constructed libraries contained correct open reading frames. FACS analysis demonstrated that all the 15 clones with correct open reading frames expressed full-length antibodies, which could be detected on CHO cell surfaces. After co-transfection of the heavy chain and light chain gene libraries into CHO cells, the expression of full-length antibodies on CHO cell surfaces could be detected by FACS analysis with an expressible diversity of the antibody library reaching 1.46×10(9) [(1.45×10(4)×80%)×(1.8×10(5)×70%)]. Using 1.2 µg of total RNA as template, the LCκ and VH full-length fully human antibody libraries against dengue virus have been successfully constructed with an expressible diversity of 10(9).

Understanding the effect of alkyl chains of gemini cations on the physicochemical and cellular properties of polyurethane micelles.

PubMed

Pan, Zhicheng; Fang, Danxuan; Song, Yuanqing; Song, Nijia; Ding, Mingming; Li, Jiehua; Luo, Feng; Li, Jianshu; Tan, Hong; Fu, Qiang

2018-06-06

Cationic gemini quaternary ammonium (GQA) has been used as a cell internalization promoter to improve the permeability of the cell membrane and enhance the cellular uptake. However, the effect of the alkyl chain length on the cellular properties of nanocarriers has not been elucidated yet. In this study, we developed a series of polyurethane micelles containing GQAs with various alkyl chain lengths. The alteration of the gemini alkyl chain length was found to change the distribution of GQA surfactants in the micellar structure and affect the surface charge exposure, stability, and the protein absorption properties of nanocarriers. Moreover, we also clarified the role of the alkyl chain length in tumor cell internalization and macrophage uptake of polyurethane micelles. This work provides a new understanding on the effect of the GQA alkyl chain length on the physicochemical and biological properties of nanomedicines, and offers guidance on the rational design of effective drug delivery systems where the issue of functional group exposure at the micellar surface should be considered.

Structure and Dynamics of Polymer/Polymer grafted nanoparticle composite

NASA Astrophysics Data System (ADS)

Archer, Lynden

Addition of nanoparticles to polymers is a well-practiced methodology for augmenting various properties of the polymer host, including mechanical strength, thermal stability, barrier properties, dimensional stability and wear resistance. Many of these property changes are known to arise from nanoparticle-induced modification of polymer structure and chain dynamics, which are strong functions of the dispersion state of the nanoparticles' and on their relative size (D) to polymer chain dimensions (e.g. Random coil radius Rg or entanglement mesh size a) . This talk will discuss polymer nanocomposites (PNCs) comprised of Polyethylene Glycol (PEG) tethered silica nanoparticles (SiO2-PEG) dispersed in polymers as model systems for investigating phase stability and dynamics of PNCs. On the basis of small-angle X-ray Scattering, it will be shown that favorable enthalpic interactions between particle-tethered chains and a polymer host provides an important mechanism for creating PNCs in which particle aggregation is avoided. The talk will report on polymer and particle scale dynamics in these materials and will show that grafted nanoparticles well dispersed in a polymer host strongly influence the host polymer relaxation dynamics on all timescales and the polymers in turn produce dramatic changes in the nature (from diffusive to hyperdiffusive) and speed of nano particle decorrelation dynamics at the polymer entanglement threshold. A local viscosity model capable of explaining these observations is discussed and the results compared with scaling theories for NP motions in polymers This material is based on work supported by the National Science Foundation Award Nos. DMR-1609125 and CBET-1512297.

Structure of gel phase saturated lecithin bilayers: temperature and chain length dependence.

PubMed Central

Sun, W J; Tristram-Nagle, S; Suter, R M; Nagle, J F

1996-01-01

Systematic low-angle and wide-angle x-ray scattering studies have been performed on fully hydrated unoriented multilamamellar vesicles of saturated lecithins with even chain lengths N = 16, 18, 20, 22, and 24 as a function of temperature T in the normal gel (L beta') phase. For all N, the area per chain Ac increases linearly with T with an average slope dAc/dT = 0.027 A2/degree C, and the lamellar D-spacings also increase linearly with an average slope dD/dT = 0.040 A/degree C. At the same T, longer chain length lecithins have more densely packed chains, i.e., smaller Ac's, than shorter chain lengths. The chain packing of longer chain lengths is found to be more distorted from hexagonal packing than that of smaller N, and the distortion epsilon of all N approaches the same value at the respective transition temperatures. The thermal volume expansion of these lipids is accounted for by the expansion in the hydrocarbon chain region. Electron density profiles are constructed using four orders of low-angle lamellar peaks. These show that most of the increase in D with increasing T is due to thickening of the bilayers that is consistent with a decrease in tilt angle theta and with little change in water spacing with either T or N. Because of the opposing effects of temperature on area per chain Ac and tilt angle 0, the area expansivity alpha A is quite small. A qualitative theoretical model based on competing head and chain interactions accounts for our results. PMID:8842227

Mussel-Inspired Dopamine and Carbon Nanotube Leading to a Biocompatible Self-Rolling Conductive Hydrogel Film.

PubMed

Jiang, Junzi; Huang, Yong; Wang, Yitian; Xu, Hui; Xing, Malcolm; Zhong, Wen

2017-08-18

We report a novel self-rolling, conductive, and biocompatible multiwall carbon nanotube (MWCNT)-dopamine-polyethylene glycol (PEG) hydrogel film. The gel can self-fold into a thin tube when it is transferred from a glass slide to an aqueous environment, regardless of the concentrations of the MWCNT. The film presents a highly organized pattern, which results from the self-assembly of hydrophilic dopamine and hydrophobic carbon nanotubes. By exploring the biomedical potential, we found that MWCNT-included rolled film is nontoxic and can promote cell growth. For further functional verification by qPCR (quantitative polymerase chain reaction), bone marrow derived mesenchymal cells present higher levels of osteogenic differentiations in response to a higher concentration of CNTs. The results suggest that the self-rolling, conductive CNT-dopamine-PEG hydrogel could have multiple potentials, including biomedical usage and as a conductive biosensor.

Microcellular foaming of arabinoxylan and PEGylated arabinoxylan with supercritical CO2.

PubMed

Härdelin, Linda; Ström, Anna; Di Maio, Ernesto; Iannace, Salvatore; Larsson, Anette

2018-02-01

In this study, arabinoxylan extracted from barley husks was reacted with polyethylene glycol (PEG) of various molecular weights to introduce an internal plasticizer into the polymer matrix. A successful PEGylation reaction was identified using FTIR and elemental analysis. Thermal and mechanical properties were studied using dynamic mechanical analysis, which revealed that the attachment of PEG chains reduced the glass transition temperature by up to 25°C. Foaming experiments were conducted under different test conditions in a batch foaming process with supercritical CO 2 in a thermoregulated and pressurized cylinder. The foams were evaluated using SEM by studying the morphology of the samples foamed at different temperatures. The unmodified arabinoxylan sample was found to produce the best foam morphology, though the PEGylated samples could be produced at lower temperatures than could the unmodified arabinoxylan. This was interpreted as due to the decrease in the glass transition temperature. Copyright © 2017. Published by Elsevier Ltd.

Biosynthesis of medium chain length alkanes for bio-aviation fuel by metabolic engineered Escherichia coli.

PubMed

Wang, Meng; Nie, Kaili; Cao, Hao; Xu, Haijun; Fang, Yunming; Tan, Tianwei; Baeyens, Jan; Liu, Luo

2017-09-01

The aim of this work was to study the synthesis of medium-chain length alkanes (MCLA), as bio-aviation product. To control the chain length of alkanes and increase the production of MCLA, Escherichia coli cells were engineered by incorporating (i) a chain length specific thioesterase from Umbellularia californica (UC), (ii) a plant origin acyl carrier protein (ACP) gene and (iii) the whole fatty acid synthesis system (FASs) from Jatropha curcas (JC). The genetic combination was designed to control the product spectrum towards optimum MCLA. Decanoic, lauric and myristic acid were produced at concentrations of 0.011, 0.093 and 1.657mg/g, respectively. The concentration of final products nonane, undecane and tridecane were 0.00062mg/g, 0.0052mg/g, and 0.249mg/g respectively. Thioesterase from UC controlled the fatty acid chain length in a range of 10-14 carbons and the ACP gene with whole FASs from JC significantly increased the production of MCLA. Copyright © 2017 Elsevier Ltd. All rights reserved.

Characterization of amylose nanoparticles prepared via nanoprecipitation: Influence of chain length distribution.

PubMed

Chang, Yanjiao; Yang, Jingde; Ren, Lili; Zhou, Jiang

2018-08-15

The influence of chain length distribution of amylose on size and structure of the amylose nanoparticles (ANPs) prepared through nanoprecipitation was investigated. Amylose with different chain length distributions was obtained by β-amylase treating amylose paste for different times and measured by size exclusion chromatography (SEC) and fluorophore-assisted carbohydrate electrophoresis (FACE). ANPs prepared via precipitation were characterized by using dynamic light scattering (DLS), scanning electron microscopy (SEM) and X-ray diffraction (XRD). Results showed that the β-amylase treatments led to decrease in chain length of amylose, and it was the most important factor affecting size of ANPs. When hydrolysis degree of amylose was 52.8%, mean size of ANPs decreased from 206.4 nm to 102.7 nm. All the ANPs displayed a V-type crystalline structure and the effect of amylose chain length on crystallinity of the precipitated ANPs was negligible in the investigated range. Copyright © 2018 Elsevier Ltd. All rights reserved.

Exploring the impact of the side-chain length on peptide/RNA binding events.

PubMed

Sbicca, Lola; González, Alejandro López; Gresika, Alexandra; Di Giorgio, Audrey; Closa, Jordi Teixido; Tejedor, Roger Estrada; Andréola, Marie-Line; Azoulay, Stéphane; Patino, Nadia

2017-07-19

The impact of the amino-acid side-chain length on peptide-RNA binding events has been investigated using HIV-1 Tat derived peptides as ligands and the HIV-1 TAR RNA element as an RNA model. Our studies demonstrate that increasing the length of all peptide side-chains improves unexpectedly the binding affinity (K D ) but reduces the degree of compactness of the peptide-RNA complex. Overall, the side-chain length appears to modulate in an unpredictable way the ability of the peptide to compete with the cognate TAR RNA partner. Beyond the establishment of non-intuitive fundamental relationships, our results open up new perspectives in the design of effective RNA ligand competitors, since a large number of them have already been identified but few studies report on the modulation of the biological activity by modifying in the same way the length of all chains connecting RNA recognition motives to the central scaffold of a ligand.

Design of ligand-targeted nanoparticles for enhanced cancer targeting

NASA Astrophysics Data System (ADS)

Stefanick, Jared F.

Ligand-targeted nanoparticles are increasingly used as drug delivery vehicles for cancer therapy, yet have not consistently produced successful clinical outcomes. Although these inconsistencies may arise from differences in disease models and target receptors, nanoparticle design parameters can significantly influence therapeutic efficacy. By employing a multifaceted synthetic strategy to prepare peptide-targeted nanoparticles with high purity, reproducibility, and precisely controlled stoichiometry of functionalities, this work evaluates the roles of polyethylene glycol (PEG) coating, ethylene glycol (EG) peptide-linker length, peptide hydrophilicity, peptide density, and nanoparticle size on tumor targeting in a systematic manner. These parameters were analyzed in multiple disease models by targeting human epidermal growth factor receptor 2 (HER2) in breast cancer and very late antigen-4 (VLA-4) in multiple myeloma to demonstrate the widespread applicability of this approach. By increasing the hydrophilicity of the targeting peptide sequence and simultaneously optimizing the EG peptide-linker length, the in vitro cellular uptake of targeted liposomes was significantly enhanced. Specifically, including a short oligolysine chain adjacent to the targeting peptide sequence effectively increased cellular uptake ~80-fold using an EG6 peptide-linker compared to ~10-fold using an EG45 linker. In vivo, targeted liposomes prepared in a traditional manner lacking the oligolysine chain demonstrated similar biodistribution and tumor uptake to non-targeted liposomes. However, by including the oligolysine chain, targeted liposomes using an EG45 linker significantly improved tumor uptake ~8-fold over non-targeted liposomes, while the use of an EG6 linker decreased tumor accumulation and uptake, owing to differences in cellular uptake kinetics, clearance mechanisms, and binding site barrier effects. To further improve tumor targeting and enhance the selectivity of targeted nanoparticles, a dual-receptor targeted approach was evaluated by targeting multiple cell surface receptors simultaneously. Liposomes functionalized with two distinct peptide antagonists to target VLA-4 and Leukocyte Peyer's Patch Adhesion Molecule-1 (LPAM-1) demonstrated synergistically enhanced cellular uptake by cells overexpressing both target receptors and negligible uptake by cells that do not simultaneously express both receptors, providing a strategy to improve selectivity over conventional single receptor-targeted designs. Taken together, this process of systematic optimization of well-defined nanoparticle drug delivery systems has the potential to improve cancer therapy for a broader patient population.

Flexible chain molecules in the marginal and concentrated regimes: universal static scaling laws and cross-over predictions.

PubMed

Laso, Manuel; Karayiannis, Nikos Ch

2008-05-07

We present predictions for the static scaling exponents and for the cross-over polymer volumetric fractions in the marginal and concentrated solution regimes. Corrections for finite chain length are made. Predictions are based on an analysis of correlated fluctuations in density and chain length, in a semigrand ensemble in which mers and solvent sites exchange identities. Cross-over volumetric fractions are found to be chain length independent to first order, although reciprocal-N corrections are also estimated. Predicted scaling exponents and cross-over regimes are compared with available data from extensive off-lattice Monte Carlo simulations [Karayiannis and Laso, Phys. Rev. Lett. 100, 050602 (2008)] on freely jointed, hard-sphere chains of average lengths from N=12-500 and at packing densities from dilute ones up to the maximally random jammed state.

n-Alkane adsorption to polar silica surfaces.

PubMed

Brindza, Michael R; Ding, Feng; Fourkas, John T; Walker, Robert A

2010-03-21

The structures of medium-length n-alkane species (C(8)-C(11)) adsorbed to a hydrophilic silica/vapor interface were examined using vibrational sum frequency spectroscopy. Experiments sampling out-of-plane orientation show a clear pattern in vibrational band intensities that implies chains having primarily all-trans conformations lying flat along the interface. Further analysis shows that the methylene groups of the alkane chains have their local symmetry axes directed into and away from the surface. Spectra acquired under different polarization conditions interlock to reinforce this picture of interfacial structure and organization. Variation in signal intensities with chain length suggests that correlation between adsorbed monomers weakens with increasing chain length. This result stands in contrast with alkane behavior at neat liquid/vapor interfaces where longer length alkanes show considerably more surface induced ordering than short chain alkanes.

Ligand Assisted Stabilization of Fluorescence Nanoparticles; an Insight on the Fluorescence Characteristics, Dispersion Stability and DNA Loading Efficiency of Nanoparticles.

PubMed

Rhouati, Amina; Hayat, Akhtar; Mishra, Rupesh K; Bueno, Diana; Shahid, Shakir Ahmad; Muñoz, Roberto; Marty, Jean Louis

2016-07-01

This work reports on the ligand assisted stabilization of Fluospheres® carboxylate modified nanoparticles (FCMNPs), and subsequently investigation on the DNA loading capacity and fluorescence response of the modified particles. The designed fluorescence bioconjugate was characterized with enhanced fluorescence characteristics, good stability and large surface area with high DNA loading efficiency. For comparison purpose, bovine serum albumin (BSA) and polyethylene glycol (PEG) with three different length strands were used as cross linkers to modify the particles, and their DNA loading capacity and fluorescence characteristics were investigated. By comparing the performance of the particles, we found that the most improved fluorescence characteristics, enhanced DNA loading and high dispersion stability were obtained, when employing PEG of long spacer arm length. The designed fluorescence bioconjugate was observed to maintain all its characteristics under varying pH over an extended period of time. These types of bioconjugates are in great demand for fluorescence imaging and in vivo fluorescence biomedical application, especially when most of the as synthesized fluorescence particles cannot withstand to varying in vivo physiological conditions with decreases in fluorescence response and DNA loading efficiency.

Excess entropy scaling for the segmental and global dynamics of polyethylene melts.

PubMed

Voyiatzis, Evangelos; Müller-Plathe, Florian; Böhm, Michael C

2014-11-28

The range of validity of the Rosenfeld and Dzugutov excess entropy scaling laws is analyzed for unentangled linear polyethylene chains. We consider two segmental dynamical quantities, i.e. the bond and the torsional relaxation times, and two global ones, i.e. the chain diffusion coefficient and the viscosity. The excess entropy is approximated by either a series expansion of the entropy in terms of the pair correlation function or by an equation of state for polymers developed in the context of the self associating fluid theory. For the whole range of temperatures and chain lengths considered, the two estimates of the excess entropy are linearly correlated. The scaled bond and torsional relaxation times fall into a master curve irrespective of the chain length and the employed scaling scheme. Both quantities depend non-linearly on the excess entropy. For a fixed chain length, the reduced diffusion coefficient and viscosity scale linearly with the excess entropy. An empirical reduction to a chain length-independent master curve is accessible for both dynamic quantities. The Dzugutov scheme predicts an increased value of the scaled diffusion coefficient with increasing chain length which contrasts physical expectations. The origin of this trend can be traced back to the density dependence of the scaling factors. This finding has not been observed previously for Lennard-Jones chain systems (Macromolecules, 2013, 46, 8710-8723). Thus, it limits the applicability of the Dzugutov approach to polymers. In connection with diffusion coefficients and viscosities, the Rosenfeld scaling law appears to be of higher quality than the Dzugutov approach. An empirical excess entropy scaling is also proposed which leads to a chain length-independent correlation. It is expected to be valid for polymers in the Rouse regime.

FACTORS AFFECTING THE CHAIN LENGTH OF GROUP A STREPTOCOCCI

PubMed Central

Ekstedt, Richard D.; Stollerman, Gene H.

1960-01-01

Group A streptococci which grew in long chains in the presence of homologous anti-M antibody were split into their original length by the addition of an excess of homologous M protein to the culture. The chain-splitting reaction showed temperature and pH optima (37°C., 7.5) and was completely inhibited at 0°C. or by heat-killing the long chains at 56°C. prior to the addition of M protein. Addition of sublethal doses of HgCl2, or of penicillin, inhibited the chain-splitting reaction. Pneumococci behaved in entirely comparable fashion to streptococci in similar experiments. Virulent strains of streptococci formed the shortest chains when broth media was enriched with serum. The chain-shortening effect of serum enrichment of the media was most apparent with encapsulated strains and under cultural conditions that favored capsule formation. Loss of capsules by mutation or by unfavorable growth conditions resulted in increase in chain length. The activity of the chain-splitting mechanism seemed to be independent of M protein, however, since encapsulated M-negative variants also formed very short chain in serum-enriched media. The physical presence of the capsule was not essential for chain shortening since enzymatic removal of the capsule with hyaluronidase during growth did not affect chain length. These results strongly suggest that chain-splitting of streptococci and pneumococci occurs by an active metabolic mechanism, presumably enzymatic, which is inhibited by the union of surface antigens with specific antibody. PMID:13726267

Synthesis and Solution Properties of Adamantane Containing Quaternary Ammonium Salt-type Cationic Surfactants: Hydrocarbon-based, Fluorocarbonbased and Bola-type.

PubMed

Yoshimura, Tomokazu; Okada, Mari; Matsuoka, Keisuke

2016-10-01

Quaternary ammonium salt-type cationic surfactants with an adamantyl group (hydrocarbon-type; C n AdAB, fluorocarbon-type; C m F C 3 AdAB, bola-type; Ad-s-Ad, where n, m and s represent hydrocarbon chain lengths of 8-16, fluorocarbon chain lengths of 4-8, and spacer chain length of 10-12) were synthesized via quaternization of N, N-dimethylaminoadamantane and n-alkyl bromide or 1, n-dibromoalkane. Conductivity and surface tension were measured to characterize the solution properties of the synthesized adamantyl group-containing cationic surfactants. In addition, the effects of hydrocarbon and fluorocarbon chain lengths and spacer chain length between headgroups on the measured properties were evaluated by comparison with those of conventional cationic surfactants. The critical micelle concentration (CMC) of C n AdAB and Ad-s-Ad was 2/5 of that for the corresponding conventional surfactants C n TAB and bola-type surfactants with similar number of carbons in the alkyl or alkylene chain; this was because of the increased hydrophobicity due to the adamantyl group. A linear relationship between the logarithm of CMC and the hydrocarbon chain length for C n AdAB was observed, as well as for C n TAB. The slope of the linear correlation for both surfactants was almost the same, indicating that the adamantyl group does not affect the CMC with variations in the hydrocarbon chain length. Similar to conventional surfactants C n TAB, the hydrocarbon-type C n AdAB is highly efficient in reducing the surface tension of water, despite the large occupied area per molecule resulting from the relatively bulky structure of the adamantane skeleton. On the other hand, the bola-type Ad-s-Ad resulted in increased surface tension compared to C n AdAB, indicating that the curved chain between adamantyl groups leads to poor adsorption and orientation at the air-water interface.

In Vitro Cellular Gene Delivery Employing a Novel Composite Material of Single-Walled Carbon Nanotubes Associated With Designed Peptides With Pegylation.

