Synthesis of poly(N-isopropylacrylamide) particles for metal affinity binding of peptides

PubMed Central

Tsai, Hsin-Yi; Lee, Alexander; Peng, Wei; Yates, Matthew Z.

2013-01-01

Temperature-sensitive poly(N-isopropylacrylamide) (PNIPAM) microgel particles with metal affinity ligands were prepared for selective binding of peptides containing the His6-tag (six consecutive histidine residues). The PNIPAM particles were copolymerized with the functional ligand vinylbenzyl iminodiacetic acid (VBIDA) through a two-stage dispersion polymerization using poly(N-vinyl pyrrolidone) (PVP) as a steric stabilizer. The resulting particles were monodisperse in size and colloidally stable over a wide range of temperature and ionic strength due to chemically grafted PVP chains. The particle size was also found to be sensitive to ionic strength and pH of the aqueous environment, likely due to the electrostatic repulsion between ionized VBIDA groups. Divalent nickel ions were chelated to the VBIDA groups, allowing selective metal affinity attachment of a His6-Cys peptide. The peptide was released upon the addition of the competitive ligand imidazole, demonstrating that the peptide attachment to the particles is reversible and selective. PMID:24176889

Controlled Synthesis and Fluorescence Tracking of Highly Uniform Poly(N-isopropylacrylamide) Microgels.

PubMed

Virtanen, Otto L J; Purohit, Ashvini; Brugnoni, Monia; Wöll, Dominik; Richtering, Walter

2016-09-08

Stimuli-sensitive poly(N-isopropylacrylamide) (PNIPAM) microgels have various prospective practical applications and uses in fundamental research. In this work, we use single particle tracking of fluorescently labeled PNIPAM microgels as a showcase for tuning microgel size by a rapid non-stirred precipitation polymerization procedure. This approach is well suited for prototyping new reaction compositions and conditions or for applications that do not require large amounts of product. Microgel synthesis, particle size and structure determination by dynamic and static light scattering are detailed in the protocol. It is shown that the addition of functional comonomers can have a large influence on the particle nucleation and structure. Single particle tracking by wide-field fluorescence microscopy allows for an investigation of the diffusion of labeled tracer microgels in a concentrated matrix of non-labeled microgels, a system not easily investigated by other methods such as dynamic light scattering.

Segregation of mass at the periphery of N -isopropylacrylamide-co-acrylic-acid microgels at high temperatures

DOE PAGES

Hyatt, John S.; Do, Changwoo; Hu, Xiaobo; ...

2015-09-29

Here, we investigate poly(N-isopropylacrylamide) (pNIPAM) microgels randomly copolymerized with large mol % of protonated acrylic acid (AAc), finding that above the lower critical solution temperature the presence of the acid strongly disrupts pNIPAM's collapse, leading to unexpected new behavior at high temperatures. We see a dramatic increase in the ratio between the radius of gyration and the hydrodynamic radius above the theoretical value for homogeneous spheres, and a corresponding increase of the network length scale, which we attribute to the presence of a heterogeneous polymer distribution that forms due to frustration of pNIPAM's coil-to-globule transition by the AAc. Finally, wemore » analyze this phenomenon using a Debye-Bueche-like scattering contribution as opposed to the Lorentzian term often used, interpreting the results in terms of mass segregation at the particle periphery.« less

In vitro behavior of human mesenchymal stem cells on poly(N-isopropylacrylamide) based biointerfaces obtained by matrix assisted pulsed laser evaporation

NASA Astrophysics Data System (ADS)

Icriverzi, Madalina; Rusen, Laurentiu; Sima, Livia Elena; Moldovan, Antoniu; Brajnicov, Simona; Bonciu, Anca; Mihailescu, Natalia; Dinescu, Maria; Cimpean, Anisoara; Roseanu, Anca; Dinca, Valentina

2018-05-01

The use of smart coatings with tunable characteristics in bioengineering fields is directly correlated with the surface chemical and topographical properties, the method of preparation, and also with the type of cells implied for the specific application. In this work, a versatile surface modification technique based on the use of lasers (Matrix-Assisted Pulsed Laser Evaporation (MAPLE)) was used to yield poly(N-isopropylacrylamide) (pNIPAM) and its derivatives (amine, azide and amide terminated pNIPAM) functional and termoresponsive thin films. Surface properties of pNIPAM and its derivative films such as morphology, roughness and hydrophobic/hydrophilic character, as well as the thermoresponsive capacity were investigated by atomic force microscopy and contact angle measurements. The chemical characteristics of the pNIPAM based thin films were analysed by Fourier Transform Infrared Spectroscopy (FTIR). The chemical functionality was kept for all the samples obtained by MAPLE and the thermoresponse was demonstrated by the change in the contact angle and thickness values when the temperature was shifted from 37 °C to 24 °C for all the materials tested, with a smaller change for maleimide terminated pNIPAM. Biological assays performed in vitro (fluorescence microscopy and Scanning Electron Microscopy (SEM)) confirmed the conditioning of the early mesenchymal stem cell (MSC) growth by specific chemistry of the coatings. The cell imaging analysis revealed no cytotoxic effect of pNIPAM surfaces irrespective of type of functionalization. An increased proliferation rate of the cells grown on pNIPAM-azide surfaces and a lower cell density on pNIPAM-maleimide surfaces compared to the pNIPAM surfaces was observed, which can direct their use to potential surfaces in regenerative medicine approaches.

Physics in ordered and disordered colloidal matter composed of poly(N-isopropylacrylamide) microgel particles.