PubMed

Ohta, Takahisa; Hashida, Yasuhiko; Higuchi, Yuriko; Yamashita, Fumiyoshi; Hashida, Mitsuru

2017-03-01

Single-walled carbon nanotubes (SWCNTs) attract great interest in biomedical fields including application for drug delivery system. In this study, we developed a novel gene delivery system employing SWCNTs associated with polycationic and amphiphilic H-(-Lys-Trp-Lys-Gly-) 7 -OH [(KWKG) 7 ] peptides having pegylation. SWCNTs wrapped with (KWKG) 7 formed a complex with plasmid DNA (pDNA) in aqueous solution based on polyionic interaction but later underwent aggregation. On the other hand, a complex of pDNA and SWCNT-(KWKG) 7 modified with polyethylene glycol (PEG) chains of 12 units [SWCNT-(KWKG) 7 -(PEG) 12 ] afforded good dispersion stability for 24 h even in a cell culture medium. The in vitro cellular uptake of SWCNT-(KWKG) 7 -(PEG) 12 /pDNA complex prepared with fluorescence-labeled pDNA was evaluated with fluorescent microscopic observation and flow cytometry. The uptake by A549 human lung adenocarcinoma epithelial cells increased along with the extent of pegylation, suggesting the importance of dispersion stability in addition to the cationic charge which facilitates ionic cellular interaction. The expression of pDNA encoding the monomeric Kusabira-Orange 2 fluorescent protein in the form of the SWCNT-(KWKG) 7 -(PEG) 12 /pDNA complex demonstrated remarkable enhancement of transfection depending also on the extent of pegylation and the N/P ratio. The potential of the SWCNT composite wrapped with polycationic and amphiphilic (KWKG) 7 with pegylation as a carrier for gene delivery was demonstrated. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Combinatorial Polymer Matrices Enhance In Vitro Maturation of Human Induced Pluripotent Cell Cell-Derived Cardiomyocytes

PubMed Central

Chun, Young Wook; Balikov, Daniel A.; Feaster, Tromondae K.; Williams, Charles H.; Sheng, Calvin C.; Lee, Jung-Bok; Boire, Timothy C.; Neely, M. Diana; Bellan, Leon M.; Ess, Kevin C.; Bowman, Aaron B.; Sung, Hak-Joon; Hong, Charles C.

2015-01-01

Cardiomyocytes derived from human induced pluripotent stem cells (iPSC-CMs) hold great promise for modeling human heart diseases. However, iPSC-CMs studied to date resemble immature embryonic myocytes and therefore do not adequately recapitulate native adult cardiomyocyte phenotypes. Since extracellular matrix plays an essential role in heart development and maturation in vivo, we sought to develop a synthetic culture matrix that could enhance functional maturation of iPSC-CMs in vitro. In this study, we employed a library of combinatorial polymers comprising of three functional subunits - poly-ε-caprolacton (PCL), polyethylene glycol (PEG), and carboxylated PCL (cPCL) - as synthetic substrates for culturing human iPSC-CMs. Of these, iPSC-CMs cultured on 4%PEG-96%PCL (each % indicates the corresponding molar ratio) exhibit the greatest contractility and mitochondrial function. These functional enhancements are associated with increased expression of cardiac myosin light chain-2v, cardiac troponin I and integrin alpha-7. Importantly, iPSC-CMs cultured on 4%PEG-95%PCL demonstrate troponin I (TnI) isoform switch from the fetal slow skeletal TnI (ssTnI) to the postnatal cardiac TnI (cTnI), the first report of such transition in vitro. Finally, culturing iPSC-CMs on 4%PEG-96%PCL also significantly increased expression of genes encoding intermediate filaments known to transduce integrin-mediated mechanical signals to the myofilaments. In summary, our study demonstrates that synthetic culture matrices engineered from combinatorial polymers can be utilized to promote in vitro maturation of human iPSC-CMs through the engagement of critical matrix-integrin interactions. PMID:26204225

Alcohol's Effects on Lipid Bilayer Properties

PubMed Central

Ingólfsson, Helgi I.; Andersen, Olaf S.

2011-01-01

Alcohols are known modulators of lipid bilayer properties. Their biological effects have long been attributed to their bilayer-modifying effects, but alcohols can also alter protein function through direct protein interactions. This raises the question: Do alcohol's biological actions result predominantly from direct protein-alcohol interactions or from general changes in the membrane properties? The efficacy of alcohols of various chain lengths tends to exhibit a so-called cutoff effect (i.e., increasing potency with increased chain length, which that eventually levels off). The cutoff varies depending on the assay, and numerous mechanisms have been proposed such as: limited size of the alcohol-protein interaction site, limited alcohol solubility, and a chain-length-dependent lipid bilayer-alcohol interaction. To address these issues, we determined the bilayer-modifying potency of 27 aliphatic alcohols using a gramicidin-based fluorescence assay. All of the alcohols tested (with chain lengths of 1–16 carbons) alter the bilayer properties, as sensed by a bilayer-spanning channel. The bilayer-modifying potency of the short-chain alcohols scales linearly with their bilayer partitioning; the potency tapers off at higher chain lengths, and eventually changes sign for the longest-chain alcohols, demonstrating an alcohol cutoff effect in a system that has no alcohol-binding pocket. PMID:21843475

Study on the photo-induced oxygen reordering in YBa2Cu3O6+x

NASA Astrophysics Data System (ADS)

Milić, M. M.; Lazarov, N. Dj.; Cucić, D. A.

2012-05-01

Effect of the long term illumination of the YBa2Cu3O6+x with visible light or ultraviolet irradiation on its superconducting properties was studied in the frame of a simple theoretical model, which assumes that photodoping triggers rearrangement of oxygen monomers in the chain layers thus causing the enhancement of the average chain length, lav. Since, according to the model of charge transfer mechanism, long CuO chains are better electronic hole donors than the short ones, increase of the average chain length induces additional holes transfer from chain layers to the superconducting CuO2 planes which in turn leads to the increase of the superconducting transition temperature Tc. By the use of the expression for the chain length probability distribution and numerically calculated values for the average chain length in the non-excited system, we were able to estimate the doping p (number of holes per one Cu atom in the superconducting CuO2 planes) and Tc enhancement due to photo-induced oxygen reordering. The theoretical results are compared with available experimental data.

Construct validity of the LapVR virtual-reality surgical simulator.

PubMed

Iwata, Naoki; Fujiwara, Michitaka; Kodera, Yasuhiro; Tanaka, Chie; Ohashi, Norifumi; Nakayama, Goro; Koike, Masahiko; Nakao, Akimasa

2011-02-01

Laparoscopic surgery requires fundamental skills peculiar to endoscopic procedures such as eye-hand coordination. Acquisition of such skills prior to performing actual surgery is highly desirable for favorable outcome. Virtual-reality simulators have been developed for both surgical training and assessment of performance. The aim of the current study is to show construct validity of a novel simulator, LapVR (Immersion Medical, San Jose, CA, USA), for Japanese surgeons and surgical residents. Forty-four subjects were divided into the following three groups according to their experience in laparoscopic surgery: 14 residents (RE) with no experience in laparoscopic surgery, 14 junior surgeons (JR) with little experience, and 16 experienced surgeons (EX). All subjects executed "essential task 1" programmed in the LapVR, which consists of six tasks, resulting in automatic measurement of 100 parameters indicating various aspects of laparoscopic skills. Time required for each task tended to be inversely correlated with experience in laparoscopic surgery. For the peg transfer skill, statistically significant differences were observed between EX and RE in three parameters, including total time and average time taken to complete the procedure and path length for the nondominant hand. For the cutting skill, similar differences were observed between EX and RE in total time, number of unsuccessful cutting attempts, and path length for the nondominant hand. According to the programmed comprehensive evaluation, performance in terms of successful completion of the task and actual experience of the participants in laparoscopic surgery correlated significantly for the peg transfer (P=0.007) and cutting skills (P=0.026). The peg transfer and cutting skills could best distinguish between EX and RE. This study is the first to provide evidence that LapVR has construct validity to discriminate between novice and experienced laparoscopic surgeons.

Smaller predator-prey body size ratios in longer food chains.

PubMed Central

Jennings, Simon; Warr, Karema J

2003-01-01

Maximum food-chain length has been correlated with resource availability, ecosystem size, environmental stability and colonization history. Some of these correlations may result from environmental effects on predator-prey body size ratios. We investigate relationships between maximum food-chain length, predator-prey mass ratios, primary production and environmental stability in marine food webs with a natural history of community assembly. Our analyses provide empirical evidence that smaller mean predator-prey body size ratios are characteristic of more stable environments and that food chains are longer when mean predator-prey body size ratios are small. We conclude that environmental effects on predator-prey body size ratios contribute to observed differences in maximum food-chain length. PMID:12965034

Novel odd/even effect of alkylene chain length on the photopolymerizability of organogelators.

PubMed

Aoki, Ken'ichi; Kudo, Masabumi; Tamaoki, Nobuyuki

2004-10-28

[reaction: see text] Starting from diactylene diacarboxylic acids, we have synthesized a series of photopolymerizable organogelators that possess simple amide structures, different alkylene chain lengths, and either optically active or racemic 3,7-dimethyl-1-octylamine units. The alkylene chain length of these compounds exhibits a prominent odd/even effect with respect to the photopolymerization in the gel state and is accompanied by a stereostructural effect on the gelation ability.

Thermoreversible gelation of poly(vinylidene fluoride) in phthalates: the influence of aliphatic chain length of solvents.

PubMed

Yadav, P Jaya Prakash; Ghosh, Goutam; Maiti, Biswajit; Aswal, Vinod K; Goyal, P S; Maiti, Pralay

2008-04-17

Thermoreversible gelation of poly(vinylidene fluoride) (PVDF) has been studied in a new series of solvents (phthalates), for example, dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), and dihexyl phthalate (DHP) as a function of temperature and polymer concentration, both by test tube tilting and dynamic light scattering (DLS) method. The effect of aliphatic chain length (n) of diesters on the gelation kinetics, structure/microstructure and morphology of PVDF gels has been examined. Gelation rate was found to increase with increasing aliphatic chain length of diester. DLS results indicate that the sol-gel transformation proceeds via two-steps: first, microgel domains were formed, and then the infinite three-dimensional (3D) network is established by connecting microgels through polymer chains. The crystallites are responsible for 3D network for gelation in phthalates, and alpha-polymorph is formed during gelation producing higher amount of crystallinity with increasing aliphatic chain length of diester. Morphology of the networks of dried gels in different phthalates showed that fibril thickness and lateral dimensions decrease with higher homologues of phthalates. The scattering intensity is fitted with Debye-Bueche model in small-angle neutron scattering and suggested that both the correlation length and interlamellar spacing increases with n. A model has been proposed, based on electronic structure calculations, to explain the conformation of PVDF chain in presence of various phthalates and their complexes, which offer the cause of higher gelation rate for longer aliphatic chain length.

Polyethylene glycol modified, cross-linked starch-coated iron oxide nanoparticles for enhanced magnetic tumor targeting.

PubMed

Cole, Adam J; David, Allan E; Wang, Jianxin; Galbán, Craig J; Hill, Hannah L; Yang, Victor C

2011-03-01

While successful magnetic tumor targeting of iron oxide nanoparticles has been achieved in a number of models, the rapid blood clearance of magnetically suitable particles by the reticuloendothelial system (RES) limits their availability for targeting. This work aimed to develop a long-circulating magnetic iron oxide nanoparticle (MNP) platform capable of sustained tumor exposure via the circulation and, thus, potentially enhanced magnetic tumor targeting. Aminated, cross-linked starch (DN) and aminosilane (A) coated MNPs were successfully modified with 5 kDa (A5, D5) or 20 kDa (A20, D20) polyethylene glycol (PEG) chains using simple N-Hydroxysuccinimide (NHS) chemistry and characterized. Identical PEG-weight analogues between platforms (A5 & D5, A20 & D20) were similar in size (140-190 nm) and relative PEG labeling (1.5% of surface amines - A5/D5, 0.4% - A20/D20), with all PEG-MNPs possessing magnetization properties suitable for magnetic targeting. Candidate PEG-MNPs were studied in RES simulations in vitro to predict long-circulating character. D5 and D20 performed best showing sustained size stability in cell culture medium at 37 °C and 7 (D20) to 10 (D5) fold less uptake in RAW264.7 macrophages when compared to previously targeted, unmodified starch MNPs (D). Observations in vitro were validated in vivo, with D5 (7.29 h) and D20 (11.75 h) showing much longer half-lives than D (0.12 h). Improved plasma stability enhanced tumor MNP exposure 100 (D5) to 150 (D20) fold as measured by plasma AUC(0-∞). Sustained tumor exposure over 24 h was visually confirmed in a 9L-glioma rat model (12 mg Fe/kg) using magnetic resonance imaging (MRI). Findings indicate that a polyethylene glycol modified, cross-linked starch-coated MNP is a promising platform for enhanced magnetic tumor targeting, warranting further study in tumor models. Copyright © 2010 Elsevier Ltd. All rights reserved.

Experimental and Computational Investigation of the Effect of Hydrophobicity on Aggregation and Osteoinductive Potential of BMP-2-Derived Peptide in a Hydrogel Matrix

PubMed Central

Moeinzadeh, Seyedsina; Barati, Danial; Sarvestani, Samaneh K.; Karimi, Tahereh

2015-01-01

An attractive approach to reduce the undesired side effects of bone morphogenetic proteins (BMPs) in regenerative medicine is to use osteoinductive peptide sequences derived from BMPs. Although the structure and function of BMPs have been studied extensively, there is limited data on structure and activity of BMP-derived peptides immobilized in hydrogels. The objective of this work was to investigate the effect of concentration and hydrophobicity of the BMP-2 peptide, corresponding to residues 73–92 of the knuckle epitope of BMP-2 protein, on peptide aggregation and osteogenic differentiation of human mesenchymal stem cells encapsulated in a polyethylene glycol (PEG) hydrogel. The peptide hydrophobicity was varied by capping PEG chain ends with short lactide segments. The BMP-2 peptide with a positive index of hydrophobicity had a critical micelle concentration (CMC) and formed aggregates in aqueous solution. Based on simulation results, there was a slight increase in the concentration of free peptide in solution with 1000-fold increase in peptide concentration. The dose-osteogenic response curve of the BMP-2 peptide was in the 0.0005–0.005 mM range, and osteoinductive potential of the BMP-2 peptide was significantly less than that of BMP-2 protein even at 1000-fold higher concentrations, which was attributed to peptide aggregation. Further, the peptide or PEG-peptide aggregates had significantly higher interaction energy with the cell membrane compared with the free peptide, which led to a higher nonspecific interaction with the cell membrane and loss of osteoinductive potential. Conjugation of the BMP-2 peptide to PEG increased CMC and osteoinductive potential of the peptide whereas conjugation to lactide-capped PEG reduced CMC and osteoinductive potential of the peptide. Experimental and simulation results revealed that osteoinductive potential of the BMP-2 peptide is correlated with its CMC and the free peptide concentration in aqueous medium and not the total concentration. PMID:25051457

Polyethylene Glycol Modified, Cross-Linked Starch Coated Iron Oxide Nanoparticles for Enhanced Magnetic Tumor Targeting

PubMed Central

Cole, Adam J.; David, Allan E.; Wang, Jianxin; Galbán, Craig J.; Hill, Hannah L.; Yang, Victor C.

2010-01-01

While successful magnetic tumor targeting of iron oxide nanoparticles has been achieved in a number of models, the rapid blood clearance of magnetically suitable particles by the reticuloendothelial system (RES) limits their availability for targeting. This work aimed to develop a long-circulating magnetic iron oxide nanoparticle (MNP) platform capable of sustained tumor exposure via the circulation and, thus, enhanced magnetic tumor targeting. Aminated, cross-linked starch (DN) and aminosilane (A) coated MNPs were successfully modified with 5 kDa (A5, D5) or 20 kDa (A20, D20) polyethylene glycol (PEG) chains using simple N-Hydroxysuccinimide (NHS) chemistry and characterized. Identical PEG-weight analogues between platforms (A5 & D5, A20 & D20) were similar in size (140–190 nm) and relative PEG labeling (1.5% of surface amines – A5/D5, 0.4% – A20/D20), with all PEG-MNPs possessing magnetization properties suitable for magnetic targeting. Candidate PEG-MNPs were studied in RES simulations in vitro to predict long-circulating character. D5 and D20 performed best showing sustained size stability in cell culture medium at 37°C and 7 (D20) to 10 (D5) fold less uptake in RAW264.7 macrophages when compared to previously targeted, unmodified starch MNPs (D). Observations in vitro were validated in vivo, with D5 (7.29 hr) and D20 (11.75 hr) showing much longer half-lives than D (0.12 hr). Improved plasma stability enhanced tumor MNP exposure 100 (D5) to 150 (D20) fold as measured by plasma AUC0-∞ Sustained tumor exposure over 24 hours was visually confirmed in a 9L-glioma rat model (12 mg Fe/kg) using magnetic resonance imaging (MRI). Findings indicate that both D5 and D20 are promising MNP platforms for enhanced magnetic tumor targeting, warranting further study in tumor models. PMID:21176955

Efficient CO2 capture by functionalized graphene oxide nanosheets as fillers to fabricate multi-permselective mixed matrix membranes.

PubMed

Li, Xueqin; Cheng, Youdong; Zhang, Haiyang; Wang, Shaofei; Jiang, Zhongyi; Guo, Ruili; Wu, Hong

2015-03-11

A novel multi-permselective mixed matrix membrane (MP-MMM) is developed by incorporating versatile fillers functionalized with ethylene oxide (EO) groups and an amine carrier into a polymer matrix. The as-prepared MP-MMMs can separate CO2 efficiently because of the simultaneous enhancement of diffusivity selectivity, solubility selectivity, and reactivity selectivity. To be specific, MP-MMMs were fabricated by incorporating polyethylene glycol- and polyethylenimine-functionalized graphene oxide nanosheets (PEG-PEI-GO) into a commercial low-cost Pebax matrix. The PEG-PEI-GO plays multiple roles in enhancing membrane performance. First, the high-aspect ratio GO nanosheets in a polymer matrix increase the length of the tortuous path of gas diffusion and generate a rigidified interface between the polymer matrix and fillers, enhancing the diffusivity selectivity. Second, PEG consisting of EO groups has excellent affinity for CO2 to enhance the solubility selectivity. Third, PEI with abundant primary, secondary, and tertiary amine groups reacts reversibly with CO2 to enhance reactivity selectivity. Thus, the as-prepared MP-MMMs exhibit excellent CO2 permeability and CO2/gas selectivity. The MP-MMM doped with 10 wt % PEG-PEI-GO displays optimal gas separation performance with a CO2 permeability of 1330 Barrer, a CO2/CH4 selectivity of 45, and a CO2/N2 selectivity of 120, surpassing the upper bound lines of the Robeson study of 2008 (1 Barrer = 10(-10) cm(3) (STP) cm(-2) s(-1) cm(-1) Hg).

Cellular uptake and intracellular trafficking of PEG-b-PLA polymeric micelles.

PubMed

Zhang, Zhen; Xiong, Xiaoqin; Wan, Jiangling; Xiao, Ling; Gan, Lu; Feng, Youmei; Xu, Huibi; Yang, Xiangliang

2012-10-01

Besides as an inert carrier for hydrophobic anticancer agents, polymeric micelles composed of di-block copolymer poly(ethylene glycol)-poly(lactic acid) (PEG-b-PLA) function as biological response modifiers including reversal of multidrug resistance in cancer. However, the uptake mechanisms and the subsequent intracellular trafficking remain to be elucidated. In this paper, we found that the uptake of PEG-b-PLA polymeric micelles incorporating nile red (M-NR) was significantly inhibited by both dynamin inhibitor dynasore and dynamin-2 dominant negative mutant (dynamin-2 K44A). Exogenously expressed caveolin-1 colocalized with M-NR and upregulated M-NR internalization in HepG2 cells expressing low level of endogenous caveolin-1, while caveolin-1 dominant negative mutant (caveolin-1 Y14F) significantly downregulated M-NR internalization in C6 cells expressing high level of endogenous caveolin-1. Exogenously expressed clathrin light chain A (clathrin LCa) did not mainly colocalize with the internalized M-NR and had no effect on M-NR uptake. These results suggested that dynamin- and caveolin-dependent but clathrin-independent endocytosis was involved in M-NR cellular uptake. We further found that M-NR colocalized with lysosome and microtubulin after internalization. Copyright © 2012 Elsevier Ltd. All rights reserved.

Absorption, distribution, metabolism and excretion of peginesatide, a novel erythropoiesis-stimulating agent, in rats

PubMed Central

Woodburn, Kathryn W.; Holmes, Christopher P.; Wilson, Susan D.; Fong, Kei-Lai; Press, Randall J.; Moriya, Yuu; Tagawa, Yoshihiko

2011-01-01

The pharmacokinetics(PK) (absorption, distribution, metabolism, excretion) of peginesatide.a synthetic, PEGylated, investigational, peptide-based erythropoiesis-stimulating agent (ESA), was evaluated in rats. The PK profile was evaluated at 0.1-5 mg·kg−1 IV using unlabeled or [14C]-labeled peginesatide. Mass balance, tissue distribution and metabolism were evaluated following IV administration of 5 mg·kg−1 [14C]-peginesatide, with tissue distribution also evaluated by quantitative whole-body autoradiography (QWBA) following an IV dose of 17 mg·kg−1[14C]-peginesatide. Plasma clearance was slow and elimination was biphasic with unchanged peginesatide representing >90% of the total radioactivity of the total radioactive exposure. Slow uptake of the radiolabeled compound from the vascular compartment into the tissues was observed. Biodistribution to bone marrow and extramedullary hematopoietic sites, and to highly vascularized lymphatic and excretory tissues occurred. A predominant degradation event to occur in vivo was the loss of one PEG chain from the branched PEG moiety to generate mono-PEG. Renal excretion was the primary mechanism (41%) of elimination, with parent molecule (67%) the major moiety excreted. In conclusion, elimination of [14C]-peginesatide-derived radioactivity was extended, retention preferentially occurred at sites of erythropoiesis (bone marrow), and urinary excretion was the primary elimination route. PMID:22188389

Evaluation of an in situ chemically crosslinked hydrogel as a long-term vitreous substitute material.

PubMed

Tao, Yong; Tong, Xinming; Zhang, Yan; Lai, Jingjing; Huang, Yanbin; Jiang, Yan-Rong; Guo, Bao-Hua

2013-02-01

Currently there is no material that can be used as a long-term vitreous substitute, and this remains an unmet clinical need in ophthalmology. In this study, we developed an injectable, in situ chemically crosslinked hydrogel system and evaluated it in a rabbit model. The system consisted of two components, both based on multi-functional poly(ethylene glycol) (PEG) but with complementarily reactive end groups of thiol and active vinyl groups, respectively. The two components are mixed and injected as a solution mixture, react in vivo via the Michael addition route and form a chemically crosslinked hydrogel in situ. The linkages between the end groups and the backbone PEG chains are specially designed to ensure that the final network structure is hydrolysis-resistant. In the rabbit study and with an optimized operation protocol, we demonstrated that the hydrogel indeed formed in situ after injection, and remained transparent and stable during the study period of 9 months without significant adverse reactions. In addition, the hydrogel formed in situ showed rheological properties very similar to the natural vitreous. Therefore, our study demonstrated that this in situ chemically crosslinked PEG gel system is suitable as a potential long-term vitreous substitute. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Block copolymer micelles for controlled delivery of glycolytic enzyme inhibitors.