PubMed

Yunker, Peter J; Chen, Ke; Gratale, Matthew D; Lohr, Matthew A; Still, Tim; Yodh, A G

2014-05-01

This review collects and describes experiments that employ colloidal suspensions to probe physics in ordered and disordered solids and related complex fluids. The unifying feature of this body of work is its clever usage of poly(N-isopropylacrylamide) (PNIPAM) microgel particles. These temperature-sensitive colloidal particles provide experimenters with a 'knob' for in situ control of particle size, particle interaction and particle packing fraction that, in turn, influence the structural and dynamical behavior of the complex fluids and solids. A brief summary of PNIPAM particle synthesis and properties is given, followed by a synopsis of current activity in the field. The latter discussion describes a variety of soft matter investigations including those that explore formation and melting of crystals and clusters, and those that probe structure, rearrangement and rheology of disordered (jammed/glassy) and partially ordered matter. The review, therefore, provides a snapshot of a broad range of physics phenomenology which benefits from the unique properties of responsive microgel particles.

Highly Swellable, Dual-Responsive Hydrogels Based on PNIPAM and Redox Active Poly(ferrocenylsilane) Poly(ionic liquid)s: Synthesis, Structure, and Properties.

PubMed

Feng, Xueling; Zhang, Kaihuan; Chen, Peng; Sui, Xiaofeng; Hempenius, Mark A; Liedberg, Bo; Vancso, G Julius

2016-12-01

Highly swellable, dual-responsive hydrogels, consisting of thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) and redox-responsive poly(ferrocenylsilane) (PFS) based poly(ionic liquid)s (PILs) are formed by photo-polymerization. PFS chains bearing cross-linkable vinylimidazolium (VIm) side groups are copolymerized with NIPAM in aqueous solutions under ultraviolet light (λ = 365 nm) in the presence of a photoinitiator. The PFS-PILs serve as a macro-cross-linker and also provide redox responsiveness. The swelling ratio, morphology, and lower critical solution temperature (LCST) of the hydrogels are studied as a function of the PNIPAM/PFS ratio. The value of the LCST is dependent on the choice of the counterion of the PIL and the PNIPAM/PFS ratio. The hydrogel is employed as a reducing environment for the in situ fabrication of gold nanoparticles (AuNPs), forming AuNP-hydrogel composites. The localized surface plasmon resonance peak of the as-synthesized Au nanoparticles inside the hydrogel could be tuned by altering the temperature. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The modulation of physicochemical characterization of innovative liposomal platforms: the role of the grafted thermoresponsive polymers.

PubMed

Chountoulesi, Maria; Kyrili, Aimilia; Pippa, Natassa; Meristoudi, Anastasia; Pispas, Stergios; Demetzos, Costas

2017-05-01

This study is focused on chimeric advanced drug delivery systems and specifically on thermosensitive liposomes, combining lipids and thermoresponsive polymers. In this investigation, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) chimeric liposomal systems were prepared, incorporating the homopolymer C 12 H 25 -poly(N-isopropylacrylamide)-COOH (C 12 H 25 -PNIPAM-COOH) and the block copolymer poly(n-butylacrylate-b-N-isoropylacrylamide) (PnBA-PNIPAM), at six different molar ratios. Both of these polymers contain the thermoresponsive PNIPAM block, which exhibits lower critical solution temperature (LCST) at 32 °C in aqueous solutions, changing its nature from hydrophilic to hydrophobic above LCST. During the preparation of liposomes, the dispersions were observed visually, while after the preparation we studied the alterations of the physicochemical characteristics, by measuring the size, size distribution and ζ-potential of prepared liposomes. The presence of polymer, either C 12 H 25 -PNIPAM-COOH or PnBA-PNIPAM, resulted in liposomes exhibiting different physicochemical characteristics in comparison to conventional DPPC liposomes. At the highest percentage of the polymeric guest, chimeric liposomes were found to retain their size during the stability studies. The incorporation of the appropriate amount of these novel thermoresponsive polymers yields liposomal stabilization and imparts thermoresponsiveness, due to the functional PNIPAM block.

Single chain structure of a poly(N-isopropylacrylamide) surfactant in water.

PubMed

Abbott, Lauren J; Tucker, Ashley K; Stevens, Mark J

2015-03-05

We present atomistic simulations of a single PNIPAM-alkyl copolymer surfactant in aqueous solution at temperatures below and above the LCST of PNIPAM. We compare properties of the surfactant with pure PNIPAM oligomers of similar lengths, such as the radius of gyration and solvent accessible surface area, to determine the differences in their structures and transition behavior. We also explore changes in polymer-polymer and polymer-water interactions, including hydrogen bond formation. The expected behavior is observed in the pure PNIPAM oligomers, where the backbone folds onto itself above the LCST in order to shield the hydrophobic groups from water. The surfactant, on the other hand, does not show much conformational change as a function of temperature, but instead folds to bring the hydrophobic alkyl tail and PNIPAM headgroup together at all temperatures. The atomic detail available from these simulations offers important insight into understanding how the transition behavior is changed in PNIPAM-based systems.

Two-Dimensional Micropatterns of Self-Assembled Poly(N-isopropylacrylamide) Microgels for Patterned Adhesion and Temperature-Responsive Detachment of Fibroblasts

PubMed Central

Tsai, Hsin-Yi; Vats, Kanika; Yates, Matthew Z.; Benoit, Danielle S. W.