PubMed

Akter, Shanjida; Clem, Brian F; Lee, Hyun Jin; Chesney, Jason; Bae, Younsoo

2012-03-01

To develop block copolymer micelles as an aqueous dosage form for a potent glycolytic enzyme inhibitor, 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO). The micelles were prepared from poly(ethylene glycol)-poly(aspartate hydrazide) [PEG-p(HYD)] block copolymers to which 3PO was conjugated through an acid-labile hydrazone bond. The optimal micelle formulation was determined following the screening of block copolymer library modified with various aromatic and aliphatic pendant groups. Both physical drug entrapment and chemical drug conjugation methods were tested to maximize 3PO loading in the micelles during the screening. Particulate characterization showed that the PEG-p(HYD) block copolymers conjugated with 3PO (2.08∼2.21 wt.%) appeared the optimal polymer micelles. Block copolymer compositions greatly affected the micelle size, which was 38 nm and 259 nm when 5 kDa and 12 kDa PEG chains were used, respectively. 3PO release from the micelles was accelerated at pH 5.0, potentiating effective drug release in acidic tumor environments. The micelles retained biological activity of 3PO, inhibiting various cancer cells (Jurkat, He-La and LLC) in concentration ranges similar to free 3PO. A novel micelle formulation for controlled delivery of 3PO was successfully prepared.

Mass spectrometric behaviour of carboxylated polyethylene glycols and carboxylated octylphenol ethoxylates.

PubMed

Frańska, Magdalena; Zgoła, Agnieszka; Rychłowska, Joanna; Szymański, Andrzej; Łukaszewski, Zenon; Frański, Rafał

2003-01-01

Mass spectrometric behaviour of mono- and di-carboxylated polyethylene glycols (PEGCs and CPEGCs) and carboxylated octylphenol ethoxylates (OPECs) are discussed. The tendency for ionisation (deprotonation, protonation and cationisation by alkali metal cations) of carboxylated PEGs was compared with that of non-carboxylated correspondents by using both secondary ion mass spectrometry (SIMS) and electrospray ionisation (ESI). The fragmentation of the PEGCs and CPEGCs is discussed and also compared with their neutral correspondents, PEGs. The B/E mass spectra were recorded, using secondary ion mass spectrometry as a method for generation, for deprotonated and protonated molecules and molecules cationised by alkali metal cations. The fragmentation behaviour of PEGs is found to be different from that of CPEGCs, The presence of carboxylic groups may be confirmed not only by the determination of molecular weights of the ethoxylates studied, but also on the basis of the fragment ions formed. The metastable decomposition of the [OPEC-H](-) ions proceed through the cleavage of the bond between the octylphenol moiety and the ethoxylene chain leading to the octylphenoxy anions. It permits determination of the mass of the hydrophobic moiety of the studied carboxylated alkylphenol ethoxylate. ESI mass spectra recorded in the negative ion mode were found to be more suitable for the determination of the average molecular weight of carboxylated ethoxylates than SI mass spectra.

Antennal sensilla of the stonefly Dinocras cephalotes (Plecoptera: Perlidae).

PubMed

Rebora, Manuela; Tierno de Figueroa, José Manuel; Piersanti, Silvana

2016-11-01

Plecoptera, one of the most primitive groups of Neoptera, are important aquatic insects usually employed as bioindicators of high water quality. Notwithstanding the well-developed antennae of the adult, its sensory abilities are so far not well known. The present paper describes at ultrastructural level under scanning and transmission electron microscopy the antennal sensilla of the adult stonefly Dinocras cephalotes (Plecoptera, Perlidae). Adult males and females show a filiform antenna constituted of a scape, a pedicel and a flagellum composed of very numerous segments with no clear sexual dimorphism in the number and distribution of the antennal sensilla. The most represented sensilla are sensilla trichodea, with different length, whose internal structure reveal their mechanosensory function, sensilla chaetica, with an apical pore, with an internal structure revealing a typical gustatory function, porous pegs representing single-walled olfactory sensilla, digitated pegs with hollow cuticular spoke channels representing double-walled olfactory sensilla, pegs in pits for which we hypothesize a thermo-hygrosensory function. The diversity of described sensilla is discussed in relation to known biological aspects of the studied species. This opens new perspectives in the study of the behavior of these aquatic insects during their adult stage. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Ultrasensitivity of Living Polymers

NASA Astrophysics Data System (ADS)

O'Shaughnessy, Ben; Vavylonis, Dimitrios

2003-03-01

Synthetic and biological living polymers are self-assembling chains whose chain length distributions (CLDs) are dynamic. We show these dynamics are ultrasensitive: Even a small perturbation (e.g., temperature jump) nonlinearly distorts the CLD, eliminating or massively augmenting short chains. The origin is fast relaxation of mass variables (mean chain length, monomer concentration) which perturbs CLD shape variables before these can relax via slow chain growth rate fluctuations. Viscosity relaxation predictions agree with experiments on the best-studied synthetic system, α-methylstyrene.

Analysis of Nuclear Factor-κB (NF-κB) Essential Modulator (NEMO) Binding to Linear and Lysine-linked Ubiquitin Chains and Its Role in the Activation of NF-κB*

PubMed Central

Kensche, Tobias; Tokunaga, Fuminori; Ikeda, Fumiyo; Goto, Eiji; Iwai, Kazuhiro; Dikic, Ivan

2012-01-01

Nuclear factor-κB (NF-κB) essential modulator (NEMO), a component of the inhibitor of κB kinase (IKK) complex, controls NF-κB signaling by binding to ubiquitin chains. Structural studies of NEMO provided a rationale for the specific binding between the UBAN (ubiquitin binding in ABIN and NEMO) domain of NEMO and linear (Met-1-linked) di-ubiquitin chains. Full-length NEMO can also interact with Lys-11-, Lys-48-, and Lys-63-linked ubiquitin chains of varying length in cells. Here, we show that purified full-length NEMO binds preferentially to linear ubiquitin chains in competition with lysine-linked ubiquitin chains of defined length, including long Lys-63-linked deca-ubiquitins. Linear di-ubiquitins were sufficient to activate both the IKK complex in vitro and to trigger maximal NF-κB activation in cells. In TNFα-stimulated cells, NEMO chimeras engineered to bind exclusively to Lys-63-linked ubiquitin chains mediated partial NF-κB activation compared with cells expressing NEMO that binds to linear ubiquitin chains. We propose that NEMO functions as a high affinity receptor for linear ubiquitin chains and a low affinity receptor for long lysine-linked ubiquitin chains. This phenomenon could explain quantitatively distinct NF-κB activation patterns in response to numerous cell stimuli. PMID:22605335

Application of Nitrogen and Carbon Stable Isotopes (δ15N and δ13C) to Quantify Food Chain Length and Trophic Structure

PubMed Central

Perkins, Matthew J.; McDonald, Robbie A.; van Veen, F. J. Frank; Kelly, Simon D.; Rees, Gareth; Bearhop, Stuart

2014-01-01

Increasingly, stable isotope ratios of nitrogen (δ15N) and carbon (δ13C) are used to quantify trophic structure, though relatively few studies have tested accuracy of isotopic structural measures. For laboratory-raised and wild-collected plant-invertebrate food chains spanning four trophic levels we estimated nitrogen range (NR) using δ15N, and carbon range (CR) using δ13C, which are used to quantify food chain length and breadth of trophic resources respectively. Across a range of known food chain lengths we examined how NR and CR changed within and between food chains. Our isotopic estimates of structure are robust because they were calculated using resampling procedures that propagate variance in sample means through to quantified uncertainty in final estimates. To identify origins of uncertainty in estimates of NR and CR, we additionally examined variation in discrimination (which is change in δ15N or δ13C from source to consumer) between trophic levels and among food chains. δ15N discrimination showed significant enrichment, while variation in enrichment was species and system specific, ranged broadly (1.4‰ to 3.3‰), and importantly, propagated variation to subsequent estimates of NR. However, NR proved robust to such variation and distinguished food chain length well, though some overlap between longer food chains infers a need for awareness of such limitations. δ13C discrimination was inconsistent; generally no change or small significant enrichment was observed. Consequently, estimates of CR changed little with increasing food chain length, showing the potential utility of δ13C as a tracer of energy pathways. This study serves as a robust test of isotopic quantification of food chain structure, and given global estimates of aquatic food chains approximate four trophic levels while many food chains include invertebrates, our use of four trophic level plant-invertebrate food chains makes our findings relevant for a majority of ecological systems. PMID:24676331

Effects of Polymer Conjugation on Hybridization Thermodynamics of Oligonucleic Acids.

PubMed

Ghobadi, Ahmadreza F; Jayaraman, Arthi

2016-09-15

In this work, we perform coarse-grained (CG) and atomistic simulations to study the effects of polymer conjugation on hybridization/melting thermodynamics of oligonucleic acids (ONAs). We present coarse-grained Langevin molecular dynamics simulations (CG-NVT) to assess the effects of the polymer flexibility, length, and architecture on hybridization/melting of ONAs with different ONA duplex sequences, backbone chemistry, and duplex concentration. In these CG-NVT simulations, we use our recently developed CG model of ONAs in implicit solvent, and treat the conjugated polymer as a CG chain with purely repulsive Weeks-Chandler-Andersen interactions with all other species in the system. We find that 8-100-mer linear polymer conjugation destabilizes 8-mer ONA duplexes with weaker Watson-Crick hydrogen bonding (WC H-bonding) interactions at low duplex concentrations, while the same polymer conjugation has an insignificant impact on 8-mer ONA duplexes with stronger WC H-bonding. To ensure the configurational space is sampled properly in the CG-NVT simulations, we also perform CG well-tempered metadynamics simulations (CG-NVT-MetaD) and analyze the free energy landscape of ONA hybridization for a select few systems. We demonstrate that CG-NVT-MetaD simulation results are consistent with the CG-NVT simulations for the studied systems. To examine the limitations of coarse-graining in capturing ONA-polymer interactions, we perform atomistic parallel tempering metadynamics simulations at well-tempered ensemble (AA-MetaD) for a 4-mer DNA in explicit water with and without conjugation to 8-mer poly(ethylene glycol) (PEG). AA-MetaD simulations also show that, for a short DNA duplex at T = 300 K, a condition where the DNA duplex is unstable, conjugation with PEG further destabilizes DNA duplex. We conclude with a comparison of results from these three different types of simulations and discuss their limitations and strengths.

Identification of a 467 bp Promoter of Maize Phosphatidylinositol Synthase Gene (ZmPIS) Which Confers High-Level Gene Expression and Salinity or Osmotic Stress Inducibility in Transgenic Tobacco

PubMed Central

Zhang, Hongli; Hou, Jiajia; Jiang, Pingping; Qi, Shoumei; Xu, Changzheng; He, Qiuxia; Ding, Zhaohua; Wang, Zhiwu; Zhang, Kewei; Li, Kunpeng

2016-01-01

Salinity and drought often affect plant growth and crop yields. Cloning and identification of salinity and drought stress inducible promoters is of great significance for their use in the genetic improvement of crop resistance. Previous studies showed that phosphatidylinositol synthase is involved in plant salinity and drought stress responses but its promoter has not been characterized by far. In the study, the promoter (pZmPIS, 1834 bp upstream region of the translation initiation site) was isolated from maize genome. To functionally validate the promoter, eight 5′ deletion fragments of pZmPIS in different lengths were fused to GUS to produce pZmPIS::GUS constructs and transformed into tobacco, namely PZ1–PZ8. The transcription activity and expression pattern obviously changed when the promoter was truncated. Previous studies have demonstrated that NaCl and PEG treatments are usually used to simulate salinity and drought treatments. The results showed that PZ1–PZ7 can respond well upon NaCl and PEG treatments, while PZ8 not. PZ7 (467 bp) displayed the highest transcription activity in all tissues of transgenic tobacco amongst 5′ deleted promoter fragments, which corresponds to about 20 and 50% of CaMV35S under normal and NaCl or PEG treatment, respectively. This implied that PZ7 is the core region of pZmPIS which confers high-level gene expression and NaCl or PEG inducible nature. The 113 bp segment between PZ7 and PZ8 (-467 to -355 bp) was considered as the key sequence for ZmPIS responding to NaCl or PEG treatment. GUS transient assay in tobacco leaves showed that this segment was sufficient for the NaCl or PEG stress response. Bioinformatic analysis revealed that the 113 bp sequence may contain new elements that are crucial for ZmPIS response to NaCl or PEG stress. These results promote our understanding on transcriptional regulation mechanism of ZmPIS and the characterized PZ7 promoter fragment would be an ideal candidate for the overexpression of drought and salinity responsive gene to improve crop resistance. PMID:26870063

Branching, Chain Scission, and Solution Stability of Worm-Like Micelles

NASA Astrophysics Data System (ADS)

Beaucage, Greg; Vogtt, Karsten; Jiang, Hanqui

As salt is added to a simple micelle solution such as SDS or SLES, the zero shear rate specific viscosity rises rapidly followed by a maximum and decay. The rapid rise in viscosity is associated with formation of elliptical and extended chain worm-like micelles, WLMs. Entanglement of these long chain micelles leads to the viscoelastic behavior we associate with shampoo and body wash. The plateau and drop in viscosity at high salt concentrations is caused by a special type of topological branching where the branch points have no energy penalty to motion along the chain according to Cates theory. These have some similarity to catenane crosslinks. Predictive dynamic theories for WLMs rely on structural details; the diameter, persistence length, contour length, branch length, segment length between branch points, and mesh size. Further, since the contour length and other large scale features are in kinetic equilibrium, with frequent chain breakage and formation, the thermodynamics of these long chain structures are of interest both in terms of chain scission as well as in terms of the stability of the colloidal solution as a whole. Recent structural studies of WLMs using static neutron scattering based on new scattering models will be presented demonstrating that these input parameters for dynamic models of complex topological systems are quantitatively and directly available. In this context it is important to consider a comparison between dynamic features, for instance entanglement, and their static analogs, chain overlap.

Embryonic catalase protects against ethanol embryopathies in acatalasemic mice and transgenic human catalase-expressing mice in embryo culture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller-Pinsler, Lutfiya; Wells, Peter G., E-mail: pg.wells@utoronto.ca; Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario

Reactive oxygen species (ROS) have been implicated in the mechanism of ethanol (EtOH) teratogenicity, but the protective role of the embryonic antioxidative enzyme catalase is unclear, as embryonic activity is only about 5% of maternal levels. We addressed this question in a whole embryo culture model. C57BL/6 mouse embryos expressing human catalase (hCat) or their wild-type (C57BL/6 WT) controls, and C3Ga.Cg-Cat{sup b}/J catalase-deficient, acatalasemic (aCat) mouse embryos or their wild-type C3HeB/FeJ (C3H WT) controls, were explanted on gestational day (GD) 9 (plug = GD 1), exposed for 24 h to 2 or 4 mg/mL EtOH or vehicle, and evaluated formore » functional and morphological changes. hCat and C57BL/6 WT vehicle-exposed embryos developed normally, while EtOH was embryopathic in C57BL/6 WT embryos, evidenced by decreases in anterior neuropore closure, somites developed, turning and head length, whereas hCat embryos were protected (p < 0.001). Maternal pretreatment of C57BL/6 WT dams with 50 kU/kg PEG-catalase (PEG-cat) 8 h prior to embryo culture, which increases embryonic catalase activity, blocked all EtOH embryopathies (p < 0.001). Vehicle-exposed aCat mouse embryos had lower yolk sac diameters compared to WT controls, suggesting that endogenous ROS are embryopathic. EtOH was more embryopathic in aCat embryos than WT controls, evidenced by reduced head length and somite development (p < 0.01), and trends for reduced anterior neuropore closure, turning and crown–rump length. Maternal pretreatment of aCat dams with PEG-Cat blocked all EtOH embryopathies (p < 0.05). These data suggest that embryonic catalase is a determinant of risk for EtOH embryopathies. - Highlights: • Ethanol (EtOH) exposure causes structural embryopathies in embryo culture. • Genetically enhanced catalase (hCat) protects against EtOH embryopathies. • Genetically deficient catalase (aCat) exacerbates EtOH embryopathies. • Embryonic catalase is developmentally important. • EtOH developmental toxicity involves reactive oxygen species formation.« less

Mapping bright and dark modes in gold nanoparticle chains using electron energy loss spectroscopy.

PubMed

Barrow, Steven J; Rossouw, David; Funston, Alison M; Botton, Gianluigi A; Mulvaney, Paul

2014-07-09

We present a scanning transmission electron microscopy-electron energy loss spectroscopy (STEM-EELS) investigation of gold nanosphere chains with lengths varying from 1 to 5 particles. We show localized EELS signals from the chains and identify energy-loss peaks arising due to l = 1, 2, 3, 4, and 5 plasmon modes through the use of EELS mapping. We also show the evolution of the energy of these modes as the length of a given chain increases, and we find that a chain containing N particles can accommodate at least N experimentally observable modes, in addition to the transverse mode. As the chain length is increased by the addition of one more gold particle to the chain, the new N + 1 mode becomes the highest energy mode, while the existing modes lower their energy and eventually asymptote as they delocalize along the chain. We also show that modes become increasingly difficult to detect with the EELS technique as l approaches N. The data are compared to numerical simulations.

Sequence-Independent Cloning and Post-Translational Modification of Repetitive Protein Polymers through Sortase and Sfp-Mediated Enzymatic Ligation.

PubMed

Ott, Wolfgang; Nicolaus, Thomas; Gaub, Hermann E; Nash, Michael A

2016-04-11

Repetitive protein-based polymers are important for many applications in biotechnology and biomaterials development. Here we describe the sequential additive ligation of highly repetitive DNA sequences, their assembly into genes encoding protein-polymers with precisely tunable lengths and compositions, and their end-specific post-translational modification with organic dyes and fluorescent protein domains. Our new Golden Gate-based cloning approach relies on incorporation of only type IIS BsaI restriction enzyme recognition sites using PCR, which allowed us to install ybbR-peptide tags, Sortase c-tags, and cysteine residues onto either end of the repetitive gene polymers without leaving residual cloning scars. The assembled genes were expressed in Escherichia coli and purified using inverse transition cycling (ITC). Characterization by cloud point spectrophotometry, and denaturing polyacrylamide gel electrophoresis with fluorescence detection confirmed successful phosphopantetheinyl transferase (Sfp)-mediated post-translational N-terminal labeling of the protein-polymers with a coenzyme A-647 dye (CoA-647) and simultaneous sortase-mediated C-terminal labeling with a GFP domain containing an N-terminal GG-motif in a one-pot reaction. In a further demonstration, we installed an N-terminal cysteine residue into an elastin-like polypeptide (ELP) that was subsequently conjugated to a single chain poly(ethylene glycol)-maleimide (PEG-maleimide) synthetic polymer, noticeably shifting the ELP cloud point. The ability to straightforwardly assemble repetitive DNA sequences encoding ELPs of precisely tunable length and to post-translationally modify them specifically at the N- and C- termini provides a versatile platform for the design and production of multifunctional smart protein-polymeric materials.

Quantifying Short-Chain Chlorinated Paraffin Congener Groups.

PubMed

Yuan, Bo; Bogdal, Christian; Berger, Urs; MacLeod, Matthew; Gebbink, Wouter A; Alsberg, Tomas; de Wit, Cynthia A

2017-09-19

Accurate quantification of short-chain chlorinated paraffins (SCCPs) poses an exceptional challenge to analytical chemists. SCCPs are complex mixtures of chlorinated alkanes with variable chain length and chlorination level; congeners with a fixed chain length (n) and number of chlorines (m) are referred to as a "congener group" C n Cl m . Recently, we resolved individual C n Cl m by mathematically deconvolving soft ionization high-resolution mass spectra of SCCP mixtures. Here we extend the method to quantifying C n Cl m by introducing C n Cl m specific response factors (RFs) that are calculated from 17 SCCP chain-length standards with a single carbon chain length and variable chlorination level. The signal pattern of each standard is measured on APCI-QTOF-MS. RFs of each C n Cl m are obtained by pairwise optimization of the normal distribution's fit to the signal patterns of the 17 chain-length standards. The method was verified by quantifying SCCP technical mixtures and spiked environmental samples with accuracies of 82-123% and 76-109%, respectively. The absolute differences between calculated and manufacturer-reported chlorination degrees were -0.9 to 1.0%Cl for SCCP mixtures of 49-71%Cl. The quantification method has been replicated with ECNI magnetic sector MS and ECNI-Q-Orbitrap-MS. C n Cl m concentrations determined with the three instruments were highly correlated (R 2 > 0.90) with each other.

Well-defined block copolymers for gene delivery to dendritic cells: probing the effect of polycation chain-length.

PubMed

Tang, Rupei; Palumbo, R Noelle; Nagarajan, Lakshmi; Krogstad, Emily; Wang, Chun

2010-03-03

The development of safe and efficient polymer carriers for DNA vaccine delivery requires mechanistic understanding of structure-function relationship of the polymer carriers and their interaction with antigen-presenting cells. Here we have synthesized a series of diblock copolymers with well-defined chain-length using atom transfer radical polymerization and characterized the influence of polycation chain-length on the physico-chemical properties of the polymer/DNA complexes as well as the interaction with dendritic cells. The copolymers consist of a hydrophilic poly(ethylene glycol) block and a cationic poly(aminoethyl methacrylate) (PAEM) block. The average degree of polymerization (DP) of the PAEM block was varied among 19, 39, and 75, with nearly uniform distribution. With increasing PAEM chain-length, polyplexes formed by the diblock copolymers and plasmid DNA had smaller average particle size and showed higher stability against electrostatic destabilization by salt and heparin. The polymers were not toxic to mouse dendritic cells (DCs) and only displayed chain-length-dependent toxicity at a high concentration (1mg/mL). In vitro gene transfection efficiency and polyplex uptake in DCs were also found to correlate with chain-length of the PAEM block with the longer polymer chain favoring transfection and cellular uptake. The polyplexes induced a modest up-regulation of surface markers for DC maturation that was not significantly dependent on PAEM chain-length. Finally, the polyplex prepared from the longest PAEM block (DP of 75) achieved an average of 20% enhancement over non-condensed anionic dextran in terms of uptake by DCs in the draining lymph nodes 24h after subcutaneous injection into mice. Insights gained from studying such structurally well-defined polymer carriers and their interaction with dendritic cells may contribute to improved design of practically useful DNA vaccine delivery systems. Copyright 2009 Elsevier B.V. All rights reserved.