2013-01-01

Thermoresponsive poly(N-isopropyl acrylamide) (PNIPAM) microgels were patterned on polystyrene substrates via dip coating, creating cytocompatible substrates that provided spatial control over cell adhesion. This simple dip coating method, which exploits variable substrate withdrawal speeds form particle suspension formed stripes of densely-packed PNIPAM microgels, while spacings between the stripes contained sparsely-distributed PNIPAM microgels. The assembly of three different PNIPAM microgel patterns, namely patterns composed of 50 μm stripes/50 μm spacings, 50 μm stripes/100 μm spacings, and 100 μm stripes/100 μm spacings was verified using high-resolution optical micrographs and ImageJ analysis. PNIPAM microgels existed as monolayers within stripes and spacings, as revealed by atomic force microscopy (AFM). Upon cell seeding on PNIPAM micropatterned substrates, NIH3T3 fibroblast cells preferentially adhered within spacings to form cell patterns. Three days after cell seeding, cells proliferated to form confluent cell layers. The thermoresponsiveness of the underlying PNIPAM microgels was then utilized to recover fibroblast cell sheets from substrates simply by lowering the temperature, without disrupting the underlying PNIPAM microgel patterns. Harvested cell sheets similar to these have been used for multiple tissue engineering applications. Also, this simple, low cost, template-free dip coating technique can be utilized to micropattern multifunctional PNIPAM microgels, generating complex stimuli-responsive substrates to study cell-material interactions and allow drug delivery to cells in a spatially and temporally-controlled manners. PMID:23968193

Polymer Inverse Temperature-Dependent Solubility: A Visual Demonstration of the Importance of "T[Delta]S" in the Gibbs Equation

ERIC Educational Resources Information Center

Bergbreiter, David E.; Mijalis, Alexander J.; Fu, Hui

2012-01-01

Reversible polymer dehydration and precipitation from water due to the unfavorable entropy of hydration is examined using a melting-point apparatus. The thermoresponsive lower critical solution temperature (LCST) behavior of poly(N-isopropylacrylamide) (PNIPAM) is responsible for these effects. An experiment is described that allows students to…

Hydrostatic pressure effect on PNIPAM cononsolvency in water-methanol solutions.

PubMed

Pica, Andrea; Graziano, Giuseppe

2017-12-01

When methanol is added to water at room temperature and 1atm, poly (N-isopropylacrylamide), PNIPAM, undergoes a coil-to-globule collapse transition. This intriguing phenomenon is called cononsolvency. Spectroscopic measurements have shown that application of high hydrostatic pressure destroys PNIPAM cononsolvency in water-methanol solutions. We have developed a theoretical approach that identifies the decrease in solvent-excluded volume effect as the driving force of PNIPAM collapse on increasing the temperature. The same approach indicates that cononsolvency, at room temperature and P=1atm, is caused by the inability of PNIPAM to make all the attractive energetic interactions that it could be engaged in, due to competition between water and methanol molecules. The present analysis suggests that high hydrostatic pressure destroys cononsolvency because the coil state becomes more compact, and the quantity measuring PNIPAM-solvent attractions increases in magnitude due to the solution density increase, and the ability of small water molecules to substitute methanol molecules on PNIPAM surface. Copyright © 2017 Elsevier B.V. All rights reserved.

On the molecular origin of the cooperative coil-to-globule transition of poly(N-isopropylacrylamide) in water.

PubMed

Tavagnacco, L; Zaccarelli, E; Chiessi, E

2018-04-18

By means of atomistic molecular dynamics simulations we investigate the behaviour of poly(N-isopropylacrylamide), PNIPAM, in water at temperatures below and above the lower critical solution temperature (LCST), including the undercooled regime. The transition between water soluble and insoluble states at the LCST is described as a cooperative process involving an intramolecular coil-to-globule transition preceding the aggregation of chains and the polymer precipitation. In this work we investigate the molecular origin of such cooperativity and the evolution of the hydration pattern in the undercooled polymer solution. The solution behaviour of an atactic 30-mer at high dilution is studied in the temperature interval from 243 to 323 K with a favourable comparison to available experimental data. In the water soluble states of PNIPAM we detect a correlation between polymer segmental dynamics and diffusion motion of bound water, occurring with the same activation energy. Simulation results show that below the coil-to-globule transition temperature PNIPAM is surrounded by a network of hydrogen bonded water molecules and that the cooperativity arises from the structuring of water clusters in proximity to hydrophobic groups. Differently, the perturbation of the hydrogen bond pattern involving water and amide groups occurs above the transition temperature. Altogether these findings reveal that even above the LCST PNIPAM remains largely hydrated and that the coil-to-globule transition is related with a significant rearrangement of the solvent in the proximity of the surface of the polymer. The comparison between the hydrogen bonding of water in the surrounding of PNIPAM isopropyl groups and in the bulk displays a decreased structuring of solvent at the hydrophobic polymer-water interface across the transition temperature, as expected because of the topological extension along the chain of such interface. No evidence of an upper critical solution temperature behaviour, postulated in theoretical and thermodynamics studies of PNIPAM aqueous solution, is observed in the low temperature domain.

Thermo-responsive and compression properties of TEMPO-oxidized cellulose nanofiber-modified PNIPAm hydrogels.

PubMed

Wei, Jinguang; Chen, Yufei; Liu, Hongzhi; Du, Chungui; Yu, Huilong; Zhou, Zhongxi

2016-08-20

In this study, TEMPO-oxidized bamboo cellulose nanofibers (TO-CNF) with anionic carboxylate groups on the surfaces were in-situ incorporated into poly(N-isopropylacrylamide) (PNIPAm) matrix to improve its thermo-responsive and mechanical properties during the polymerization. The microstructure, swelling behaviors, and compressive strength of resultant PNIPAm composite hydrogels with varying contents of TO-CNFs (0-10wt%) were then examined, respectively. Modified hydrogels exhibited the similar light transparency to pure PNIPAm one due to the formation of semi-IPN structure between PNIPAm and TO-CNF. FT-IR spectra demonstrated that the presence of TO-CNF did not alter the position of characteristic peaks associated with PNIPAm. SEM observation suggested that the pore size of PNIPAm hydrogels was markedly increased after the incorporation of TO-CNF. Also, the composite hydrogels showed superior swelling behavior and much improved compression properties with respect to pure PNIPAm one. Thus, TO-CNF appeared to be a "green" nanofiller that can simultaneously improve swelling and mechanical properties of PNIPAm hydrogel. Copyright © 2016 Elsevier Ltd. All rights reserved.

Thermo-Responsive Amphiphilic Block Copolymers Stablilized Gold Nanoparticles: Synthesis and High Catalytic Properties.

PubMed

Lü, Jianhua; Yang, Yu; Gao, Junfang; Duan, Haichao; Lü, Changli

2018-06-19

A series of novel well-defined 8-hydroxyquinoline (HQ)-containing thermo-responsive amphiphilic diblock copolymers poly(styrene-co-5-(2-methacryloylethyloxy- methyl)-8-quinolinol)-b-poly(N-isopropylacrylamide) P(St-co-MQ)-b-PNIPAm (P1,2), P(NIPAm- co-MQ)-b-PSt (P3,4) and triblock copolymer poly(N-isopropylacrylamide)-b-poly(methyl- methacrylate-co-5-(2-methacryloylethyloxymethyl)-8-quinolinol)-b-polystyrene PNIPAm-b- P(MMA-co-MQ)-b-PSt (P5) were prepared by reversible addition fragmentation chain transfer (RAFT) polymerization, and their self-assembly behaviors were studied. The block copolymers P1-P5 stabilized gold nanoparticles (Au@P1-Au@P5) with small size and narrow distribution were obtained through in situ reduction of gold precursors in aqueous solution of polymer micelles with HQ as the coordination groups. The resulting Au@P nanohybrids possessed excellent catalytic activities for the reduction of nitrophenols using NaBH4. The size, morphology and surface chemistry of Au NPs could be controlled by adjusting the structure of block polymers with HQ in different block positions, which plays an important role in the catalytic properties. It was found that longer chain length of hydrophilic or hydrophobic segments of block copolymers were beneficial to elevate the catalytic activity of Au NPs for the reduction of nitrophenols, and the spherical nanoparticles (Au@P5) stabilized with triblock copolymer exhibit higher catalytic performance. Surprisingly, the gold nanowires (Au@P4) produced with P4 have a highest catalytic activity due to large abundance of grain boundaries. Excellent thermo-responsive behaviors for catalytic reaction make the as-prepared Au@P hybrids become an environmentally responsive nano-catalytic materials.

Antimicrobial activity of silver nanoparticles encapsulated in poly-N-isopropylacrylamide-based polymeric nanoparticles.

PubMed

Qasim, Muhammad; Udomluck, Nopphadol; Chang, Jihyun; Park, Hansoo; Kim, Kyobum

2018-01-01

In this study, we analyzed the antimicrobial activities of poly- N -isopropylacrylamide (pNIPAM)-based polymeric nanoparticles encapsulating silver nanoparticles (AgNPs). Three sizes of AgNP-encapsulating pNIPAM- and pNIPAM-NH 2 -based polymeric nanoparticles were fabricated. Highly stable and uniformly distributed AgNPs were encapsulated within polymeric nanoparticles via in situ reduction of AgNO 3 using NaBH 4 as the reducing agent. The formation and distribution of AgNPs was confirmed by UV-visible spectroscopy, transmission electron microscopy, and inductively coupled plasma optical emission spectrometry, respectively. Both polymeric nanoparticles showed significant bacteriostatic activities against Gram-negative ( Escherichia coli ) and Gram-positive ( Staphylococcus aureus ) bacteria depending on the nanoparticle size and amount of AgNO 3 used during fabrication.

Antimicrobial activity of silver nanoparticles encapsulated in poly-N-isopropylacrylamide-based polymeric nanoparticles

PubMed Central

Qasim, Muhammad; Udomluck, Nopphadol; Chang, Jihyun; Park, Hansoo; Kim, Kyobum

2018-01-01

In this study, we analyzed the antimicrobial activities of poly-N-isopropylacrylamide (pNIPAM)-based polymeric nanoparticles encapsulating silver nanoparticles (AgNPs). Three sizes of AgNP-encapsulating pNIPAM- and pNIPAM-NH2-based polymeric nanoparticles were fabricated. Highly stable and uniformly distributed AgNPs were encapsulated within polymeric nanoparticles via in situ reduction of AgNO3 using NaBH4 as the reducing agent. The formation and distribution of AgNPs was confirmed by UV-visible spectroscopy, transmission electron microscopy, and inductively coupled plasma optical emission spectrometry, respectively. Both polymeric nanoparticles showed significant bacteriostatic activities against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria depending on the nanoparticle size and amount of AgNO3 used during fabrication. PMID:29379284

Synthesis and Characterization of Poly(Ethylene Glycol) Based Thermo-Responsive Hydrogels for Cell Sheet Engineering.

PubMed

Son, Kuk Hui; Lee, Jin Woo

2016-10-20

The swelling properties and thermal transition of hydrogels can be tailored by changing the hydrophilic-hydrophobic balance of polymer networks. Especially, poly( N -isopropylacrylamide) (PNIPAm) has received attention as thermo-responsive hydrogels for tissue engineering because its hydrophobicity and swelling property are transited around body temperature (32 °C). In this study, we investigated the potential of poly(ethylene glycol) diacrylate (PEGDA) as a hydrophilic co-monomer and crosslinker of PNIPAm to enhance biological properties of PNIPAm hydrogels. The swelling ratios, lower critical solution temperature (LCST), and internal pore structure of the synthesized p(NIPAm- co -PEGDA) hydrogels could be varied with changes in the molecular weight of PEGDA and the co-monomer ratios (NIPAm to PEGDA). We found that increasing the molecular weight of PEGDA showed an increase of pore sizes and swelling ratios of the hydrogels. In contrast, increasing the weight ratio of PEGDA under the same molecular weight condition increased the crosslinking density and decreased the swelling ratios of the hydrogels. Further, to evaluate the potential of these hydrogels as cell sheets, we seeded bovine chondrocytes on the p(NIPAm- co -PEGDA) hydrogels and observed the proliferation of the seed cells and their detachment as a cell sheet upon a decrease in temperature. Based on our results, we confirmed that p(NIPAm- co -PEGDA) hydrogels could be utilized as cell sheets with enhanced cell proliferation performance.