A novel nanoemulsion-based method to produce ultrasmall, water-dispersible nanoparticles from chitosan, surface modified with cell-penetrating peptide for oral delivery of proteins and peptides

PubMed Central

Barbari, Ghullam Reza; Dorkoosh, Farid Abedin; Amini, Mohsen; Sharifzadeh, Mohammad; Atyabi, Fateme; Balalaie, Saeed; Rafiee Tehrani, Niyousha; Rafiee Tehrani, Morteza

2017-01-01

A simple and reproducible water-in-oil (W/O) nanoemulsion technique for making ultrasmall (<15 nm), monodispersed and water-dispersible nanoparticles (NPs) from chitosan (CS) is reported. The nano-sized (50 nm) water pools of the W/O nanoemulsion serve as “nano-containers and nano-reactors”. The entrapped polymer chains of CS inside these “nano-reactors” are covalently cross-linked with the chains of polyethylene glycol (PEG), leading to rigidification and formation of NPs. These NPs possess excessive swelling properties in aqueous medium and preserve integrity in all pH ranges due to chemical cross-linking with PEG. A potent and newly developed cell-penetrating peptide (CPP) is further chemically conjugated to the surface of the NPs, leading to development of a novel peptide-conjugated derivative of CS with profound tight-junction opening properties. The CPP-conjugated NPs can easily be loaded with almost all kinds of proteins, peptides and nucleotides for oral delivery applications. Feasibility of this nanoparticulate system for oral delivery of a model peptide (insulin) is investigated in Caco-2 cell line. The cell culture results for translocation of insulin across the cell monolayer are very promising (15%–19% increase), and animal studies are actively under progress and will be published separately. PMID:28496323

Added value of lignin as lignin-based hybrid polyurethane for a compatibilizing agent

NASA Astrophysics Data System (ADS)

Ilmiati, S.; Haris Mustafa, J.; Yaumal, A.; Hanum, F.; Chalid, M.

2017-07-01

As biomass-based material, lignin contains abundant hydroxyl groups promising to be used as chain extender in building hybrid polyurethanes. Consisting of polyehtylene glycol (PEG) content as hydrophobic part and lignin as hydrophilic part, the hybrid PU is expected to be as a novel compatibilizing agent in new materials production such as polyblends and composites. The hybrid PU was synthesized via two reaction stages, viz. pre-polyurethanization through reacting 4,4'-Methylenebis (Cyclohexyl Isocyanate) (HMDI) and PEG as polyol, and chain extention through adding lignin in the pre-polyurethanization system. The composition effect of lignin in hybrid PU syntehsis, to chemical structure corelated to hydrophobic to hydrophilic ratio, thermal and morphological properties, was evaluated by measuring NMR, FTIR, DSC, TGA and FE-SEM. The experiments showed that addition of lignin was able to extend the pre-polyurethane into hybrid polyurethane and to increase the lignin/polyol ratio in the hybrid polyurethanes, which were indicated by NMR and FTIR Analysis. And change of the ratio lead to increase the glass transition from 60.9 until 62.1°C and degradation temperature from 413.9 until 416.0°C. Observation of the morphology implied that addition of lignin gave more agglomerations. A Further investigation for this characterization study should be focused on a feasibility for this modified lignin as a novel compatibilizing agent.

A Motor-Driven Mechanism for Cell-Length Sensing

PubMed Central

Rishal, Ida; Kam, Naaman; Perry, Rotem Ben-Tov; Shinder, Vera; Fisher, Elizabeth M.C.; Schiavo, Giampietro; Fainzilber, Mike

2012-01-01

Summary Size homeostasis is fundamental in cell biology, but it is not clear how large cells such as neurons can assess their own size or length. We examined a role for molecular motors in intracellular length sensing. Computational simulations suggest that spatial information can be encoded by the frequency of an oscillating retrograde signal arising from a composite negative feedback loop between bidirectional motor-dependent signals. The model predicts that decreasing either or both anterograde or retrograde signals should increase cell length, and this prediction was confirmed upon application of siRNAs for specific kinesin and/or dynein heavy chains in adult sensory neurons. Heterozygous dynein heavy chain 1 mutant sensory neurons also exhibited increased lengths both in vitro and during embryonic development. Moreover, similar length increases were observed in mouse embryonic fibroblasts upon partial downregulation of dynein heavy chain 1. Thus, molecular motors critically influence cell-length sensing and growth control. PMID:22773964

Flexible polyelectrolyte chain in a strong electrolyte solution: Insight into equilibrium properties and force-extension behavior from mesoscale simulation

NASA Astrophysics Data System (ADS)

Malekzadeh Moghani, Mahdy; Khomami, Bamin

2016-01-01

Macromolecules with ionizable groups are ubiquitous in biological and synthetic systems. Due to the complex interaction between chain and electrostatic decorrelation lengths, both equilibrium properties and micro-mechanical response of dilute solutions of polyelectrolytes (PEs) are more complex than their neutral counterparts. In this work, the bead-rod micromechanical description of a chain is used to perform hi-fidelity Brownian dynamics simulation of dilute PE solutions to ascertain the self-similar equilibrium behavior of PE chains with various linear charge densities, scaling of the Kuhn step length (lE) with salt concentration cs and the force-extension behavior of the PE chain. In accord with earlier theoretical predictions, our results indicate that for a chain with n Kuhn segments, lE ˜ cs-0.5 as linear charge density approaches 1/n. Moreover, the constant force ensemble simulation results accurately predict the initial non-linear force-extension region of PE chain recently measured via single chain experiments. Finally, inspired by Cohen's extraction of Warner's force law from the inverse Langevin force law, a novel numerical scheme is developed to extract a new elastic force law for real chains from our discrete set of force-extension data similar to Padè expansion, which accurately depicts the initial non-linear region where the total Kuhn length is less than the thermal screening length.

Flexible polyelectrolyte chain in a strong electrolyte solution: Insight into equilibrium properties and force-extension behavior from mesoscale simulation.

PubMed

Malekzadeh Moghani, Mahdy; Khomami, Bamin

2016-01-14

Macromolecules with ionizable groups are ubiquitous in biological and synthetic systems. Due to the complex interaction between chain and electrostatic decorrelation lengths, both equilibrium properties and micro-mechanical response of dilute solutions of polyelectrolytes (PEs) are more complex than their neutral counterparts. In this work, the bead-rod micromechanical description of a chain is used to perform hi-fidelity Brownian dynamics simulation of dilute PE solutions to ascertain the self-similar equilibrium behavior of PE chains with various linear charge densities, scaling of the Kuhn step length (lE) with salt concentration cs and the force-extension behavior of the PE chain. In accord with earlier theoretical predictions, our results indicate that for a chain with n Kuhn segments, lE ∼ cs (-0.5) as linear charge density approaches 1/n. Moreover, the constant force ensemble simulation results accurately predict the initial non-linear force-extension region of PE chain recently measured via single chain experiments. Finally, inspired by Cohen's extraction of Warner's force law from the inverse Langevin force law, a novel numerical scheme is developed to extract a new elastic force law for real chains from our discrete set of force-extension data similar to Padè expansion, which accurately depicts the initial non-linear region where the total Kuhn length is less than the thermal screening length.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Y Hu; D Samanta; S Parelkar

Controlled free radical polymerization chemistry is used to graft polymer chains to the corona of horse spleen ferritin (HSF) nanocages. Specifically, poly(methacryloyloxyethyl phosphorylcholine) (polyMPC) and poly(PEG methacrylate) (polyPEGMA) chains are grafted onto the nanocages by atom transfer radical polymerization (ATRP), in which the molecular weight of the polymer grafts is controlled by the monomer-to-initiator feed ratio. PolyMPC and polyPEGMA-grafted ferritin show a generally suppressed inclusion into diblock copolymer films relative to native ferritin, and the polymer coating is seen to mask the ferritin nanocages from antibody recognition. The solubility of polyPEGMA-coated ferritin in organic solvents enables its processing with polystyrene-block-poly(ethylenemore » oxide) copolymers, and selective integration into the PEO domains of microphase-separated copolymer structures.« less

Differences in the adsorption behaviour of poly(ethylene oxide) copolymers onto model polystyrene nanoparticles assessed by isothermal titration microcalorimetry correspond to the biological differences.

PubMed

Stolnik, S; Heald, C R; Garnett, M G; Illum, L; Davis, S S

2005-01-01

The adsorption behaviour of a tetrafunctional copolymer of poly (ethylene oxide)-poly (propylene oxide) ethylene diamine (commercially available as Poloxamine 908) and a diblock copolymer of poly (lactic acid)-poly (ethylene oxide) (PLA/PEG 2:5) onto a model colloidal drug carrier (156 nm sized polystyrene latex) is described. The adsorption isotherm, hydrodynamic thickness of the adsorbed layers and enthalpy of the adsorption were assessed. The close similarity in the conformation of the poly (ethylene oxide) (PEO) chains (molecular weight 5,000 Da) in the adsorbed layers of these two copolymers was demonstrated by combining the adsorption data with the adsorbed layer thickness data. In contrast, the results from isothermal titration microcalorimetry indicated a distinct difference in the interaction of the copolymers with the polystyrene colloid surface. Poloxamine 908 adsorption to polystyrene nanoparticles is dominated by an endothermic heat effect, whereas, PLA/PEG 2:5 adsorption is entirely an exothermic process. This difference in adsorption behaviour could provide an explanation for differences in the biodistribution of Poloxamine 908 and PLA/PEG 2:5 coated polystyrene nanoparticles observed in previous studies. A comparison with the interaction enthalpy for several other PEO-containing copolymers onto the same polystyrene colloid was made. The results demonstrate the importance of the nature of the anchoring moiety on the interaction of the adsorbing copolymer with the colloid surface. An endothermic contribution is found when an adsorbing molecule contains a poly (propylene oxide) (PPO) moiety (e.g. Poloxamine 908), whilst the adsorption is exothermic (i.e. enthalpy driven) for PEO copolymers with polylactide (PLA/PEG 2:5) or alkyl moieties.

Crystallization of multiple forms of bovine seminal ribonuclease in the liganded and unliganded state

NASA Astrophysics Data System (ADS)

Sica, F.; Adinolfi, S.; Berisio, R.; De Lorenzo, C.; Mazzarella, L.; Piccoli, R.; Vitagliano, L.; Zagari, A.

1999-01-01

Bovine seminal ribonuclease (BS-RNase) is an intriguing homodimeric enzyme which exists as two conformational isomers, characterized by distinct catalytic and biological properties, referred to as M×M and M=M. Reduction of inter-chain disulfide bridges produces a stable monomeric derivative (M) which is still active. This paper reports the screening and optimization of crystallization conditions for growing single diffraction-quality crystals for the various BS-RNase forms. The crystallization trials were performed using both the vapor diffusion and microbatch methods. The M×M dimer was crystallized in the free form from polyethylene glycol (PEG) 4000 at pH 8.5 and as a complex with the substrate analog uridylyl(2'- 5')guanosine (UpG) from an unbuffered ammonium sulfate (AS) solution. These two crystal types diffract X-rays to 2.5 and 1.9 Å resolution, respectively. Two different crystal types were obtained both for the M=M dimer and for the monomeric derivative. (M=M)a crystals, grown from PEG 4000 (8% w/v) at pH 5.6, diffract X-rays to 4.0 Å. At higher PEG concentration (15% w/v) a different crystal type was obtained, (M=M)b, which showed a better diffraction limit (2.5 Å). For the monomer, type (M)a and (M)b crystals, diffracting X-rays to 2.5 Å resolution, were obtained from AS at pH 6.5 and from PEG 4000 at pH 8.5, respectively. A comparison with previously crystallized forms of the dimer M×M and its complexes with uridylyl(2'-5')adenosine and 2'-deoxycytidylyl(3'-5')-2'-deoxyadenosine is also presented. The three-dimensional structure analysis of (M×M)·UpG and (M=M)b is in progress.

Preparation, characterization, and in vitro activity evaluation of triblock copolymer-based polymersomes for drugs delivery

NASA Astrophysics Data System (ADS)

Besada, Lucas N.; Peruzzo, Pablo; Cortizo, Ana M.; Cortizo, M. Susana

2018-03-01

Polymersomes are polymer-based vesicles that form upon hydration of amphiphilic block copolymers and display high stability and durability, due to their mechanical and physical properties. They have hydrophilic reservoirs as well as thick hydrophobic membranes; allowing to encapsulate both water-soluble bioactive agent and hydrophobic drugs. In this study, poly ethylene glycol (PEG3350 and PEG6000) were used as hydrophilic part and poly(vinyl benzoate) (PVBz) as hydrophobic block to synthesize amphiphilic triblock copolymers (PVBz- b-PEG- b-PVBz). Different proportions of hydrophilic/hydrophobic part were assayed in order to obtain polymersomes by solvent injection method. For the synthesis of the copolymers, the initial block of PEG was derived to obtain a macroinitiator through a xanthate functional group (PEGX3 or PEGX6) and the polymerization of vinyl benzoate was carried out through reversible addition-fragmentation chain transfer polymerization (RAFT). The structure of PEGX and copolymers was confirmed by Infrared, 1H-NMR and UV-Vis spectrometry, while the average molecular weight (Mw) and polydispersity index (PI) were determined by size exclusion chromatography (SEC). The structures adopted by the copolymers in aqueous solution by self-assembly were investigated using transmission electron microscopy (TEM), dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS). Both techniques confirm that polymersomes were obtained for a fraction of hydrophilic block ( f) ≈ 35 ± 10%, with a diameter of 38.3 ± 0.3 nm or 22.5 ± 0.7 nm, as determined by TEM and according to the M w of the precursor block copolymer. In addition, we analyzed the possible cytotoxicity in view of its potential application as biomedical nanocarrier. The results suggest that polymersomes seem not induce cytotoxicity during the periods of time tested.

Biomaterials for the Decorporation of Sr-85 in the Rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levitskaia, Tatiana G.; Creim, Jeffrey A.; Curry, Terry L.

2010-09-01

Although four stable isotopes of strontium occur naturally, strontium-90 is produced by nuclear fission and is present in surface soil around the world as a result of fallout from atmospheric nuclear weapons tests. It can easily transfer to man in the event of a nuclear/radiological emergency or through the plant-animal-human food chain causing long-term exposures. Strontium is chemically and biologically similar to calcium, and is incorporated primarily into bone following internal deposition. Alginic acid (alginate) obtained from seaweed (kelp) extract selectively binds ingested strontium in the GI tract blocking its systemic uptake and reducing distribution to bone in rats, whilemore » other natural polysaccharides including chitosan and hyaluronic acid had little in vivo affinity for strontium. Alginate exhibits the unique ability to discriminate between strontium and calcium and has been previously shown to reduce intestinal absorption and skeletal retention of strontium without changing calcium metabolism. In our studies, the effect of commercially available alginate on strontium intestinal absorption was examined. One problem associated with alginate treatment is its limited solubility and gel formation in water. The aqueous solubility of sodium alginate was improved in a sodium chloride/sodium bicarbonate electrolyte solution containing low molecular weight polyethylene glycol (PEG). Furthermore, oral administration of the combined alginate/electrolyte//PEG solution synergistically accelerated removal of internal strontium in rats when compared to treatment with individual sodium alginate/electrolyte or electrolyte/PEG solutions. Importantly, both alginate and PEG are nontoxic, readily available materials that can be easily administered orally in case of a national emergency when potentially large numbers of the population may require medical treatment for internal depositions. Our results suggest further studies to optimize in vivo decorporation performance of engineered alginate material via modification of its chemical and physicochemical properties is warranted.« less

Detection methods for human enteric viruses in representative foods.

PubMed

Leggitt, P R; Jaykus, L A

2000-12-01

Although viral foodborne disease is a significant problem, foods are rarely tested for viral contamination, and when done, testing is limited to shellfish commodities. In this work, we report a method to extract and detect human enteric viruses from alternative food commodities using an elution-concentration approach followed by detection using reverse transcription-polymerase chain reaction (RT-PCR). Fifty-gram lettuce or hamburger samples were artificially inoculated with poliovirus type 1 (PV1), hepatitis A virus (HAV), or the Norwalk virus and processed by the sequential steps of homogenization, filtration, Freon extraction (hamburger), and polyethylene glycol (PEG) precipitation. To reduce volumes further and remove RT-PCR inhibitors, a secondary PEG precipitation was necessary, resulting in an overall 10- to 20-fold sample size reduction from 50 g to 3 to 5 ml. Virus recoveries in secondary PEG concentrates ranged from 10 to 70% for PV1 and 2 to 4% for HAV as evaluated by mammalian cell culture infectivity assay. Total RNA from PEG concentrates was extracted to a small volume (30 to 40 microl) and subjected to RT-PCR amplification of viral RNA sequences. Detection limit studies indicated that viral RNA was consistently detected by RT-PCR at initial inoculum levels > or =102 PFU/50-g food sample for PV1 and > or =10(3) PFU/50-g food sample for HAV. In similar studies with the Norwalk virus, detection at inoculum levels > or =1.5 X 10(3) PCR-amplifiable units/50-g sample for both food products was possible. All RT-PCR amplicons were confirmed by subsequent Southern hybridization. The procedure reported represents progress toward the development of methods to detect human enteric viral contamination in foods other than shellfish.

Amphiphilic Ferrocene-Containing PEG Block Copolymers as Micellar Nanocarriers and Smart Surfactants.

PubMed

Alkan, Arda; Wald, Sarah; Louage, Benoit; De Geest, Bruno G; Landfester, Katharina; Wurm, Frederik R

2017-01-10

An important and usually the only function of most surfactants in heterophase systems is stabilizing one phase in another, for example, droplets or particles in water. Surfactants with additional chemical or physical handles are promising in controlling the colloidal properties by external stimuli. The redox stimulus is an attractive feature; however, to date only a few ionic redox-responsive surfactants have been reported. Herein, the first nonionic and noncytotoxic ferrocene-containing block copolymers are prepared, carrying a hydrophilic poly(ethylene glycol) (PEG) chain and multiple ferrocenes in the hydrophobic segment. These amphiphiles were studied as redox-sensitive surfactants that destabilize particles as obtained in miniemulsion polymerization. Because of the nonionic nature of such PEG-based copolymers, they can stabilize nanoparticles even after the addition of ions, whereas particles stabilized with ionic surfactants would be destabilized by the addition of salt. The redox-active surfactants were prepared by the anionic ring-opening polymerization of ferrocenyl glycidyl ether, with PEG monomethyl ether as the macroinitiator. The resultant block copolymers with molecular weights (M n ) between 3600 and 8600 g mol -1 and narrow molecular weight distributions (M w /M n = 1.04-1.10) were investigated via 1 H nuclear magnetic resonance and diffusion ordered spectroscopy, size exclusion chromatography, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Furthermore, the block copolymers were used as building blocks for redox-responsive micelles and as redox-responsive surfactants in radical polymerization in miniemulsion to stabilize model polystyrene nanoparticles. Oxidation of iron to the ferrocenium species converted the amphiphilic block copolymers into double hydrophilic macromolecules, which led to the destabilization of the nanoparticles. This destabilization of nanoparticle dispersions may be useful for the formation of coatings and the recovery of surfactants.

Conformation transitions of a single polyelectrolyte chain in a poor solvent: a replica-exchange lattice Monte-Carlo study.

PubMed

Wang, Lang; Wang, Zheng; Jiang, Run; Yin, Yuhua; Li, Baohui

2017-03-15

The thermodynamic behaviors of a strongly charged polyelectrolyte chain in a poor solvent are studied using replica-exchange Monte-Carlo simulations on a lattice model, focusing on the effects of finite chain length and the solvent quality on the chain conformation and conformation transitions. The neutralizing counterions and solvent molecules are considered explicitly. The thermodynamic quantities that vary continuously with temperature over a wide range are computed using the multiple histogram reweighting method. Our results suggest that the strength of the short-range hydrophobic interaction, the chain length, and the temperature of the system, characterized by ε, N, and T, respectively, are important parameters that control the conformations of a charged chain. When ε is moderate, the competition between the electrostatic energy and the short-range hydrophobic interaction leads to rich conformations and conformation transitions for a longer chain with a fixed length. Our results have unambiguously demonstrated the stability of the n-pearl-necklace structures, where n has a maximum value and decreases with decreasing temperature. The maximum n value increases with increasing chain length. Our results have also demonstrated the first-order nature of the conformation transitions between the m-pearl and the (m-1)-pearl necklaces. With the increase of ε, the transition temperature increases and the first-order feature becomes more pronounced. It is deduced that at the thermodynamic limit of infinitely long chain length, the conformational transitions between the m-pearl and the (m-1)-pearl necklaces may remain first order when ε > 0 and m = 2 or 3. Pearl-necklace conformations cannot be observed when either ε is too large or N is too small. To observe a pearl-necklace conformation, the T value needs to be carefully chosen for simulations performed at only a single temperature.

Effect of PEG-PDLLA polymeric nanovesicles loaded with doxorubicin and hematoporphyrin monomethyl ether on human hepatocellular carcinoma HepG2 cells in vitro.