Why does high pressure destroy co-non-solvency of PNIPAm in aqueous methanol?

PubMed

de Oliveira, Tiago E; Netz, Paulo A; Mukherji, Debashish; Kremer, Kurt

2015-11-28

It is well known that poly(N-isopropylacrylamide) (PNIPAm) exhibits an interesting, yet puzzling, phenomenon of co-non-solvency. Co-non-solvency occurs when two competing good solvents for PNIPAm, such as water and alcohol, are mixed together. As a result, the same PNIPAm collapses within intermediate mixing ratios. This complex conformational transition is driven by preferential binding of methanol with PNIPAm. Interestingly, co-non-solvency can be destroyed when applying high hydrostatic pressures. In this work, using a large scale molecular dynamics simulation employing high pressures, we propose a microscopic picture behind the suppression of the co-non-solvency phenomenon. Based on thermodynamic and structural analysis, our results suggest that the preferential binding of methanol with PNIPAm gets partially lost at high pressures, making the background fluid reasonably homogeneous for the polymer. This is consistent with the hypothesis that the co-non-solvency phenomenon is driven by preferential binding and is not based on depletion effects.

Poly-N-isopropylacrylamide (pNIPAM): a reversible bioadhesive for sclerotomy closure.

PubMed

Lima, Luiz H; Morales, Yael; Cabral, Thiago

2016-01-01

To determine the safety and efficacy of poly- N -isopropylacrylamide, a thermoresponsive adhesive, for sutureless sclerotomy closure in rabbits. Eight rabbits were randomized into three groups: short-term acute, mid-term chronic, and long-term chronic studies. A corresponding control group in which the scleral wounds were sutured by 6-0 vicryl sutures was assigned for each study group. A 20-gauge sclerotomy was performed following a core vitrectomy and 0.1 mL of 50 % liquid poly- N -isopropylacrylamide was applied to the scleral wounds. Before the polymer application, the scleral surface was raised above 32 °C using a halogen bulb lamp. Follow-up exams included color external and fundus photography, fundus fluorescein angiography, optical coherence tomography, and electroretinography. After the last follow-up assessment, the rabbits were sacrificed and histopathological studies on the scleral incision sites were performed. Scleral wound healing was observed in the long-term chronic study rabbits. Histological studies were able to identify poly- N -isopropylacrylamide polymer at the sclerotomy site in the mid-term chronic study rabbits. Besides iatrogenic cataracts due to mechanical instrument touch in 2 rabbits, no other ocular abnormalities were identified in any of the eyes in the perioperative setting or during the follow-up period. Cornea, retina, and vitreous remained unaffected, and no abnormal inflammatory reaction or endophthalmitis was noticed in the 3 study groups. Filtering blebs indicative of leakage through the sclerotomies were not observed during the follow-up period. Poly- N -isopropylacrylamide may provide effective in vitro scleral adhesion above 32 °C. Clinical studies are required to evaluate its utility in patients undergoing pars plana vitrectomy.

Thermo-responsive in-situ forming hydrogels as barriers to prevent post-operative peritendinous adhesion.

PubMed

Chou, Pang-Yun; Chen, Shih-Heng; Chen, Chih-Hao; Chen, Shih-Hsien; Fong, Yi Teng; Chen, Jyh-Ping

2017-11-01

In this study, we aimed to assess whether thermo-responsive in-situ forming hydrogels based on poly(N-isopropylacrylamide) (PNIPAM) could prevent post-operative peritendinous adhesion. The clinical advantages of the thermo-responsive hydrogels are acting as barrier material to block penetration of fibroblasts, providing mobility and flexibility during application and enabling injection through a small opening to fill spaces of any shape after surgery. The thermo-responsiveness of hydrogels was determined to ensure their clinic uses. By grafting hydrophilic biopolymers chitosan (CS) and hyaluronic acid (HA) to PNIPAM, the copolymer hydrogels show enhanced water retention and lubrication, while reduced volume shrinkage during phase transition. In cell culture experiments, the thermo-responsive hydrogel has good biocompatibility and reduces fibroblast penetration. In animal experiments, the effectiveness of preventing post-operative peritendinous adhesion was studied in a rabbit deep flexor tendon model. From gross examination, histology, bending angles of joints, tendon gliding excursion and pull-out force, HA-CS-PNIPAM (HACPN) was confirmed to be the best barrier material to prevent post-operative peritendinous adhesion compared to PNIPAM and CS-PNIPAM (CPN) hydrogels and a commercial barrier film Seprafilm®. There was no significant difference in the breaking strength of HACPN-treated tendons and spontaneously healed ones, indicating HACPN hydrogel application did not interfere with normal tendon healing. We conclude that HACPN hydrogel can provide the best functional outcomes to significantly prevent post-operative tendon adhesion in vivo. We prepared thermo-responsive in-situ forming hydrogels based on poly(N-isopropylacrylamide) (PNIPAM) to prevent post-operative peritendinous adhesion. The injectable barrier hydrogel could have better anti-adhesive properties than current commercial products by acting as barrier material to block penetration of fibroblasts, providing mobility and flexibility during application and enabling injection through a small opening to fill spaces of any shape after surgery. The effectiveness of preventing post-operative peritendinous adhesion was studied in a rabbit deep flexor tendon model. From gross examination, histology, bending angles of joints, tendon gliding excursion and pull-out force, HA-CS-PNIPAM (HACPN) was confirmed to be the best barrier material to prevent post-operative peritendinous adhesion compared to PNIPAM and CS-PNIPAM (CPN) hydrogels and a commercial barrier film Seprafilm®. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

A smart temperature and magnetic-responsive gating carbon nanotube membrane for ion and protein transportation

PubMed Central

Cong, Hailin; Xu, Xiaodan; Yu, Bing; Yang, Zhaohui; Zhang, Xiaoyan

2016-01-01

Carbon nanotube (CNT) nanoporous membranes based on pre-aligned CNTs have superior nano-transportation properties in biological science. Herein, we report a smart temperature- and temperature-magnetic-responsive CNT nanoporous membrane (CNM) by grafting thermal-sensitive poly(N-isopropylacrylamide) (PNIPAM) and Fe3O4 nanoparticles (Fe3O4-NPs) on the open ends of pre-aligned CNTs with a diameter around 15 nm via surface-initiated atom transfer radical polymerization (SI-ATRP) method. The inner cavity of the modified CNTs in the membrane is designed to be the only path for ion and protein transportation, and its effective diameter with a variation from ~5.7 nm to ~12.4 nm can be reversible tuned by temperature and magnetic field. The PNIPAM modified CNM (PNIPAM-CNM) and PNIPAM magnetic nanoparticles modified CNM (PNIPAM-MAG-CNM) exhibit excellent temperature- or temperature-magnetic-responsive gating property to separate proteins of different sizes. The PNIPAM-CNMs and PNIPAM-MAG-CNMs have potential applications in making artificial cells, biosensors, bioseparation and purification filters. PMID:27535103

Insight into the effect mechanism of urea-induced protein denaturation by dielectric spectroscopy.

PubMed

Zhang, Cancan; Yang, Man; Zhao, Kongshuang

2017-12-06

Dielectric relaxation spectroscopy was applied to study how urea affects the phase transition of a thermosensitive polymer, poly(N-isopropylacrylamide) (PNIPAM), which has been widely used as a protein model. It was found that there is a pronounced relaxation near 10 GHz for the ternary system of PNIPAM in urea aqueous solution. The temperature dependence of dielectric parameters indicates that urea can reduce the lower critical solution temperature (LCST) of PNIPAM, i.e., stabilize the globule state of PNIPAM and collapse the PNIPAM chains. Based on our results, the interaction mechanism of urea on the conformational transition of PNIPAM was presented: urea replaces water molecules directly bonding with PNIPAM and acts as the bridging agent for the adjacent side chains of PNIPAM. Accordingly, the mechanism with which urea denatures protein was deduced. In addition, it is worth mentioning that, from the temperature dependence of the dielectric parameters obtained in the presence of urea, an interesting phenomenon was found in which the effect of urea on PNIPAM seems to take 2 M as a unit. This result may be the reason why urea and TMAO exit marine fishes at a specific ratio of 2 : 1.

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

Hyatt, John S.; Do, Changwoo; Hu, Xiaobo

Here, we investigate poly(N-isopropylacrylamide) (pNIPAM) microgels randomly copolymerized with large mol % of protonated acrylic acid (AAc), finding that above the lower critical solution temperature the presence of the acid strongly disrupts pNIPAM's collapse, leading to unexpected new behavior at high temperatures. We see a dramatic increase in the ratio between the radius of gyration and the hydrodynamic radius above the theoretical value for homogeneous spheres, and a corresponding increase of the network length scale, which we attribute to the presence of a heterogeneous polymer distribution that forms due to frustration of pNIPAM's coil-to-globule transition by the AAc. Finally, wemore » analyze this phenomenon using a Debye-Bueche-like scattering contribution as opposed to the Lorentzian term often used, interpreting the results in terms of mass segregation at the particle periphery.« less

Single Chain Structure of a Poly(N-isopropylacrylamide) Surfactant in Water

DOE PAGES

Abbott, Lauren J.; Tucker, Ashley K.; Stevens, Mark J.

2015-02-10

In this paper, we present atomistic simulations of a single PNIPAM–alkyl copolymer surfactant in aqueous solution at temperatures below and above the LCST of PNIPAM. We compare properties of the surfactant with pure PNIPAM oligomers of similar lengths, such as the radius of gyration and solvent accessible surface area, to determine the differences in their structures and transition behavior. We also explore changes in polymer–polymer and polymer–water interactions, including hydrogen bond formation. The expected behavior is observed in the pure PNIPAM oligomers, where the backbone folds onto itself above the LCST in order to shield the hydrophobic groups from water.more » The surfactant, on the other hand, does not show much conformational change as a function of temperature, but instead folds to bring the hydrophobic alkyl tail and PNIPAM headgroup together at all temperatures. Finally, the atomic detail available from these simulations offers important insight into understanding how the transition behavior is changed in PNIPAM-based systems.« less

On the molecular origin of the cooperative coil-to-globule transition of poly(N-isopropylacrylamide) in water† †Electronic supplementary information (ESI) available: Stereochemistry and initial conformation of PNIPAM 30-mer; pair distribution functions of PNIPAM methyl groups; average time of transitions of dihedral angles; distribution of methyl dihedral angles; temperature dependence of average number of hydration water molecules; correlation between hydrogen bonding of water molecules per repeating unit in the FHS and end to end distance and correlation between PNIPAM–water hydrogen bonding and end to end distance. Time evolution of PNIPAM with the first hydration shell: movie FHSpnipam.avi. See DOI: 10.1039/c8cp00537k

PubMed Central

Zaccarelli, E.