PubMed

Xiang, Guang-Hua; Hong, Guo-Bin; Wang, Yong; Cheng, Du; Zhou, Jing-Xing; Shuai, Xin-Tao

2013-01-01

To evaluate the cytotoxicity of poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-PDLLA) nanovesicles loaded with doxorubicin (DOX) and the photosensitizer hematoporphyrin monomethyl ether (HMME) on human hepatocellular carcinoma HepG2 cells and to investigate potential apoptotic mechanisms. PEG-PDLLA nanovesicles were simultaneously loaded with DOX and HMME (PEG-PDLLA-DOX-HMME), and PEG-PDLLA nanovesicles were loaded with DOX (PEG-PDLLA-DOX), HMME (PEG-PDLLA-HMME), or the PEG-PDLLA nanovesicle alone as controls. The cytotoxicity of PEG-PDLLA-DOX-HMME, PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA against HepG2 cells was measured, and the cellular reactive oxygen species, percentage of cells with mitochondrial membrane potential depolarization, and apoptotic rate following treatment were determined. Four nanovesicles (PEG-PDLLA-DOX-HMME, PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA) were synthesized, and mean particle sizes were 175±18 nm, 154±3 nm, 196±2 nm, and 147±15 nm, respectively. PEG-PDLLA-DOX-HMME was more cytotoxic than PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA. PEG-PDLLA-HMME-treated cells had the highest mean fluorescence intensity, followed by PEG-PDLLA-DOX-HMME-treated cells, whereas PEG-PDLLA-DOX- and PEG-PDLLA-treated cells had a similar fluorescence intensity. Mitochondrial membrane potential depolarization was observed in 54.2%, 59.4%, 13.8%, and 14.8% of the cells treated with PEG-PDLLA-DOX-HMME, PEG-PDLLA-HMME, PEG-PDLLA-DOX, and PEG-PDLLA, respectively. The apoptotic rate was significantly higher in PEG-PDLLA-DOX-HMME-treated cells compared with PEG-PDLLA-DOX- and PEG-PDLLA-HMME-treated cells. The PEG-PDLLA nanovesicle, a drug delivery carrier, can be simultaneously loaded with two anticancer drugs (hydrophilic DOX and hydrophobic HMME). PEG-PDLLA-DOX-HMME cytotoxicity to HepG2 cells is significantly higher than the PEG-PDLLA nanovesicle loaded with DOX or HMME alone, and DOX and HMME have a synergistic effect against human hepatocellular carcinoma HepG2 cells.

Light, nutrients, and food-chain length constrain planktonic energy transfer efficiency across multiple trophic levels

PubMed Central

Dickman, Elizabeth M.; Newell, Jennifer M.; González, María J.; Vanni, Michael J.

2008-01-01

The efficiency of energy transfer through food chains [food chain efficiency (FCE)] is an important ecosystem function. It has been hypothesized that FCE across multiple trophic levels is constrained by the efficiency at which herbivores use plant energy, which depends on plant nutritional quality. Furthermore, the number of trophic levels may also constrain FCE, because herbivores are less efficient in using plant production when they are constrained by carnivores. These hypotheses have not been tested experimentally in food chains with 3 or more trophic levels. In a field experiment manipulating light, nutrients, and food-chain length, we show that FCE is constrained by algal food quality and food-chain length. FCE across 3 trophic levels (phytoplankton to carnivorous fish) was highest under low light and high nutrients, where algal quality was best as indicated by taxonomic composition and nutrient stoichiometry. In 3-level systems, FCE was constrained by the efficiency at which both herbivores and carnivores converted food into production; a strong nutrient effect on carnivore efficiency suggests a carryover effect of algal quality across 3 trophic levels. Energy transfer efficiency from algae to herbivores was also higher in 2-level systems (without carnivores) than in 3-level systems. Our results support the hypothesis that FCE is strongly constrained by light, nutrients, and food-chain length and suggest that carryover effects across multiple trophic levels are important. Because many environmental perturbations affect light, nutrients, and food-chain length, and many ecological services are mediated by FCE, it will be important to apply these findings to various ecosystem types. PMID:19011082

cDNA cloning and characterization of Type I procollagen alpha1 chain in the skate Raja kenojei.

PubMed

Hwang, Jae-Ho; Yokoyama, Yoshihiro; Mizuta, Shoshi; Yoshinaka, Reiji

2006-05-01

A full-length cDNA of the Type I procollagen alpha1 [pro-alpha1(I)] chain (4388 bp), coding for 1463 amino acid residues in the total length, was determined by RACE PCR using a cDNA library constructed from 4-week embryo of the skate Raja kenojei. The helical region of the skate pro-alpha1(I) chain consisted of 1014 amino acid residues - the same as other fibrillar collagen alpha chains from higher vertebrates. Comparison on denaturation temperatures of Type I collagens from the skate, rainbow trout (Oncorhynchus mykiss) and rat (Rattus norvegicus) revealed that the number of Gly-Pro-Pro and Gly-Gly in the alpha1(I) chains could be directly related to the thermal stability of the helix. The expression property of the skate pro-alpha1(I) chain mRNA and phylogenetic analysis with other vertebrate pro-alpha1(I) chains suggested that skate pro-alpha1(I) chain could be a precursor form of the skate Type I collagen alpha1 chain. The present study is the first evidence for the primary structure of full-length pro-alpha1(I) chain in an elasmobranch.

Broken Chains and Reneging: A Review of 1748 Kidney Paired Donation Transplants.

PubMed

Cowan, N; Gritsch, H A; Nassiri, N; Sinacore, J; Veale, J

2017-09-01

Concerns regarding the potential for broken chains and "reneges" within kidney paired donation (KPD) and its effect on chain length have been raised previously. Although these concerns have been tested in simulation studies, real-world data have yet to be evaluated. The purpose of this study was to evaluate the actual rate and causes of broken chains within a large KPD program. All patients undergoing renal transplantation through the National Kidney Registry from 2008 through May 2016 were included for analysis. Broken chains and loops were identified. A total of 344 chains and 78 loops were completed during the study period, yielding a total of 1748 transplants. Twenty broken chains and one broken loop were identified. The mean chain length (number of transplants) within broken chains was 4.8 compared with 4.6 of completed chains (p = 0.78). The most common causes of a broken chain were donor medical issues incurred while acting as a bridge donor (n = 8), donors electing not to proceed (n = 6), and kidneys being declined by the recipient surgeon (n = 4). All recipients involved in a broken chain subsequently received a transplant. Based on the results, broken chains are infrequent, are rarely due to lack of donor motivation, and have no significant impact on chain length. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

The importance of chain length for the polyphosphate enhancement of acidic potassium permanganate chemiluminescence.

PubMed

Holland, Brendan J; Adcock, Jacqui L; Nesterenko, Pavel N; Peristyy, Anton; Stevenson, Paul G; Barnett, Neil W; Conlan, Xavier A; Francis, Paul S

2014-09-09

Sodium polyphosphate is commonly used to enhance chemiluminescence reactions with acidic potassium permanganate through a dual enhancement mechanism, but commercially available polyphosphates vary greatly in composition. We have examined the influence of polyphosphate composition and concentration on both the dual enhancement mechanism of chemiluminescence intensity and the stability of the reagent under analytically useful conditions. The average chain length (n) provides a convenient characterisation, but materials with similar values can exhibit markedly different distributions of phosphate oligomers. There is a minimum polyphosphate chain length (∼6) required for a large enhancement of the emission intensity, but no further advantage was obtained using polyphosphate materials with much longer average chain lengths. Providing there is a sufficient average chain length, the optimum concentration of polyphosphate is dependent on the analyte and in some cases, may be lower than the quantities previously used in routine detection. However, the concentration of polyphosphate should not be lowered in permanganate reagents that have been partially reduced to form high concentrations of the key manganese(III) co-reactant, as this intermediate needs to be stabilised to prevent formation of insoluble manganese(IV). Copyright © 2014 Elsevier B.V. All rights reserved.

Chain length effects of p-oligophenyls with comparison of benzene by Raman scattering

NASA Astrophysics Data System (ADS)

Zhang, Kai; Chen, Xiao-Jia

2018-02-01

Raman scattering measurements are performed on benzene and a number of p-oligophenyls including biphenyl, p-terphenyl, p-quaterphenyl, p-quinquephenyl, and p-sexiphenyl at ambient conditions. The vibrational modes of the intra- and intermolecular terms in these materials are analyzed and compared. Chain length effects on the vibrational properties are examined for the C-H in-plane bending mode and the inter-ring C-C stretching mode at around 1200 cm-1 and 1280 cm-1, respectively, and the C-C stretching modes at around 1600 cm-1. The complex and fluctuating properties of these modes result in an imprecise estimation of the chain length of these molecules. Meanwhile, the obtained ratio of the intensities of the 1200 cm-1 mode and 1280 cm-1 mode is sensitive to the applied lasers. A librational motion mode with the lowest energy is found to have a monotonous change with the increase in the chain length. This mode is simply relevant to the c axis of the unit cell. Such an obvious trend makes it a better indicator for determining the chain length effects on the physical and chemical properties in these molecules.

Biodegradable hyperbranched amphiphilic polyurethane multiblock copolymers consisting of poly(propylene glycol), poly(ethylene glycol), and polycaprolactone as in situ thermogels.

PubMed

Li, Zibiao; Zhang, Zhongxing; Liu, Kerh Li; Ni, Xiping; Li, Jun

2012-12-10

This paper reports the synthesis and characterization of new hyperbranched amphiphilic polyurethane multiblock copolymers consisting of poly(propylene glycol) (PPG), poly(ethylene glycol) (PEG), and polycaprolactone (PCL) segments as in situ thermogels. The hyperbranched poly(PPG/PEG/PCL urethane)s, termed as HBPEC copolymers, were synthesized from PPG-diol, PEG-diol, and PCL-triol by using 1,6-hexamethylene diisocyanate (HMDI) as a coupling agent. The compositions and structures of HBPEC copolymers were determined by GPC and 1H NMR spectroscopy. We carried out comparative studies of the new hyperbranched copolymers with their linear counterparts, the linear poly(PPG/PEG/PCL urethane) (LPEC) copolymer and Pluronic F127 PEG-PPG-PEG block copolymer, in terms of their self-assembly and aggregation behaviors and thermoresponsive properties. HBPEC copolymers were found to show thermoresponsive micelle formation and aggregation behaviors. Particularly, the lower critical solution temperature (LCST) of the copolymers was significantly affected by the copolymer architecture. HBPEC copolymers showed much lower LCST than LPEC, the linear counterpart. Our studies revealed that the effect of hyperbranch architecture was more prominent in the gelation of the copolymers. The aqueous solutions of HBPEC copolymers exhibited thermogelling behaviors at critical gelation concentrations (CGCs) ranging from 4.3 to 7.4 wt %. These values are much lower than those reported on other PCL-contained linear thermogelling copolymers and Pluronic F127 copolymer. In addition, the CGC of HBPEC copolymers is much lower than the control LPEC copolymer. More interestingly, at high temperatures, while LPEC and other linear thermogelling copolymers formed turbid sol, HBPEC formed a dehydrated gel. Our data suggest that these phenomena are caused by the hyperbranched structure of HBPEC copolymers, which could increase the interaction of copolymer branches and enhance the chain association through synergetic hydrogen bonding effect. The thermogelling behavior of HBPEC block copolymers was further evidenced by the 1H NMR molecular dynamic study and rheological study, which further support the above hypothesis. The hydrolytic degradation study showed that the HBPEC copolymer hydrogels are biodegradable under physiological conditions. Together with the good cell biocompatibility demonstrated by the cytotoxicity study, the new thermogelling copolymers reported in this paper could potentially be used as in situ-forming hydrogels for biomedical applications.

Tracking hypoxic signaling within encapsulated cell aggregates.

PubMed

Skiles, Matthew L; Sahai, Suchit; Blanchette, James O

2011-12-16

In Diabetes mellitus type 1, autoimmune destruction of the pancreatic β-cells results in loss of insulin production and potentially lethal hyperglycemia. As an alternative treatment option to exogenous insulin injection, transplantation of functional pancreatic tissue has been explored. This approach offers the promise of a more natural, long-term restoration of normoglycemia. Protection of the donor tissue from the host's immune system is required to prevent rejection and encapsulation is a method used to help achieve this aim. Biologically-derived materials, such as alginate and agarose, have been the traditional choice for capsule construction but may induce inflammation or fibrotic overgrowth which can impede nutrient and oxygen transport. Alternatively, synthetic poly(ethylene glycol) (PEG)-based hydrogels are non-degrading, easily functionalized, available at high purity, have controllable pore size, and are extremely biocompatible. As an additional benefit, PEG hydrogels may be formed rapidly in a simple photo-crosslinking reaction that does not require application of non-physiological temperatures. Such a procedure is described here. In the crosslinking reaction, UV degradation of the photoinitiator, 1-[4-(2-Hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-1-propane-1-one (Irgacure 2959), produces free radicals which attack the vinyl carbon-carbon double bonds of dimethacrylated PEG (PEGDM) inducing crosslinking at the chain ends. Crosslinking can be achieved within 10 minutes. PEG hydrogels constructed in such a manner have been shown to favorably support cells, and the low photoinitiator concentration and brief exposure to UV irradiation is not detrimental to viability and function of the encapsulated tissue. While we methacrylate our PEG with the method described below, PEGDM can also be directly purchased from vendors such as Sigma. An inherent consequence of encapsulation is isolation of the cells from a vascular network. Supply of nutrients, notably oxygen, is therefore reduced and limited by diffusion. This reduced oxygen availability may especially impact β-cells whose insulin secretory function is highly dependent on oxygen. Capsule composition and geometry will also impact diffusion rates and lengths for oxygen. Therefore, we also describe a technique for identifying hypoxic cells within our PEG capsules. Infection of the cells with a recombinant adenovirus allows for a fluorescent signal to be produced when intracellular hypoxia-inducible factor (HIF) pathways are activated. As HIFs are the primary regulators of the transcriptional response to hypoxia, they represent an ideal target marker for detection of hypoxic signaling. This approach allows for easy and rapid detection of hypoxic cells. Briefly, the adenovirus has the sequence for a red fluorescent protein (Ds Red DR from Clontech) under the control of a hypoxia-responsive element (HRE) trimer. Stabilization of HIF-1 by low oxygen conditions will drive transcription of the fluorescent protein (Figure 1). Additional details on the construction of this virus have been published previously. The virus is stored in 10% glycerol at -80° C as many 150 μL aliquots in 1.5 mL centrifuge tubes at a concentration of 3.4 x 10(10) pfu/mL. Previous studies in our lab have shown that MIN6 cells encapsulated as aggregates maintain their viability throughout 4 weeks of culture in 20% oxygen. MIN6 aggregates cultured at 2 or 1% oxygen showed both signs of necrotic cells (still about 85-90% viable) by staining with ethidium bromide as well as morphological changes relative to cells in 20% oxygen. The smooth spherical shape of the aggregates displayed at 20% was lost and aggregates appeared more like disorganized groups of cells. While the low oxygen stress does not cause a pronounced drop in viability, it is clearly impacting MIN6 aggregation and function as measured by glucose-stimulated insulin secretion. Western blot analysis of encapsulated cells in 20% and 1% oxygen also showed a significant increase in HIF-1α for cells cultured in the low oxygen conditions which correlates with the expression of the DsRed DR protein.

Colloidal Mechanisms of Gold Nanoparticle Loss in Asymmetric Flow Field-Flow Fractionation.

PubMed

Jochem, Aljosha-Rakim; Ankah, Genesis Ngwa; Meyer, Lars-Arne; Elsenberg, Stephan; Johann, Christoph; Kraus, Tobias

2016-10-07

Flow field-flow fractionation is a powerful method for the analysis of nanoparticle size distributions, but its widespread use has been hampered by large analyte losses, especially of metal nanoparticles. Here, we report on the colloidal mechanisms underlying the losses. We systematically studied gold nanoparticles (AuNPs) during asymmetrical flow field-flow fractionation (AF4) by systematic variation of the particle properties and the eluent composition. Recoveries of AuNPs (core diameter 12 nm) stabilized by citrate or polyethylene glycol (PEG) at different ionic strengths were determined. We used online UV-vis detection and off-line elementary analysis to follow particle losses during full analysis runs, runs without cross-flow, and runs with parts of the instrument bypassed. The combination allowed us to calculate relative and absolute analyte losses at different stages of the analytic protocol. We found different loss mechanisms depending on the ligand. Citrate-stabilized particles degraded during analysis and suffered large losses (up to 74%). PEG-stabilized particles had smaller relative losses at moderate ionic strengths (1-20%) that depended on PEG length. Long PEGs at higher ionic strengths (≥5 mM) caused particle loss due to bridging adsorption at the membrane. Bulk agglomeration was not a relevant loss mechanism at low ionic strengths ≤5 mM for any of the studied particles. An unexpectedly large fraction of particles was lost at tubing and other internal surfaces. We propose that the colloidal mechanisms observed here are relevant loss mechanisms in many particle analysis protocols and discuss strategies to avoid them.

Nanotechnology-Enabled Optical Molecular Imaging of Breast Cancer

DTIC Science & Technology

2010-07-01

Abbreviations Ab antibody AF-Ab Alexa Fluor labeled antibody CCD charge coupled device CTAB cetyltrimethylammonium bromide EDC 1-ethyl-[3-dimethylaminopropyl...mPEG-SH in figure 1. The carboxy-terminal nanorods were conjugated to antibodies using the zero-length crosslinker EDC stabilized by NHS [38]. Standard...multimode fiber coupler /positioner (Newport, model: F-915T) is utilized to mount the objective lens and a fiber chuck (Newport, model: FPH-DJ). With

The cellular level of O-antigen polymerase Wzy determines chain length regulation by WzzB and WzzpHS-2 in Shigella flexneri 2a.

PubMed

Carter, Javier A; Jiménez, Juan C; Zaldívar, Mercedes; Alvarez, Sergio A; Marolda, Cristina L; Valvano, Miguel A; Contreras, Inés

2009-10-01

The lipopolysaccharide O antigen of Shigella flexneri 2a has two preferred chain lengths, a short (S-OAg) composed of an average of 17 repeated units and a very long (VL-OAg) of about 90 repeated units. These chain length distributions are controlled by the chromosomally encoded WzzB and the plasmid-encoded Wzz(pHS-2) proteins, respectively. In this study, genes wzzB, wzz(pHS-2) and wzy (encoding the O-antigen polymerase) were cloned under the control of arabinose- and rhamnose-inducible promoters to investigate the effect of varying their relative expression levels on O antigen polysaccharide chain length distribution. Controlled expression of the chain length regulators wzzB and wzz(pHS-2) revealed a dose-dependent production of each modal length. Increase in one mode resulted in a parallel decrease in the other, indicating that chain length regulators compete to control the degree of O antigen polymerization. Also, when expression of the wzy gene is low, S-OAg but not VL-OAg is produced. Production of VL-OAg requires high induction levels of wzy. Thus, the level of expression of wzy is critical in determining O antigen modal distribution. Western blot analyses of membrane proteins showed comparable high levels of the WzzB and Wzz(pHS-2) proteins, but very low levels of Wzy. In vivo cross-linking experiments and immunoprecipitation of membrane proteins did not detect any direct interaction between Wzy and WzzB, suggesting the possibility that these two proteins may not interact physically but rather by other means such as via translocated O antigen precursors.

ε-Poly-l-Lysine Peptide Chain Length Regulated by the Linkers Connecting the Transmembrane Domains of ε-Poly-l-Lysine Synthetase

PubMed Central

Kito, Naoko; Kita, Akihiro; Imokawa, Yuuki; Yamanaka, Kazuya; Maruyama, Chitose; Katano, Hajime

2014-01-01

ε-Poly-l-lysine (ε-PL), consisting of 25 to 35 l-lysine residues with linkages between the α-carboxyl groups and ε-amino groups, is produced by Streptomyces albulus NBRC14147. ε-PL synthetase (Pls) is a membrane protein with six transmembrane domains (TM1 to TM6) as well as both an adenylation domain and a thiolation domain, characteristic of the nonribosomal peptide synthetases. Pls directly generates ε-PL chain length diversity (25- to 35-mer), but the processes that control the chain length of ε-PL during the polymerization reaction are still not fully understood. Here, we report on the identification of Pls amino acid residues involved in the regulation of the ε-PL chain length. From approximately 12,000 variants generated by random mutagenesis, we found 8 Pls variants that produced shorter chains of ε-PL. These variants have one or more mutations in two linker regions connecting the TM1 and TM2 domains and the TM3 and TM4 domains. In the Pls catalytic mechanism, the growing chain of ε-PL is not tethered to the enzyme, implying that the enzyme must hold the growing chain until the polymerization reaction is complete. Our findings reveal that the linker regions are important contributors to grasp the growing chain of ε-PL. PMID:24907331

Monte Carlo simulations of lattice models for single polymer systems

NASA Astrophysics Data System (ADS)

Hsu, Hsiao-Ping

2014-10-01

Single linear polymer chains in dilute solutions under good solvent conditions are studied by Monte Carlo simulations with the pruned-enriched Rosenbluth method up to the chain length N ˜ O(10^4). Based on the standard simple cubic lattice model (SCLM) with fixed bond length and the bond fluctuation model (BFM) with bond lengths in a range between 2 and sqrt{10}, we investigate the conformations of polymer chains described by self-avoiding walks on the simple cubic lattice, and by random walks and non-reversible random walks in the absence of excluded volume interactions. In addition to flexible chains, we also extend our study to semiflexible chains for different stiffness controlled by a bending potential. The persistence lengths of chains extracted from the orientational correlations are estimated for all cases. We show that chains based on the BFM are more flexible than those based on the SCLM for a fixed bending energy. The microscopic differences between these two lattice models are discussed and the theoretical predictions of scaling laws given in the literature are checked and verified. Our simulations clarify that a different mapping ratio between the coarse-grained models and the atomistically realistic description of polymers is required in a coarse-graining approach due to the different crossovers to the asymptotic behavior.

Comparison studies of rheological and thermal behaviors of ionic liquids and nanoparticle ionic liquids.