2018-01-01

By means of atomistic molecular dynamics simulations we investigate the behaviour of poly(N-isopropylacrylamide), PNIPAM, in water at temperatures below and above the lower critical solution temperature (LCST), including the undercooled regime. The transition between water soluble and insoluble states at the LCST is described as a cooperative process involving an intramolecular coil-to-globule transition preceding the aggregation of chains and the polymer precipitation. In this work we investigate the molecular origin of such cooperativity and the evolution of the hydration pattern in the undercooled polymer solution. The solution behaviour of an atactic 30-mer at high dilution is studied in the temperature interval from 243 to 323 K with a favourable comparison to available experimental data. In the water soluble states of PNIPAM we detect a correlation between polymer segmental dynamics and diffusion motion of bound water, occurring with the same activation energy. Simulation results show that below the coil-to-globule transition temperature PNIPAM is surrounded by a network of hydrogen bonded water molecules and that the cooperativity arises from the structuring of water clusters in proximity to hydrophobic groups. Differently, the perturbation of the hydrogen bond pattern involving water and amide groups occurs above the transition temperature. Altogether these findings reveal that even above the LCST PNIPAM remains largely hydrated and that the coil-to-globule transition is related with a significant rearrangement of the solvent in the proximity of the surface of the polymer. The comparison between the hydrogen bonding of water in the surrounding of PNIPAM isopropyl groups and in the bulk displays a decreased structuring of solvent at the hydrophobic polymer–water interface across the transition temperature, as expected because of the topological extension along the chain of such interface. No evidence of an upper critical solution temperature behaviour, postulated in theoretical and thermodynamics studies of PNIPAM aqueous solution, is observed in the low temperature domain. PMID:29619464

Gold Nanoparticles Grafted with PLL-b-PNIPAM: Interplay on Thermal/pH Dual-Response and Optical Properties.

PubMed

Li, Hui-Juan; Li, Peng-Yun; Li, Li-Ying; Haleem, Abdul; He, Wei-Dong

2018-04-16

Narrowly distributed poly(l-lysine- b - N -isopropylacrylamide) (PLL- b -PNIPAM) was prepared through ring-opening polymerization of ε-benzyloxycarbonyl-l-lysine N -carboxy-α-amino anhydride and atom transfer radical polymerization of NIPAM, followed with the removal of ε-benzyloxycarbonyl group. Then gold nanoparticles (AuNPs) grafted with PLL- b -PNIPAM (PNIPAM-PLL-AuNPs) were obtained by the reduction of chloroauric acid with sodium citrate in the presence of PLL- b -PNIPAM. PNIPAM-PLL-AuNPs and its precursors were thoroughly characterized by proton magnetic resonance spectroscope, Fourier transform infrared spectroscope, UV-vis spectroscope, transmission electron microscopy, dynamic light scattering, thermogravimetric analysis, and circular dichroism. The obtained PNIPAM-PLL-AuNPs exhibited high colloid stability even at strong alkaline (pH = 12) and acidic (pH = 2) conditions. The thermal and pH dual-responsive behaviors of the grafting PLL- b -PNIPAM chains was observed to be affected by AuNPs, while not for the secondary structure of PLL chains. Correspondingly, the surface plasmon resonance (SPR) of AuNPs was found to be sensitive to both pH value and temperature. A blue shift in the SPR happened both with increasing pH value and increasing temperature. The stimuli-response was reversible in heating-cooling cycles. The gold nanoparticles with both pH and temperature response may have potential applications in biomedical areas and biosensors.

Near-Infrared Trigged Stimulus-Responsive Photonic Crystals with Hierarchical Structures.

PubMed

Lu, Tao; Pan, Hui; Ma, Jun; Li, Yao; Zhu, Shenmin; Zhang, Di

2017-10-04

Stimuli-responsive photonic crystals (PCs) trigged by light would provide a novel intuitive and quantitative method for noninvasive detection. Inspired by the flame-detecting aptitude of fire beetles and the hierarchical photonic structures of butterfly wings, we herein developed near-infrared stimuli-responsive PCs through coupling photothermal Fe 3 O 4 nanoparticles with thermoresponsive poly(N-isopropylacrylamide) (PNIPAM), with hierarchical photonic structured butterfly wing scales as the template. The nanoparticles within 10 s transferred near-infrared radiation into heat that triggered the phase transition of PNIPAM; this almost immediately posed an anticipated effect on the PNIPAM refractive index and resulted in a composite spectrum change of ∼26 nm, leading to the direct visual readout. It is noteworthy that the whole process is durable and stable mainly owing to the chemical bonding formed between PNIPAM and the biotemplate. We envision that this biologically inspired approach could be utilized in a broad range of applications and would have a great impact on various monitoring processes and medical sensing.

Bio-inspired intelligent evaporation modulation in a thermo-sensitive nanogel colloid solution for self-thermoregulation.

PubMed

Huang, Zhi; Liu, Kang; Feng, Yanhui; Zhou, Jun; Zhang, Xinxin

2017-06-28

Intelligent evaporation and temperature modulation plays an important role in self-regulation of living organisms and many industrial applications. Here we demonstrate that a poly(N-isopropylacrylamide) (PNIPAM) nanogel colloid solution can spontaneously and intelligently modulate its evaporation rate with temperature variation, which has a larger evaporation rate than distilled water at a temperature higher than its lower critical solution temperature (LCST) and a smaller evaporation rate at a temperature lower than its LCST. It performs just like human skin. Theoretical analysis based on the thermodynamic derivation reveals that the evaporation rate transition around the LCST may originate from the saturated vapor pressure transition caused by the status transformation of the PNIPAM additives. An intelligent thermoregulation system based on the PNIPAM colloid solution is also demonstrated, illustrating its potential for intelligent temperature control and acting as an artificial skin.

Bioinspired Thermoresponsive Photonic Polymers with Hierarchical Structures and Their Unique Properties.