PubMed

Xu, Yiting; Zheng, Qiang; Song, Yihu

2015-08-14

Novel nanoparticle ionic liquids (NILs) are prepared by grafting modified nanoparticles with long-chain ionic liquids (ILs). The NIL behaves like a liquid at ambient temperature. We studied the rheological behavior of the IL and NIL over the range of 10-55 °C and found an extraordinary difference between the IL and NIL: a small content of nanosilica (7%) moderately improves the crystallinity by 7% of the poly(ethylene glycol) (PEG) segment in the IL, and it improves the dynamic moduli significantly (by 5 times at room temperature). It retards the decay temperature (by 10 °C) of the dynamic moduli during heating as well. The thermal rheological hysteresis observed during heating-cooling temperature sweeps is ascribed to the melting-recrystallization of the PEG segments. Meanwhile, the IL and NIL express accelerated crystallization behavior in comparison with the oligomeric anion. For the first time, we find that ILs and NILs are able to form nanoparticle-containing spherulites at room temperature after long time aging.

Synthesis, Amphiphilic Property and Thermal Stability of Novel Main-chain Poly(o-carborane-benzoxazines)

NASA Astrophysics Data System (ADS)

Yang, Xiaoxue; Han, Guo; Yang, Zhen; Zhang, Xiaoa; Jiang, Shengling; Lyu, Yafei

2017-10-01

Five poly(o-carborane-benzoxazines) were synthesized via Mannich reaction of o-carborane bisphenol, paraformaldehyde, and diamine, and their structures were well characterized. Light transmission and 1H NMR in D2O confirmed that poly(o-carborane-benzoxazines) with PEG segments showed excellent water solubility and amphiphilic property. TGA analyses were conducted under nitrogen and air, and the results showed that the polymers own high initial decomposition temperatures owing to the shielding effect of carborane moiety on its adjacent aromatic structures. Besides, poly(o-carborane-benzoxazines) own high char yield at elevated temperatures, for the boron atom could combine with oxygen from the polymer structure or/and the air and be oxidized to form boron oxide, and thus the polymer weight is retained to a large extent. PEG segments had an adverse effect on the initial decomposition and char yield, and thus their concentration should be adjusted to control the polymer’s thermal stability.

Additives for vaccine storage to improve thermal stability of adenoviruses from hours to months

NASA Astrophysics Data System (ADS)

Pelliccia, Maria; Andreozzi, Patrizia; Paulose, Jayson; D'Alicarnasso, Marco; Cagno, Valeria; Donalisio, Manuela; Civra, Andrea; Broeckel, Rebecca M.; Haese, Nicole; Jacob Silva, Paulo; Carney, Randy P.; Marjomäki, Varpu; Streblow, Daniel N.; Lembo, David; Stellacci, Francesco; Vitelli, Vincenzo; Krol, Silke

2016-11-01

Up to 80% of the cost of vaccination programmes is due to the cold chain problem (that is, keeping vaccines cold). Inexpensive, biocompatible additives to slow down the degradation of virus particles would address the problem. Here we propose and characterize additives that, already at very low concentrations, improve the storage time of adenovirus type 5. Anionic gold nanoparticles (10-8-10-6 M) or polyethylene glycol (PEG, molecular weight ~8,000 Da, 10-7-10-4 M) increase the half-life of a green fluorescent protein expressing adenovirus from ~48 h to 21 days at 37 °C (from 7 to >30 days at room temperature). They replicate the known stabilizing effect of sucrose, but at several orders of magnitude lower concentrations. PEG and sucrose maintained immunogenicity in vivo for viruses stored for 10 days at 37 °C. To achieve rational design of viral-vaccine stabilizers, our approach is aided by simplified quantitative models based on a single rate-limiting step.

Injectable hyperbranched poly(β-amino ester) hydrogels with on-demand degradation profiles to match wound healing processes† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc03913a

PubMed Central

Xu, Qian; Guo, Linru; A, Sigen; Gao, Yongsheng; Zhou, Dezhong; Greiser, Udo; Creagh-Flynn, Jack; Zhang, Hong; Dong, Yixiao; Cutlar, Lara; Wang, Fagang; Liu, Wenguang

2018-01-01

Adjusting biomaterial degradation profiles to match tissue regeneration is a challenging issue. Herein, biodegradable hyperbranched poly(β-amino ester)s (HP-PBAEs) were designed and synthesized via “A2 + B4” Michael addition polymerization, and displayed fast gelation with thiolated hyaluronic acid (HA-SH) via a “click” thiol–ene reaction. HP-PBAE/HA-SH hydrogels showed tunable degradation profiles both in vitro and in vivo using diamines with different alkyl chain lengths and poly(ethylene glycol) diacrylates with varied PEG spacers. The hydrogels with optimized degradation profiles encapsulating ADSCs were used as injectable hydrogels to treat two different types of humanized excisional wounds – acute wounds with faster healing rates and diabetic wounds with slower healing and neo-tissue formation. The fast-degrading hydrogel showed accelerated wound closure in acute wounds, while the slow-degrading hydrogel showed better wound healing for diabetic wounds. The results demonstrate that the new HP-PBAE-based hydrogel in combination with ADSCs can be used as a well-controlled biodegradable skin substitute, which demonstrates a promising approach in the treatment of various types of skin wounds. PMID:29719691

Role of the Methoxy Group in Immune Responses to mPEG-Protein Conjugates

PubMed Central

2012-01-01

Anti-PEG antibodies have been reported to mediate the accelerated clearance of PEG-conjugated proteins and liposomes, all of which contain methoxyPEG (mPEG). The goal of this research was to assess the role of the methoxy group in the immune responses to mPEG conjugates and the potential advantages of replacing mPEG with hydroxyPEG (HO-PEG). Rabbits were immunized with mPEG, HO-PEG, or t-butoxyPEG (t-BuO-PEG) conjugates of human serum albumin, human interferon-α, or porcine uricase as adjuvant emulsions. Assay plates for enzyme-linked immunosorbent assays (ELISAs) were coated with mPEG, HO-PEG, or t-BuO-PEG conjugates of the non-cross-reacting protein, porcine superoxide dismutase (SOD). In sera from rabbits immunized with HO-PEG conjugates of interferon-α or uricase, the ratio of titers of anti-PEG antibodies detected on mPEG-SOD over HO-PEG-SOD (“relative titer”) had a median of 1.1 (range 0.9–1.5). In contrast, sera from rabbits immunized with mPEG conjugates of three proteins had relative titers with a median of 3.0 (range 1.1–20). Analyses of sera from rabbits immunized with t-BuO-PEG-albumin showed that t-butoxy groups are more immunogenic than methoxy groups. Adding Tween 20 or Tween 80 to buffers used to wash the assay plates, as is often done in ELISAs, greatly reduced the sensitivity of detection of anti-PEG antibodies. Competitive ELISAs revealed that the affinities of antibodies raised against mPEG-uricase were c. 70 times higher for 10 kDa mPEG than for 10 kDa PEG diol and that anti-PEG antibodies raised against mPEG conjugates of three proteins had >1000 times higher affinities for albumin conjugates with c. 20 mPEGs than for analogous HO-PEG-albumin conjugates. Overall, these results are consistent with the hypothesis that antibodies with high affinity for methoxy groups contribute to the loss of efficacy of mPEG conjugates, especially if multiply-PEGylated. Using monofunctionally activated HO-PEG instead of mPEG in preparing conjugates for clinical use might decrease this undesirable effect. PMID:22332808

Microphase separation of comb copolymers with two different lengths of side chains

NASA Astrophysics Data System (ADS)

Aliev, M. A.; Kuzminyh, N. Yu.

2009-10-01

The phase behavior of the monodisperse AB comb copolymer melt contained the macromolecules of special architecture is discussed. Each macromolecule is assumed to be composed of two comb blocks which differ in numbers of side chains and numbers of monomer units in these chains. It is shown (by analysis of the structure factor of the melt) that microphase separation at two different length scales in the melt is possible. The large and small length scales correspond to separation between comb blocks and separation between monomer units in repeating fragments of blocks, respectively. The classification diagrams indicated which length scale is favored for a given parameters of chemical structure of macromolecules are constructed.

Binary release of ascorbic acid and lecithin from core-shell nanofibers on blood-contacting surface for reducing long-term hemolysis of erythrocyte.

PubMed

Shi, Qiang; Fan, Qunfu; Ye, Wei; Hou, Jianwen; Wong, Shing-Chung; Xu, Xiaodong; Yin, Jinghua

2015-01-01

There is an urgent need to develop blood-contacting biomaterials with long-term anti-hemolytic capability. To obtain such biomaterials, we coaxially electrospin [ascorbic acid (AA) and lecithin]/poly (ethylene oxide) (PEO) core-shell nanofibers onto the surface of styrene-b-(ethylene-co-butylene)-b-styrene elastomer (SEBS) that has been grafted with poly (ethylene glycol) (PEG) chains. Our strategy is based on that the grafted layers of PEG render the surface hydrophilic to reduce the mechanical injure to red blood cells (RBCs) while the AA and lecithin released from nanofibers on blood-contacting surface can actively interact with RBCs to decrease the oxidative damage to RBCs. We demonstrate that (AA and lecithin)/PEO core-shell structured nanofibers have been fabricated on the PEG grafted surface. The binary release of AA and lecithin in the distilled water is in a controlled manner and lasts for almost 5 days; during RBCs preservation, AA acts as an antioxidant and lecithin as a lipid supplier to the membrane of erythrocytes, resulting in low mechanical fragility and hemolysis of RBCs, as well as high deformability of stored RBCs. Our work thus makes a new approach to fabricate blood-contacting biomaterials with the capability of long-term anti-hemolysis. Copyright © 2014 Elsevier B.V. All rights reserved.

Controllable synthesis of a novel magnetic core-shell nanoparticle for dual-modal imaging and pH-responsive drug delivery

NASA Astrophysics Data System (ADS)

Xu, Chen; Zhang, Cheng; Wang, Yingxi; Li, Liu; Li, Ling; Whittaker, Andrew K.

2017-12-01

In this study, novel magnetic core-shell nanoparticles Fe3O4@La-BTC/GO have been synthesized by the layer-by-layer self-assembly (LBL) method and further modified by attachment of amino-modified PEG chains. The nanoparticles were thoroughly characterized by x-ray diffraction, FTIR, scanning electron microscopy and transmission electron microscopy. The core-shell structure was shown to be controlled by the LBL method. The drug loading of doxorubicin (DOX) within the Fe3O4@La-BTC/GO-PEG nanoparticles with different numbers of deposited layers was investigated. It was found that DOX loading increased with increasing number of metal organic framework coating layers, indicating that the drug loading can be controlled through the controllable LBL method. Cytotoxicity assays indicated that the Fe3O4@La-BTC/GO-PEG nanoparticles were biocompatible. The DOX was released rapidly at pH 3.8 and pH 5.8, but at pH 7.4 the rate and extent of release was greatly attenuated. The nanoparticles therefore demonstrate an excellent pH-triggered drug release. In addition, the particles could be tracked by magnetic resonance imaging (MRI) and fluorescence optical imaging (FOI). A clear dose-dependent contrast enhancement in T 2-weighted MR images and fluorescence images indicate the potential of these nanoparticles as dual-mode MRI/FOI contrast agents.

The mPEG-PCL Copolymer for Selective Fermentation of Staphylococcus lugdunensis Against Candida parapsilosis in the Human Microbiome

PubMed Central

Kao, Ming-Shan; Wang, Yanhan; Marito, Shinta; Huang, Stephen; Lin, Wan-Zhen; Gangoiti, Jon A; Barshop, Bruce A; Hyun, Choi; Lee, Woan-Ruah; Sanford, James A; Gallo, Richard L; Ran, Yuping; Chen, Wan-Tzu; Huang, Chun-Jen; Hsieh, Ming-Fa; Huang, Chun-Ming

2017-01-01

Many human skin diseases, such as seborrheic dermatitis, potentially occur due to the over-growth of fungi. It remains a challenge to develop fungicides with a lower risk of generating resistant fungi and non-specifically killing commensal microbes. Our probiotic approaches using a selective fermentation initiator of skin commensal bacteria, fermentation metabolites or their derivatives provide novel therapeutics to rein in the over-growth of fungi. Staphylococcus lugdunensis (S. lugdunensis) bacteria and Candida parapsilosis (C. parapsilosis) fungi coexist in the scalp microbiome. S. lugdunensis interfered with the growth of C. parapsilosis via fermentation. A methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) copolymer functioned as a selective fermentation initiator of S. lugdunensis, selectively triggering the S. lugdunensis fermentation to produce acetic and isovaleric acids. The acetic acid and its pro-drug diethyleneglycol diacetate (Ac-DEG-Ac) effectively suppressed the growth of C. parapsilosis in vitro and impeded the fungal expansion in the human dandruff. We demonstrate for the first time that S. lugdunensis is a skin probiotic bacterium that can exploit mPEG-PCL to yield fungicidal short-chain fatty acids (SCFAs). The concept of bacterial fermentation as a part of skin immunity to re-balance the dysbiotic microbiome warrants a novel avenue for studying the probiotic function of the skin microbiome in promoting health. PMID:28111598

An Injectable Hydrogel Prepared Using a PEG/Vitamin E Copolymer Facilitating Aqueous-Driven Gelation.

PubMed

Zhang, Jianfeng; Muirhead, Ben; Dodd, Megan; Liu, Lina; Xu, Fei; Mangiacotte, Nicole; Hoare, Todd; Sheardown, Heather

2016-11-14

Hydrogels have been widely explored for biomedical applications, with injectable hydrogels being of particular interest for their ability to precisely deliver drugs and cells to targets. Although these hydrogels have demonstrated satisfactory properties in many cases, challenges still remain for commercialization. In this paper, we describe a simple injectable hydrogel based on poly(ethylene glycol) (PEG) and a vitamin E (Ve) methacrylate copolymer prepared via simple free radical polymerization and delivered in a solution of low molecular weight PEG and Ve as the solvent instead of water. The hydrogel formed immediately in an aqueous environment with a controllable gelation time. The driving force for gelation is attributed to the self-assembly of hydrophobic Ve residues upon exposure to water to form a physically cross-linked polymer network via polymer chain rearrangement and subsequent phase separation, a spontaneous process with water uptake. The hydrogels can be customized to give the desired water content, mechanical strength, and drug release kinetics simply by formulating the PEGMA-co-Ve polymer with an appropriate solvent mixture or by varying the molecular weight of the polymer. The hydrogels exhibited no significant cytotoxicity in vitro using fibroblasts and good tissue compatibility in the eye and when injected subcutaneously. These polymers thus have the potential to be used in a variety of applications where injection of a drug or cell containing depot would be desirable.

Rheo-optical near-infrared (NIR) spectroscopy study of partially miscible polymer blend of polymethyl methacrylate (PMMA) and polyethylene glycol (PEG)

NASA Astrophysics Data System (ADS)

Shinzawa, Hideyuki; Mizukado, Junji

2018-03-01

Tensile deformations of a partially miscible blend of polymethyl methacrylate (PMMA) and polyethylene glycol (PEG) is studied by a rheo-optical characterization near-infrared (NIR) technique to probe deformation behavior during tensile deformation. Sets of NIR spectra of the polymer samples were collected by using an acousto-optic tunable filter (AOTF) NIR spectrometer coupled with a tensile testing machine as an excitation device. While deformations of the samples were readily captured as strain-dependent NIR spectra, the entire feature of the spectra was overwhelmed with the baseline fluctuation induced by the decrease in the sample thickness and subsequent change in the light scattering. Several pretreatment techniques, including multiplicative scatter collection (MSC) and null-space projection, are subjected to the NIR spectra prior to the determination of the sequential order of the spectral intensity changes by two-dimensional (2D) correlation analysis. The comparison of the MSC and null-space projection provided an interesting insight into the system, especially deformation-induced variation of light scattering observed during the tensile testing of the polymer sample. In addition, the sequential order determined with the 2D correlation spectra revealed that orientation of a specific part of PMMA chain occurs before that of the others because of the interaction between Cdbnd O group of PMMA and terminal sbnd OH group of PEG.

Production of mono- and di-carboxylated polyethylene glycols as a factor obstacle to the successful ozonation-assisted biodegradation of ethoxylated compounds.

PubMed

Nakai, Satoshi; Okuda, Tetsuji; Nishijima, Wataru; Okada, Mitsumasa

2015-10-01

Ozonation is believed to improve the biodegradability of organic compounds. In the present study, degradation of nonylphenol ethoxylates (NPEOs) was monitored in hybrid treatment systems consisting of ozonation and microbial degradation processes. We found that ozonation of NPEOs decreased, rather than increased, the biodegradability under certain conditions. The timing of ozonation was a definitive factor in determining whether ozonation increased or decreased the biodegradation rates of NPEOs. Initial ozonation of NPEOs prior to biodegradation reduced the rate of dissolved organic carbon (DOC) removal during the subsequent 14 d of biodegradation, whereas intermediate ozonation at the 9th day of biodegradation improved subsequent DOC removal during 14 d of NPEO biodegradation. Furthermore, reduction of DOC removal was also observed, when initial ozonation prior to biodegradation was subjected to cetyl alcohol ethoxylates. The production of less biodegradable intermediates, such as mono- and dicarboxylated polyethylene glycols (MCPEGs and DCPEGs), was responsible for the negative effect of ozonation on biodegradability of NPEOs. DCPEGs and MCPEGs were produced by biodegradation of polyethylene glycols (PEGs) that were ozonolysis products of the NPEOs, and the biodegradability of DCPEGs and MCPEGs was less than that of the precursor PEGs. The results indicate that, if the target chemicals contain ethoxy chains, production of PEGs may be one of the important factors when ozonation is considered. Copyright © 2015 Elsevier Ltd. All rights reserved.

Elucidation of the electronic states in polyethylene glycol by attenuated Total reflectance spectroscopy in the far-ultraviolet region

NASA Astrophysics Data System (ADS)

Ueno, Nami; Wakabayashi, Tomonari; Morisawa, Yusuke

2018-05-01

We measured the attenuated total reflectance-far ultraviolet (ATR-FUV) spectra of poly(ethylene glycol) (PEG; average molecular weights of 200, 300, and 400) and related materials in the liquid state in the 145-200-nm wavelength region. For appropriately assigning the absorption bands, we also performed theoretical simulation of the unit-number dependent electronic spectra. The FUV spectra of PEGs contain three bands, which are assigned to the transitions between n(CH2OCH2)-3s Rydberg state (176 nm), n(CH2OCH2)-3p Rydberg state (163 nm), and n(OH)-3p Rydberg state (153 nm). Since the contribution of n(OH) decreases compared to n(CH2OCH2) with increase in the number of units, the ratios of the molar absorption coefficients, ε, at 153 nm relative to 163 nm, decrease. On the other hand, the ratio of ε at 176 nm to that at 163 nm increases with increase in the number of units, because of the difference in the number of unoccupied orbitals in the transitions. The calculated results suggest that n orbitals form two electronic bands. In the upper band, the electrons expand over the ether chain, whereas in the lower band, the electrons are localized in the terminal OH in the PEGs.

Thermoresponsive Supramolecular Chemotherapy by "V"-Shaped Armed β-Cyclodextrin Star Polymer to Overcome Drug Resistance.

PubMed

Fan, Xiaoshan; Cheng, Hongwei; Wang, Xiaoyuan; Ye, Enyi; Loh, Xian Jun; Wu, Yun-Long; Li, Zibiao

2018-04-01

Pump mediated drug efflux is the key reason to result in the failure of chemotherapy. Herein, a novel star polymer β-CD-v-(PEG-β-PNIPAAm) 7 consisting of a β-CD core, grafted with thermo-responsive poly(N-isopropylacrylamide) (PNIPAAm) and biocompatible poly(ethylene glycol) (PEG) in the multiple "V"-shaped arms is designed and further fabricated into supramolecular nanocarriers for drug resistant cancer therapy. The star polymer could encapsulate chemotherapeutics between β-cyclodextrin and anti-cancer drug via inclusion complex (IC). Furthermore, the temperature induced chain association of PNIPAAm segments facilitated the IC to form supramolecular nanoparticles at 37 °C, whereas the presence of PEG impart great stability to the self-assemblies. When incubated with MDR-1 membrane pump regulated drug resistant tumor cells, much higher and faster cellular uptake of the supramolecular nanoparticles were detected, and the enhanced intracellular retention of drugs could lead to significant inhibition of cell growth. Further in vivo evaluation showed high therapeutic efficacy in suppressing drug resistant tumor growth without a significant impact on the normal functions of main organs. This work signifies thermo-responsive supramolecular chemotherapy is promising in combating pump mediated drug resistance in both in vitro and in vivo models, which may be encouraging for the advanced drug delivery platform design to overcome drug resistant cancer. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Twist-writhe partitioning in a coarse-grained DNA minicircle model

NASA Astrophysics Data System (ADS)

Sayar, Mehmet; Avşaroǧlu, Barış; Kabakçıoǧlu, Alkan

2010-04-01

Here we present a systematic study of supercoil formation in DNA minicircles under varying linking number by using molecular-dynamics simulations of a two-bead coarse-grained model. Our model is designed with the purpose of simulating long chains without sacrificing the characteristic structural properties of the DNA molecule, such as its helicity, backbone directionality, and the presence of major and minor grooves. The model parameters are extracted directly from full-atomistic simulations of DNA oligomers via Boltzmann inversion; therefore, our results can be interpreted as an extrapolation of those simulations to presently inaccessible chain lengths and simulation times. Using this model, we measure the twist/writhe partitioning in DNA minicircles, in particular its dependence on the chain length and excess linking number. We observe an asymmetric supercoiling transition consistent with experiments. Our results suggest that the fraction of the linking number absorbed as twist and writhe is nontrivially dependent on chain length and excess linking number. Beyond the supercoiling transition, chains of the order of one persistence length carry equal amounts of twist and writhe. For longer chains, an increasing fraction of the linking number is absorbed by the writhe.

Intensified fractionation of brewery yeast waste for the recovery of invertase using aqueous two-phase systems.

PubMed

De León-González, Grecia; González-Valdez, José; Mayolo-Deloisa, Karla; Rito-Palomares, Marco

2016-11-01

The potential recovery of high-value products from brewery yeast waste confers value to this industrial residue. Aqueous two-phase systems (ATPS) have demonstrated to be an attractive alternative for the primary recovery of biological products and are therefore suitable for the recovery of invertase from this residue. Sixteen different polyethylene glycol (PEG)-potassium phosphate ATPS were tested to evaluate the effects of PEG molecular weight (MW) and tie-line length (TLL) upon the partition behavior of invertase. Concentrations of crude extract from brewery yeast waste were then varied in the systems that presented the best behaviors to intensify the potential recovery of the enzyme. Results show that the use of a PEG MW 400 g mol -1 system with a TLL of 45.0% (w/w) resulted in an invertase bottom phase recovery with a purification factor of 29.5 and a recovery yield of up to 66.2% after scaling the system to a total weight of 15.0 g. This represents 15.1 mg of invertase per mL of processed bottom phase. With these results, a single-stage ATPS process for the recovery of invertase is proposed. © 2015 International Union of Biochemistry and Molecular Biology, Inc.

Alginate oligosaccharides enhanced Triticum aestivum L. tolerance to drought stress.

PubMed

Liu, Hang; Zhang, Yun-Hong; Yin, Heng; Wang, Wen-Xia; Zhao, Xiao-Ming; Du, Yu-Guang

2013-01-01

Alginate oligosaccharides (AOS) prepared from degradation of alginate is a potent plant elicitor. Hydroponic experiments were carried out to investigate the mechanism of AOS on improving Triticum aestivum L. resistant ability to drought stress. Drought model was simulated by exposing the roots of wheat to polyethylene glycol-6000 (PEG-6000) solution (150 g L(-1)) for 4 days and the growth of wheat treated with PEG was significantly decreased. However, after AOS application, seedling and root length, fresh weight and relative water content of wheat were increased by 18%, 26%, 43% and 33% under dehydration status compared with that of PEG group, respectively. Moreover, the antioxidative enzymes activities were obviously enhanced and malondialdehyde (MDA) content was reduced by 37.9% in samples treated by AOS. Additionally, the drought resistant related genes involved in ABA signal pathway, such as late embryogenesis abundant protein 1 gene (LEA1), psbA gene, Sucrose non-fermenting 1-related protein kinase 2 gene (SnRK2) and Pyrroline-5-Carboxylate Synthetase gene (P5CS) were up-regulated by AOS. Our results suggested that AOS might regulate ABA-dependent signal pathway to enhance drought stress resistance of wheat during growth period. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Elongated phytoglycogen chain length in transgenic rice endosperm expressing active starch synthase IIa affects the altered solubility and crystallinity of the storage α-glucan

PubMed Central

Fujita, Naoko; Toyosawa, Yoshiko; Utsumi, Yoshinori

2012-01-01

The relationship between the solubility, crystallinity, and length of the unit chains of plant storage α-glucan was investigated by manipulating the chain length of α-glucans accumulated in a rice mutant. Transgenic lines were produced by introducing a cDNA for starch synthase IIa (SSIIa) from an indica cultivar (SSIIa I, coding for active SSIIa) into an isoamylase1 (ISA1)-deficient mutant (isa1) that was derived from a japonica cultivar (bearing inactive SSIIa proteins). The water-soluble fraction accounted for >95% of the total α-glucan in the isa1 mutant, whereas it was only 35–70% in the transgenic SSIIa I /isa1 lines. Thus, the α-glucans from the SSIIa I /isa1 lines were fractionated into soluble and insoluble fractions prior to the following characterizations. X-ray diffraction analysis revealed a weak B-type crystallinity for the α-glucans of the insoluble fraction, while no crystallinity was confirmed for α-glucans in isa1. Concerning the degree of polymerization (DP) ≤30, the chain lengths of these α-glucans differed significantly in the order of SSIIa I /isa1 insoluble > SSIIa I /isa1 soluble > α-glucans in isa1. The amount of long chains with DP ≥33 was higher in the insoluble fraction α-glucans than in the other two α-glucans. No difference was observed in the chain length distributions of the β-amylase limit dextrins among these α-glucans. These results suggest that in the SSIIa I /isa1 transgenic lines, the unit chains of α-glucans were elongated by SSIIaI, whereas the expression of SSIIaI did not affect the branch positions. Thus, the observed insolubility and crystallinity of the insoluble fraction can be attributed to the elongated length of the outer chains due to SSIIaI. PMID:23048127

The electrostatic persistence length of polymers beyond the OSF limit.

PubMed

Everaers, R; Milchev, A; Yamakov, V

2002-05-01

We use large-scale Monte Carlo simulations to test scaling theories for the electrostatic persistence length l(e) of isolated, uniformly charged polymers with Debye-Hückel intrachain interactions in the limit where the screening length kappa(-1) exceeds the intrinsic persistence length of the chains. Our simulations cover a significantly larger part of the parameter space than previous studies. We observe no significant deviations from the prediction l(e) proportional to kappa(-2) by Khokhlov and Khachaturian which is based on applying the Odijk-Skolnick-Fixman theories of electrostatic bending rigidity and electrostatically excluded volume to the stretched de Gennes-Pincus-Velasco-Brochard polyelectrolyte blob chain. A linear or sublinear dependence of the persistence length on the screening length can be ruled out. We show that previous results pointing into this direction are due to a combination of excluded-volume and finite chain length effects. The paper emphasizes the role of scaling arguments in the development of useful representations for experimental and simulation data.

Anti-proliferative effects of O-acyl-low-molecular-weight heparin derivatives on bovine pulmonary artery smooth muscle cells.

PubMed

Garg, Hari G; Mrabat, Hicham; Yu, Lunyin; Hales, Charles A; Li, Boyangzi; Moore, Casey N; Zhang, Fuming; Linhardt, Robert J

2011-08-01

Heparin (HP) inhibits the growth of several cell types in vitro including bovine pulmonary artery (BPA) smooth muscle cells (SMCs). In initial studies we discovered that an O-hexanoylated low-molecular-weight (LMW) HP derivative having acyl groups with 6-carbon chain length was more potent inhibitor of BPA-SMCs than the starting HP. We prepared several O-acylated LMWHP derivatives having 4-, 6-, 8-, 10-, 12-, and 18- carbon acyl chain lengths to determine the optimal acyl chain length for maximum anti-proliferative properties of BPA-SMCs. The starting LMWHP was prepared from unfractionated HP by sodium periodate treatment followed by sodium borohydride reduction. The tri-n-butylammonium salt of this LMWHP was O-acylated with butanoic, hexanoic, octanoic, decanoic, dodecanoic, and stearyl anhydrides separately to give respective O-acylated LMWHP derivatives. Gradient polyacrylamide gel electrophoresis (PAGE) was used to examine the average molecular weights of those O-acylated LMWHP derivatives. NMR analysis indicated the presence of one O-acyl group per disaccharide residue. Measurement of the inhibition of BPA-SMCS as a function of O-acyl chain length shows two optima, at a carbon chain length of 6 (O-hexanoylated LMWHP) and at a carbon chain length 12-18 (O-dodecanoyl and O-stearyl LMWHPs). A solution competition SPR study was performed to test the ability of different O-acylated LMWHP derivatives to inhibit fibroblast growth factor (FGF) 1 and FGF2 binding to surface-immobilized heparin. All the LMWHP derivatives bound to FGF1 and FGF2 but each exhibited slightly different binding affinity.

How ionic species structure influences phase structure and transitions from protic ionic liquids to liquid crystals to crystals.

PubMed

Greaves, Tamar L; Broomhall, Hayden; Weerawardena, Asoka; Osborne, Dale A; Canonge, Bastien A; Drummond, Calum J

2017-12-14

The phase behaviour of n-alkylammonium (C6 to C16) nitrates and formates has been characterised using synchrotron small angle and wide angle X-ray scattering (SAXS/WAXS), differential scanning calorimetry (DSC), cross polarised optical microscopy (CPOM) and Fourier transform infrared spectroscopy (FTIR). The protic salts may exist as crystalline, liquid crystalline or ionic liquid materials depending on the alkyl chain length and temperature. n-Alkylammonium nitrates with n ≥ 6 form thermotropic liquid crystalline (LC) lamellar phases, whereas n ≥ 8 was required for the formate series to form this LC phase. The protic ionic liquid phase showed an intermediate length scale nanostructure resulting from the segregation of the polar and nonpolar components of the ionic liquid. This segregation was enhanced for longer n-alkyl chains, with a corresponding increase in the correlation length scale. The crystalline and liquid crystalline phases were both lamellar. Phase transition temperatures, lamellar d-spacings, and liquid correlation lengths for the n-alkylammonium nitrates and formates were compared with those for n-alkylammonium chlorides and n-alkylamines. Plateau regions in the liquid crystalline to liquid phase transition temperatures as a function of n for the n-alkylammonium nitrates and formates are consistent with hydrogen-bonding and cation-anion interactions between the ionic species dominating alkyl chain-chain van der Waals interactions, with the exception of the mid chained hexyl- and heptylammonium formates. The d-spacings of the lamellar phases for both the n-alkylammonium nitrates and formates were consistent with an increase in chain-chain layer interdigitation within the bilayer-based lamellae with increasing alkyl chain length, and they were comparable to the n-alkylammonium chlorides.

Effect of charged amino acid side chain length on lateral cross-strand interactions between carboxylate- and guanidinium-containing residues in a β-hairpin.

PubMed

Kuo, Hsiou-Ting; Liu, Shing-Lung; Chiu, Wen-Chieh; Fang, Chun-Jen; Chang, Hsien-Chen; Wang, Wei-Ren; Yang, Po-An; Li, Jhe-Hao; Huang, Shing-Jong; Huang, Shou-Ling; Cheng, Richard P

2015-05-01

β-Sheet is one of the major protein secondary structures. Oppositely charged residues are frequently observed across neighboring strands in antiparallel sheets, suggesting the importance of cross-strand ion pairing interactions. The charged amino acids Asp, Glu, Arg, and Lys have different numbers of hydrophobic methylenes linking the charged functionality to the backbone. To investigate the effect of side chain length of guanidinium- and carboxylate-containing residues on lateral cross-strand ion pairing interactions at non-hydrogen-bonded positions, β-hairpin peptides containing Zbb-Agx (Zbb = Asp, Glu, Aad in increasing length; Agx = Agh, Arg, Agb, Agp in decreasing length) sequence patterns were studied by NMR methods. The fraction folded population and folding energy were derived from the chemical shift deviation data. Peptides with high fraction folded populations involved charged residue side chain lengths that supported high strand propensity. Double mutant cycle analysis was used to determine the interaction energy for the potential lateral ion pairs. Minimal interaction was observed between residues with short side chains, most likely due to the diffused positive charge on the guanidinium group, which weakened cross-strand electrostatic interactions with the carboxylate side chain. Only the Aad-Arg/Agh interactions with long side chains clearly exhibited stabilizing energetics, possibly relying on hydrophobics. A survey of a non-redundant protein structure database revealed that the statistical sheet pair propensity followed the trend Asp-Arg < Glu-Arg, implying the need for matching long side chains. This suggested the need for long side chains on both guanidinium-bearing and carboxylate-bearing residues to stabilize the β-hairpin motif.

Chain Assembly and Disassembly Processes Differently Affect the Conformational Space of Ubiquitin Chains.

PubMed

Kniss, Andreas; Schuetz, Denise; Kazemi, Sina; Pluska, Lukas; Spindler, Philipp E; Rogov, Vladimir V; Husnjak, Koraljka; Dikic, Ivan; Güntert, Peter; Sommer, Thomas; Prisner, Thomas F; Dötsch, Volker

2018-02-06

Ubiquitination is the most versatile posttranslational modification. The information is encoded by linkage type as well as chain length, which are translated by ubiquitin binding domains into specific signaling events. Chain topology determines the conformational space of a ubiquitin chain and adds an additional regulatory layer to this ubiquitin code. In particular, processes that modify chain length will be affected by chain conformations as they require access to the elongation or cleavage sites. We investigated conformational distributions in the context of chain elongation and disassembly using pulsed electron-electron double resonance spectroscopy in combination with molecular modeling. Analysis of the conformational space of diubiquitin revealed conformational selection or remodeling as mechanisms for chain recognition during elongation or hydrolysis, respectively. Chain elongation to tetraubiquitin increases the sampled conformational space, suggesting that a high intrinsic flexibility of K48-linked chains may contribute to efficient proteasomal degradation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Critical temperatures and a critical chain length in saturated diacylphosphatidylcholines: calorimetric, ultrasonic and Monte Carlo simulation study of chain-melting/ordering in aqueous lipid dispersions.

PubMed

Kharakoz, Dmitry P; Panchelyuga, Maria S; Tiktopulo, Elizaveta I; Shlyapnikova, Elena A

2007-12-01

Chain-ordering/melting transition in a series of saturated diacylphosphatidylcholines (PCs) in aqueous dispersions have been studied experimentally (calorimetric and ultrasonic techniques) and theoretically (an Ising-like lattice model). The shape of the calorimetric curves was compared with the theoretical data and interpreted in terms of the lateral interactions and critical temperatures determined for each lipid studied. A critical chain length has been found (between 16 and 17 C-atoms per chain) which subdivides PCs into two classes with different phase behavior. In shorter lipids, the transition takes place above their critical temperatures meaning that this is an intrinsically continuous transition. In longer lipids, the transition occurs below the critical temperatures of the lipids, meaning that the transition is intrinsically discontinuous (first-order). This conclusion was supported independently by the ultrasonic relaxation sensitive to density fluctuations. Interestingly, it is this length that is the most abundant among the saturated chains in biological membranes.

Molecular structure of quinoa starch.

PubMed

Li, Guantian; Zhu, Fan

2017-02-20

Quinoa starch has very small granules with unique properties. However, the molecular structure of quinoa starch remains largely unknown. In this study, composition and amylopectin molecular structure of 9 quinoa starch samples were characterised by chromatographic techniques. In particular, the amylopectin internal molecular structure, represented by φ, β-limit dextrins (LDs), was explored. Great variations in the composition and molecular structures were recorded among samples. Compared with other amylopectins, quinoa amylopectin showed a high ratio of short chain to long chains (mean:14.6) and a high percentage of fingerprint A-chains (A fp ) (mean:10.4%). The average chain length, external chain length, and internal chain length of quinoa amylopectin were 16.6, 10.6, and 5.00 glucosyl residues, respectively. Pearson correlation and principal component analysis revealed some inherent correlations among structural parameters and a similarity of different samples. Overall, quinoa amylopectins are structurally similar to that from starches with A-type polymorph such as oat and amaranth starches. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chain-Length-Dependent Exciton Dynamics in Linear Oligothiophenes Probed Using Ensemble and Single-Molecule Spectroscopy.

PubMed

Kim, Tae-Woo; Kim, Woojae; Park, Kyu Hyung; Kim, Pyosang; Cho, Jae-Won; Shimizu, Hideyuki; Iyoda, Masahiko; Kim, Dongho

2016-02-04

Exciton dynamics in π-conjugated molecular systems is highly susceptible to conformational disorder. Using time-resolved and single-molecule spectroscopic techniques, the effect of chain length on the exciton dynamics in a series of linear oligothiophenes, for which the conformational disorder increased with increasing chain length, was investigated. As a result, extraordinary features of the exciton dynamics in longer-chain oligothiophene were revealed. Ultrafast fluorescence depolarization processes were observed due to exciton self-trapping in longer and bent chains. Increase in exciton delocalization during dynamic planarization processes was also observed in the linear oligothiophenes via time-resolved fluorescence spectra but was restricted in L-10T because of its considerable conformational disorder. Exciton delocalization was also unexpectedly observed in a bent chain using single-molecule fluorescence spectroscopy. Such delocalization modulates the fluorescence spectral shape by attenuating the 0-0 peak intensity. Collectively, these results provide significant insights into the exciton dynamics in conjugated polymers.

Acute hepatitis C: a 24-week course of pegylated interferon α-2b versus a 12-week course of pegylated interferon α-2b alone or with ribavirin.

PubMed

Santantonio, Teresa; Fasano, Massimo; Sagnelli, Evangelista; Tundo, Paolo; Babudieri, Sergio; Fabris, Paolo; Toti, Mario; Di Perri, Giovanni; Marino, Nicoletta; Pizzigallo, Eligio; Angarano, Gioacchino

2014-06-01

Therapy of acute hepatitis C (AHC) has not yet been standardized and several issues are still unresolved. This open, randomized, multicenter trial aimed to assess the efficacy and safety of a 24-week course of pegylated IFN (Peg-IFN) alpha-2b versus a 12-week course of Peg-IFN alpha-2b alone or with ribavirin (RBV) in AHC patients. One hundred and thirty HCV acutely infected patients who did not spontaneously resolve by week 12 after onset were consecutively enrolled and randomized to receive Peg-IFN alpha-2b monotherapy (1.5 μg/kg/week) for 24 or 12 weeks (arm 1, n = 44 and arm 2, n = 43, respectively) or in combination with RBV (10.6 mg/kg/day) for 12 weeks (arm 3, n = 43). The primary endpoint was undetectable HCV RNA at 6-month posttreatment follow-up (sustained virological response; SVR). All patients were followed for 48 weeks after therapy cessation. HCV RNA levels were determined by real-time polymerase chain reaction (limit of detection: 15 IU/mL) at the central laboratory at baseline, week 4, end of treatment, and 6 and 12 months posttreatment. Using an intent-to-treat analysis, overall SVR rate was 71.5%. In particular, an SVR was achieved in 31 of 44 (70.5%), 31 of 43 (72.1%), and 31 of 43 (72.1%) patients in arms 1, 2, and 3, respectively (P = 0.898). Sixteen patients (12.3%) prematurely discontinued therapy or were lost to follow-up; thus, sustained response rates with per-protocol analysis were 81.6%, 81.6%, and 81.6% for patients in arms 1, 2, and 3 respectively. With multivariate analysis, virologic response at week 4 of treatment was an independent predictor of SVR. Peg-IFN alpha-2b was well tolerated. Peg-IFN alpha-2b induces a high SVR in chronically evolving AHC patients. Response rates were not influenced by combination therapy or treatment duration. © 2014 by the American Association for the Study of Liver Diseases.

Targeting hepatic cancer cells with pegylated dendrimers displaying N-acetylgalactosamine and SP94 peptide ligands.

PubMed

Medina, Scott H; Tiruchinapally, Gopinath; Chevliakov, Maxim V; Durmaz, Yasemin Yuksel; Stender, Rachell N; Ensminger, William D; Shewach, Donna S; Elsayed, Mohamed E H

2013-10-01

Poly(amidoamine) (PAMAM) dendrimers are branched water-soluble polymers defined by consecutive generation numbers (Gn) indicating a parallel increase in size, molecular weight, and number of surface groups available for conjugation of bioactive agents. In this article, we compare the biodistribution of N-acetylgalactosamine (NAcGal)-targeted [(14) C]1 -G5-(NH2 )5 -(Ac)108 -(NAcGal)14 particles to non-targeted [(14) C]1 -G5-(NH2 )127 and PEGylated [(14) C]1 -G5-(NH2 )44 -(Ac)73 -(PEG)10 particles in a mouse hepatic cancer model. Results show that both NAcGal-targeted and non-targeted particles are rapidly cleared from the systemic circulation with high distribution to the liver. However, NAcGal-targeted particles exhibited 2.5-fold higher accumulation in tumor tissue compared to non-targeted ones. In comparison, PEGylated particles showed a 16-fold increase in plasma residence time and a 5-fold reduction in liver accumulation. These results motivated us to engineer new PEGylated G5 particles with PEG chains anchored to the G5 surface via acid-labile cis-aconityl linkages where the free PEG tips are functionalized with NAcGal or SP94 peptide to investigate their potential as targeting ligands for hepatic cancer cells as a function of sugar conformation (α versus β), ligand concentration (100-4000 nM), and incubation time (2 and 24 hours) compared to fluorescently (Fl)-labeled and non-targeted G5-(Fl)6 -(NH2 )122 and G5-(Fl)6 -(Ac)107 -(cPEG)15 particles. Results show G5-(Fl)6 -(Ac)107 -(cPEG[NAcGalβ ])14 particles achieve faster uptake and higher intracellular concentrations in HepG2 cancer cells compared to other G5 particles while escaping the non-specific adsorption of serum protein and phagocytosis by Kupffer cells, which make these particles the ideal carrier for selective drug delivery into hepatic cancer cells. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cloud point phenomena for POE-type nonionic surfactants in a model room temperature ionic liquid.

PubMed

Inoue, Tohru; Misono, Takeshi

2008-10-15

The cloud point phenomenon has been investigated for the solutions of polyoxyethylene (POE)-type nonionic surfactants (C(12)E(5), C(12)E(6), C(12)E(7), C(10)E(6), and C(14)E(6)) in 1-butyl-3-methylimidazolium tetrafluoroborate (bmimBF(4)), a typical room temperature ionic liquid (RTIL). The cloud point, T(c), increases with the elongation of the POE chain, while decreases with the increase in the hydrocarbon chain length. This demonstrates that the solvophilicity/solvophobicity of the surfactants in RTIL comes from POE chain/hydrocarbon chain. When compared with an aqueous system, the chain length dependence of T(c) is larger for the RTIL system regarding both POE and hydrocarbon chains; in particular, hydrocarbon chain length affects T(c) much more strongly in the RTIL system than in equivalent aqueous systems. In a similar fashion to the much-studied aqueous systems, the micellar growth is also observed in this RTIL solvent as the temperature approaches T(c). The cloud point curves have been analyzed using a Flory-Huggins-type model based on phase separation in polymer solutions.

A kinetic theory description of the viscosity of dense fluids consisting of chain molecules.

PubMed

de Wijn, Astrid S; Vesovic, Velisa; Jackson, George; Trusler, J P Martin

2008-05-28

An expression for the viscosity of a dense fluid is presented that includes the effect of molecular shape. The molecules of the fluid are approximated by chains of equal-sized, tangentially jointed, rigid spheres. It is assumed that the collision dynamics in such a fluid can be approximated by instantaneous collisions between two rigid spheres belonging to different chains. The approach is thus analogous to that of Enskog for a fluid consisting of rigid spheres. The description is developed in terms of two molecular parameters, the diameter sigma of the spherical segment and the chain length (number of segments) m. It is demonstrated that an analysis of viscosity data of a particular pure fluid alone cannot be used to obtain independently effective values of both sigma and m. Nevertheless, the chain lengths of n-alkanes are determined by assuming that the diameter of each rigid sphere making up the chain can be represented by the diameter of a methane molecule. The effective chain lengths of n-alkanes are found to increase linearly with the number C of carbon atoms present. The dependence can be approximated by a simple relationship m=1+(C-1)3. The same relationship was reported within the context of a statistical associating fluid theory equation of state treatment of the fluid, indicating that both the equilibrium thermodynamic properties and viscosity yield the same value for the chain lengths of n-alkanes.

ε-Poly-L-lysine peptide chain length regulated by the linkers connecting the transmembrane domains of ε-Poly-L-lysine synthetase.

PubMed

Hamano, Yoshimitsu; Kito, Naoko; Kita, Akihiro; Imokawa, Yuuki; Yamanaka, Kazuya; Maruyama, Chitose; Katano, Hajime

2014-08-01

ε-Poly-l-lysine (ε-PL), consisting of 25 to 35 l-lysine residues with linkages between the α-carboxyl groups and ε-amino groups, is produced by Streptomyces albulus NBRC14147. ε-PL synthetase (Pls) is a membrane protein with six transmembrane domains (TM1 to TM6) as well as both an adenylation domain and a thiolation domain, characteristic of the nonribosomal peptide synthetases. Pls directly generates ε-PL chain length diversity (25- to 35-mer), but the processes that control the chain length of ε-PL during the polymerization reaction are still not fully understood. Here, we report on the identification of Pls amino acid residues involved in the regulation of the ε-PL chain length. From approximately 12,000 variants generated by random mutagenesis, we found 8 Pls variants that produced shorter chains of ε-PL. These variants have one or more mutations in two linker regions connecting the TM1 and TM2 domains and the TM3 and TM4 domains. In the Pls catalytic mechanism, the growing chain of ε-PL is not tethered to the enzyme, implying that the enzyme must hold the growing chain until the polymerization reaction is complete. Our findings reveal that the linker regions are important contributors to grasp the growing chain of ε-PL. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Polyphosphate kinase: demonstration that short chain polyphosphate serves as a primer for the enzymatic synthesis of polyphosphate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robinson, N.A.; Wood, H.G.

1986-05-01

Polyphosphate (poly(P)) kinase, isolated from Propionibacterium shermanii, catalyzes the following reaction: poly(P/sub n/) + ATPin equilibriumpoly(P/sub n+1/) + ADP. The authors have purified this enzyme to 90% homogeneity and have shown it to be composed of 2-3 identical subunits of M/sub r/ 80,000. Investigation of the reaction mechanism by product analysis has revealed that the elongation phase is processive whereby successive elongation occurs without release of intermediate sizes until very long chains are formed. The initiation phase of synthesis has been investigated using (/sup 32/P) poly(P) primer of chain length 11-60. It is incorporated into long chain poly(P) and themore » /sup 32/P has been shown, by use of poly(P) glucokinase, to be localized at the end of the molecule. Calculation of average chain length based upon the incorporation of /sup 32/P, however, yields a value approx.3 fold higher than the value calculated by another method using poly(P) glucokinase. This result indicates that initiation of poly(P) synthesis occurs by at least one other route which does not involve short chain poly(P) primers. The effect of temperature and concentration of poly(P) primer upon the average chain length of poly(P) synthesized was also investigated. A general trend was observed in which the chain length of the synthesized poly(P) decreased as either temperature or concentration or primer was increased.« less

Generalized theory of semiflexible polymers.

PubMed

Wiggins, Paul A; Nelson, Philip C

2006-03-01

DNA bending on length scales shorter than a persistence length plays an integral role in the translation of genetic information from DNA to cellular function. Quantitative experimental studies of these biological systems have led to a renewed interest in the polymer mechanics relevant for describing the conformational free energy of DNA bending induced by protein-DNA complexes. Recent experimental results from DNA cyclization studies have cast doubt on the applicability of the canonical semiflexible polymer theory, the wormlike chain (WLC) model, to DNA bending on biologically relevant length scales. This paper develops a theory of the chain statistics of a class of generalized semiflexible polymer models. Our focus is on the theoretical development of these models and the calculation of experimental observables. To illustrate our methods, we focus on a specific, illustrative model of DNA bending. We show that the WLC model generically describes the long-length-scale chain statistics of semiflexible polymers, as predicted by renormalization group arguments. In particular, we show that either the WLC or our present model adequately describes force-extension, solution scattering, and long-contour-length cyclization experiments, regardless of the details of DNA bend elasticity. In contrast, experiments sensitive to short-length-scale chain behavior can in principle reveal dramatic departures from the linear elastic behavior assumed in the WLC model. We demonstrate this explicitly by showing that our toy model can reproduce the anomalously large short-contour-length cyclization factors recently measured by Cloutier and Widom. Finally, we discuss the applicability of these models to DNA chain statistics in the context of future experiments.

RAFT-synthesized Graft Copolymers that Enhance pH-dependent Membrane Destabilization and Protein Circulation Times

PubMed Central

Crownover, Emily; Duvall, Craig L.; Convertine, Anthony; Hoffman, Allan S.; Stayton, Patrick S.

2012-01-01

Here we describe a new graft copolymer architecture of poly(propylacrylic acid) (polyPAA) that displays potent pH-dependent, membrane-destabilizing activity and in addition is shown to enhance protein blood circulation kinetics. PolyPAA containing a single telechelic alkyne functionality was prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization with an alkyne-functional chain transfer agent (CTA) and coupled to RAFT polymerized poly(azidopropyl methacrylate) (polyAPMA) through azide-alkyne [3+2] Huisgen cycloaddition. The graft copolymers become membrane destabilizing at endosomal pH values and are active at significantly lower concentrations than the linear polyPAA. A biotin terminated polyPAA graft copolymer was prepared by grafting PAA onto polyAPMA polymerized with a biotin functional RAFT CTA. The blood circulation time and biodistribution of tritium labeled avidin conjugated to the polyPAA graft copolymer was characterized along with a clinically utilized 40 kDa branched polyethylene glycol (PEG) also possessing biotin functionalization. The linear and graft polyPAA increase the area under the curve (AUC) over avidin alone by 9 and 12 times, respectively. Furthermore, polyPAA graft copolymer conjugates accumulated in tumor tissue significantly more than the linear polyPAA and the branched PEG conjugates. The collective data presented in this report indicate that the polyPAA graft copolymers exhibit robust pH-dependent, membrane-destabilizing activity, low cytotoxicity and significantly enhance blood circulation time and tumor accumulation. PMID:21699931

Functionalized PLA polymers to control loading and/or release properties of drug-loaded nanoparticles.

PubMed

Thauvin, Cédric; Schwarz, Bettina; Delie, Florence; Allémann, Eric

2017-11-15

Advantages associated with the use of polylactic acid (PLA) nano- or microparticles as drug delivery systems have been widely proven in the field of pharmaceutical sciences. These biodegradable and biocompatible carriers have demonstrated different loading and release properties depending on interactions with the cargo, preparation methods, particles size or molecular weight of PLA. In this study, we sought to show the possibility of influencing these properties by modifying the structure of the constituting polymer. Seven non-functionalized or functionalized PLA polymers were specifically designed and synthesized by microwave-assisted ring-opening polymerization of d,l-lactide. They presented short hydrophobic and/or hydrophilic groups thanks to the use of C20 aliphatic chain, mPEG1000, sorbitan esters (Spans ® ) or polysorbates (Tweens ® ), their PEGylated analogues, as initiators. Then, seven types of drug-loaded nanoparticles (NP) were prepared from these polymers and compared in terms of physico-chemical characteristics, drug loading and release profiles. Although the loading properties were not improved with any of the functionalized PLA NP, different release profiles were observed in an aqueous medium at 37 °C and over a period of five days. The presence of PEG moieties in the core of PLA-polysorbates NP induced a faster release while the addition of a single aliphatic chain induced a slower release due to better interactions with the active molecule. Copyright © 2017 Elsevier B.V. All rights reserved.

Use of boron cluster-containing redox nanoparticles with ROS scavenging ability in boron neutron capture therapy to achieve high therapeutic efficiency and low adverse effects.

PubMed

Gao, Zhenyu; Horiguchi, Yukichi; Nakai, Kei; Matsumura, Akira; Suzuki, Minoru; Ono, Koji; Nagasaki, Yukio

2016-10-01

A boron delivery system with high therapeutic efficiency and low adverse effects is crucial for a successful boron neutron capture therapy (BNCT). In this study, we developed boron cluster-containing redox nanoparticles (BNPs) via polyion complex (PIC) formation, using a newly synthesized poly(ethylene glycol)-polyanion (PEG-polyanion, possessing a (10)B-enriched boron cluster as a side chain of one of its segments) and PEG-polycation (possessing a reactive oxygen species (ROS) scavenger as a side chain of one of its segments). The BNPs exhibited high colloidal stability, selective uptake in tumor cells, specific accumulation, and long retention in tumor tissue and ROS scavenging ability. After thermal neutron irradiation, significant suppression of tumor growth was observed in the BNP-treated group, with only 5-ppm (10)B in tumor tissues, whereas at least 20-ppm (10)B is generally required for low molecular weight (LMW) (10)B agents. In addition, increased leukocyte levels were observed in the LMW (10)B agent-treated group after thermal neutron irradiation, and not in BNP-treated group, which might be attributed to its ROS scavenging ability. No visual metastasis of tumor cells to other organs was observed 1 month after irradiation in the BNP-treated group. These results suggest that BNPs are promising for enhancing the BNCT performance. Copyright © 2016 Elsevier Ltd. All rights reserved.

Surface grafting of poly(ethylene glycol) onto poly(acrylamide-co-vinyl amine) cross-linked films under mild conditions.

PubMed

Yamamoto, Y; Sefton, M V

1998-01-01

Poly(ethylene glycol) (PEG) was grafted onto poly(acrylamide-co-vinyl amine) (poly(AM-co-VA)) film using tresylated PEG (TPEG) at 37 degrees C in aqueous buffers (pH 7.4) with a view to surface-modifying microencapsulated mammalian cells. Poly(AM-co-VA) film was synthesized by Hofmann degradation of a cross-linked poly(acrylamide) film. Conversion to vinyl amine on the surface of the film was approximately 50%, but bulk conversion was not observed; surface specificity was thought to be the result of cleavage of aminated polymer chains at the surface due to chain scission. Reaction between primary amine and TPEG gave a graft yield of 2 mol% (based on XPS) with respect to available surface amine groups, equivalent to 54 mol% ethylene oxide based on monomer units. Physical adsorption of non-activated polymer was done under identical conditions as a control and the difference in oxygen content was significant compared to TPEG. The type of buffer agent and buffer concentration did not influence graft yields. This graft reaction, which was completed in as little as 2 h was considered to be mild enough to be used for a surface modification of microcapsules containing cells without affecting their viability. Such a surface modification technique may prove to be a useful means of enhancing the biocompatibility of microcapsules (or any tissue engineering construct) even after cell encapsulation or seeding.

Binding of cationic pentapeptides with modified side chain lengths to negatively charged lipid membranes: Complex interplay of electrostatic and hydrophobic interactions.

PubMed

Hoernke, Maria; Schwieger, Christian; Kerth, Andreas; Blume, Alfred

2012-07-01

Basic amino acids play a key role in the binding of membrane associated proteins to negatively charged membranes. However, side chains of basic amino acids like lysine do not only provide a positive charge, but also a flexible hydrocarbon spacer that enables hydrophobic interactions. We studied the influence of hydrophobic contributions to the binding by varying the side chain length of pentapeptides with ammonium groups starting with lysine to lysine analogs with shorter side chains, namely omithine (Orn), alpha, gamma-diaminobutyric acid (Dab) and alpha, beta-diaminopropionic acid (Dap). The binding to negatively charged phosphatidylglycerol (PG) membranes was investigated by calorimetry, FT-infrared spectroscopy (FT-IR) and monolayer techniques. The binding was influenced by counteracting and sometimes compensating contributions. The influence of the bound peptides on the lipid phase behavior depends on the length of the peptide side chains. Isothermal titration calorimetry (ITC) experiments showed exothermic and endothermic effects compensating to a different extent as a function of side chain length. The increase in lipid phase transition temperature was more significant for peptides with shorter side chains. FTIR-spectroscopy revealed changes in hydration of the lipid bilayer interface after peptide binding. Using monolayer techniques, the contributions of electrostatic and hydrophobic effects could clearly be observed. Peptides with short side chains induced a pronounced decrease in surface pressure of PG monolayers whereas peptides with additional hydrophobic interactions decreased the surface pressure much less or even lead to an increase, indicating insertion of the hydrophobic part of the side chain into the lipid monolayer.

The effect on colon visualization during colonoscopy of the addition of simethicone to polyethylene glycol-electrolyte solution: a randomized single-blind study.

PubMed

Matro, Rebecca; Tupchong, Keegan; Daskalakis, Constantine; Gordon, Victoria; Katz, Leo; Kastenberg, David

2012-11-29

Colonic bubbles associated with polyethylene glycol-electrolyte solution (PEG-ELS) are common and obscure mucosal visualization. This study aimed to determine whether adding simethicone decreases the incidence of bubbles. Prospective, single-blind, randomized comparison of split dose PEG-ELS vs. PEG-ELS+simethicone (PEG-S) for outpatient colonoscopy. Bubble severity for colonic segments was assessed on withdrawal as A=no/minimal bubbles, B=moderate bubbles/interfere with detecting 5 mm polyp, C=severe bubbles/interfere with detecting 10 mm polyp. Primary end point was Grade B or C bubbles in any colon segment. Secondary end points were cleansing quality, incidence and severity of side effects, and polyp detection. One hundred and thirty nine patients enrolled; 13 withdrew before colonoscopy. Of 123 patients evaluated, 62 took PEG-S and 61 PEG-ELS. The incidence of grade B or C bubbles was much lower with PEG-S compared with PEG-ELS (2% vs. 38%; P=0.001). Overall cleansing (excellent or good) quality was not significantly different for either the whole colon (89% PEG-ELS, 94% of PEG-S, P=0.529) or right colon (88% PEG-ELS, 94% PEG-S, P=0.365). More PEG-S patients had excellent rather than good preps (whole colon 53% vs. 28%, P=0.004; right colon 53% vs. 35%, P=0.044). Need for any flushing was less with PEG-S (38% vs. 70%, P=0.001). The groups were not significantly different with respect to total procedure and withdrawal times, incidence or severity of side effects, or number of polyps/patient or adenomas/patient. Adding simethicone to PEG-ELS effectively eliminates bubbles, substantially reduces the need for flushing, and results in more excellent preparations.

The Effect on Colon Visualization During Colonoscopy of the Addition of Simethicone to Polyethylene Glycol-Electrolyte Solution: A Randomized Single-Blind Study

PubMed Central

Matro, Rebecca; Tupchong, Keegan; Daskalakis, Constantine; Gordon, Victoria; Katz, Leo; Kastenberg, David

2012-01-01

OBJECTIVES: Colonic bubbles associated with polyethylene glycol-electrolyte solution (PEG-ELS) are common and obscure mucosal visualization. This study aimed to determine whether adding simethicone decreases the incidence of bubbles. METHODS: Prospective, single-blind, randomized comparison of split dose PEG-ELS vs. PEG-ELS+simethicone (PEG-S) for outpatient colonoscopy. Bubble severity for colonic segments was assessed on withdrawal as A=no/minimal bubbles, B=moderate bubbles/interfere with detecting 5 mm polyp, C=severe bubbles/interfere with detecting 10 mm polyp. Primary end point was Grade B or C bubbles in any colon segment. Secondary end points were cleansing quality, incidence and severity of side effects, and polyp detection. RESULTS: One hundred and thirty nine patients enrolled; 13 withdrew before colonoscopy. Of 123 patients evaluated, 62 took PEG-S and 61 PEG-ELS. The incidence of grade B or C bubbles was much lower with PEG-S compared with PEG-ELS (2% vs. 38% P=0.001). Overall cleansing (excellent or good) quality was not significantly different for either the whole colon (89% PEG-ELS, 94% of PEG-S, P=0.529) or right colon (88% PEG-ELS, 94% PEG-S, P=0.365). More PEG-S patients had excellent rather than good preps (whole colon 53% vs. 28%, P=0.004; right colon 53% vs. 35%, P=0.044). Need for any flushing was less with PEG-S (38% vs. 70%, P=0.001). The groups were not significantly different with respect to total procedure and withdrawal times, incidence or severity of side effects, or number of polyps/patient or adenomas/patient. CONCLUSIONS: Adding simethicone to PEG-ELS effectively eliminates bubbles, substantially reduces the need for flushing, and results in more excellent preparations. PMID:23238113

Leaf wax n-alkane distributions in and across modern plants: Implications for paleoecology and chemotaxonomy

NASA Astrophysics Data System (ADS)

Bush, Rosemary T.; McInerney, Francesca A.

2013-09-01

Long chain (C21 to C37) n-alkanes are among the most long-lived and widely utilized terrestrial plant biomarkers. Dozens of studies have examined the range and variation of n-alkane chain-length abundances in modern plants from around the world, and n-alkane distributions have been used for a variety of purposes in paleoclimatology and paleoecology as well as chemotaxonomy. However, most of the paleoecological applications of n-alkane distributions have been based on a narrow set of modern data that cannot address intra- and inter-plant variability. Here, we present the results of a study using trees from near Chicago, IL, USA, as well as a meta-analysis of published data on modern plant n-alkane distributions. First, we test the conformity of n-alkane distributions in mature leaves across the canopy of 38 individual plants from 24 species as well as across a single growing season and find no significant differences for either canopy position or time of leaf collection. Second, we compile 2093 observations from 86 sources, including the new data here, to examine the generalities of n-alkane parameters such as carbon preference index (CPI), average chain length (ACL), and chain-length ratios for different plant groups. We show that angiosperms generally produce more n-alkanes than do gymnosperms, supporting previous observations, and furthermore that CPI values show such variation in modern plants that it is prudent to discard the use of CPI as a quantitative indicator of n-alkane degradation in sediments. We also test the hypotheses that certain n-alkane chain lengths predominate in and therefore can be representative of particular plant groups, namely, C23 and C25 in Sphagnum mosses, C27 and C29 in woody plants, and C31 in graminoids (grasses). We find that chain-length distributions are highly variable within plant groups, such that chemotaxonomic distinctions between grasses and woody plants are difficult to make based on n-alkane abundances. In contrast, Sphagnum mosses are marked by their predominance of C23 and C25, chain lengths which are largely absent in terrestrial vascular plants. The results here support the use of C23 as a robust proxy for Sphagnum mosses in paleoecological studies, but not the use of C27, C29, and C31 to separate graminoids and woody plants from one another, as both groups produce highly variable but significant amounts of all three chain lengths. In Africa, C33 and C35 chain lengths appear to distinguish graminoids from some woody plants, but this may be a reflection of the differences in rainforest and savanna environments. Indeed, variation in the abundances of long n-alkane chain lengths may be responding in part to local environmental conditions, and this calls for a more directed examination of the effects of temperature and aridity on plant n-alkane distributions in natural environments.

Addition of simethicone improves small bowel capsule endoscopy visualisation quality.

PubMed

Krijbolder, M S; Grooteman, K V; Bogers, S K; de Jong, D J

2018-01-01

Small bowel capsule endoscopy (SBCE) is an important diagnostic tool for small-bowel diseases but its quality may be hampered by intraluminal gas. This study evaluated the added value of the anti-foaming agent, simethicone, to a bowel preparation with polyethylene glycol (PEG) on the quality of small bowel visualisation and its use in the Netherlands. This was a retrospective, single-blind, cohort study. Patients in the PEG group only received PEG prior to SBCE. Patients in the PEG-S group ingested additional simethicone. Two investigators assessed the quality of small-bowel visualisation using a four-point scale for 'intraluminal gas' and 'faecal contamination'. By means of a survey, the use of anti-foaming agents was assessed in a random sample of 16 Dutch hospitals performing SBCE. The quality of small bowel visualisation in the PEG group (n = 33) was significantly more limited by intraluminal gas when compared with the PEG-S group (n = 31): proximal segment 83.3% in PEG group vs. 18.5% in PEG-S group (p < 0.01), distal segment 66.7% vs. 18.5% respectively (p < 0.01). No difference was observed in the amount of faecal contamination (proximal segment 80.0% PEG vs. 59.3% PEG-S, p = 0.2; distal segment 90.0% PEG vs. 85.2% PEG-S, p = 0.7), mean small bowel transit times (4.0 PEG vs. 3.9 hours PEG-S, p = 0.7) and diagnostic yield (43.3% PEG vs. 22.2% PEG-S, p = 0.16). Frequency of anti-foaming agent use in the Netherlands was low (3/16, 18.8%). Simethicone is of added value to a PEG bowel preparation in improving the quality of visualisation of the small bowel by reducing intraluminal gas. At present, the use of anti-foaming agents in SBCE preparation is not standard practice in the Netherlands.

Theory of polyelectrolytes in solvents.

PubMed

Chitanvis, Shirish M

2003-12-01

Using a continuum description, we account for fluctuations in the ionic solvent surrounding a Gaussian, charged chain and derive an effective short-ranged potential between the charges on the chain. This potential is repulsive at short separations and attractive at longer distances. The chemical potential can be derived from this potential. When the chemical potential is positive, it leads to a meltlike state. For a vanishingly low concentration of segments, this state exhibits scaling behavior for long chains. The Flory exponent characterizing the radius of gyration for long chains is calculated to be approximately 0.63, close to the classical value obtained for second order phase transitions. For short chains, the radius of gyration varies linearly with N, the chain length, and is sensitive to the parameters in the interaction potential. The linear dependence on the chain length N indicates a stiff behavior. The chemical potential associated with this interaction changes sign, when the screening length in the ionic solvent exceeds a critical value. This leads to condensation when the chemical potential is negative. In this state, it is shown using the mean-field approximation that spherical and toroidal condensed shapes can be obtained. The thickness of the toroidal polyelectrolyte is studied as a function of the parameters of the model, such as the ionic screening length. The predictions of this theory should be amenable to experimental verification.