PubMed

Lu, Tao; Zhu, Shenmin; Ma, Jun; Lin, Jinyou; Wang, Wanlin; Pan, Hui; Tian, Feng; Zhang, Wang; Zhang, Di

2015-10-01

Thermoresponsive photonic materials having hierarchical structures are created by combining a template of Morpho butterfly wings with poly(N-isopropylacrylamide) (PNIPAM) through a chemical bonding and polymerization route. These materials show temperature-induced color tunability. Through reacting with both NIPAM monomers and the amino groups of chitosan in wing scales, glutaraldehyde workes as a bridge by creating chemical bonding between the biotemplate and the PNIPAM. The corresponding reflection peaks red-shift with increase in temperature-an opposite phenomenon to previous studies, demonstrating a thermoresponsive photonic property. This unique phenomenon is caused by the refractive index change due to the volume change of PNIPAM during the temperature rising. This work sets up an efficient strategy for the fabrication of stimuli-responsive photonic materials with hierarchical structures toward extensive applications in science and technology. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sandwiched gold/PNIPAm/gold microstructures for smart plasmonics application: towards the high detection limit and Raman quantitative measurements.

PubMed

Elashnikov, R; Mares, D; Podzimek, T; Švorčík, V; Lyutakov, O

2017-08-07

A smart plasmonic sensor, comprising a layer of a stimuli-responsive polymer sandwiched between two gold layers, is reported. As a stimuli-responsive material, a monolayer of poly(N-isopropylacrylamide) (PNIPAm) crosslinked globules is used. A quasi-periodic structure of the top gold layer facilitates efficient excitation and serves as a support for plasmon excitation and propagation. The intermediate layer of PNIPAm efficiently entraps targeted molecules from solutions. The sensor structure was optimized for efficient light focusing in the "active" PNIPAm layer. The optimization was based on the time-resolved finite-element simulations, which take into account the thickness of gold layers, size of PNIPAm globules and Raman excitation wavelength (780 nm). The prepared structures were characterized using SEM, AFM, UV-Vis refractometry and goniometry. Additional AFM scans were performed in water at two temperatures corresponding to the collapsed and swollen PNIPAm states. The Raman measurements demonstrate a high detection limit and perfect reproducibility of the Raman scattering signal for the prepared sensor. In addition, the use of created SERS structures for the detection of relevant molecules in the medical, biological and safety fields was demonstrated.

The microbial transglutaminase immobilization on carboxylated poly(N-isopropylacrylamide) for thermo-responsivity.

PubMed

Zhou, Jian Qin; He, Ting; Wang, Jian Wen

2016-06-01

Microbial transglutaminase (mTG) is widely utilized in the PEGylation of pharmaceutical proteins. mTG immobilization can be achieved via covalent bonding on solid supports. However, the catalytic efficiency of mTG immobilized on solid supports was significantly reduced by mass transfer limitation. To overcome this limitation, mTG was covalently immobilized on the thermo-responsive carboxylated poly(N-isopropylacrylamide) (pNIPAM). The pNIPAM-mTG conjugate exhibited reversibly solubility in aqueous solution with a low critical solution temperature (LCST) at 39°C, i.e., it was insoluble above 39°C and soluble below 39°C. The pH dependence of the pNIPAM-mTG conjugate was similar with that of the native mTG. Upon conjugation to pNIPAM, the optimal temperature of mTG shifted down from 50-55°C to 40-45°C, and the thermal stability of the conjugate was elevated. The easy separation of the pNIPAM-mTG conjugate with its substrate and the catalytic efficiency of the pNIPAM-mTG conjugate were demonstrated by employing the pNIPAM-mTG conjugate to cross-link bovine serum albumin (BSA) and catalyze PEGylation of therapeutic protein, cytochrome c (Cyt C), respectively. The thermo-responsive mTG is suitable to modify proteins in food processing and biomedical engineering. Copyright © 2016 Elsevier Inc. All rights reserved.

Poly (N-isopropylacrylamide)-functionalized dendrimer as a thermosensitive nanoplatform for delivering malloapelta B against HepG2 cancer cell proliferation

NASA Astrophysics Data System (ADS)

Ngan Le, Phung; Chuong Pham, Dinh; Hai Nguyen, Dai; Quyen Tran, Ngoc; Dimitrov, Vladimir; Ivanov, Petko; Nguyen Xuan, Cuong; Nguyen, Hoai Nam; Khoa Nguyen, Cuu

2017-06-01

In recent years, nanocarriers have emerged as effective platforms for delivering several kinds of herbal medicine and naturally bioactive compounds. In this study we developed an outstanding thermosensitive dendritic nanocarrier to efficiently deliver malloapelta B (Mall B), which is a water insoluble bioactive compound isolated from leaves of Mallotus apelta—Vietnamese medicinal plant. The thermosensitive poly(N-isopropylacrylamide) (PNIPAM) polymer-conjugated polyamidoamine (PAMAM) dendrimer copolymer was prepared via Michael reaction. The copolymer structures were confirmed by proton nuclear magnectic resonance (1H NMR). Morphology of the nanocarrier was observered around 70-120 nm by transmission electron microscopy (TEM). Size distributions were measured by dynamic light scattering (DLS) of the nanocarrier and its Mall B-loaded performed at 146.8 nm and 194.5 nm, respectively. The PNIPAM-g-PAMAM-based nanocarrier exhibited higher Mall B loading efficiency (DL  =  59.93  ±  0.19%) and entrapment efficiency (EE  =  89.98  ±  2.06%) as compared to PNIPAM (DL  =  52.54  ±  0.45% and EE  =  66.45  ±  2.78%). In vitro release indicated that approximately 30% amount of the loaded Mall B released at pH 5.5 after 54 h tracking. At the same time, 12.5% amount of the molecules released at pH 7.4.Cytotoxicity assay results showed that the Mall B-loaded nanocarrier significantly inhibited HepG2 cancer cell proliferation. These obtained results indicated that the nanocarrier could solve hydrophobic property of Mall B for further medicine applications.

Thermoresponsive Polymers for Nuclear Medicine: Which Polymer Is the Best?

PubMed

Sedláček, Ondřej; Černoch, Peter; Kučka, Jan; Konefal, Rafał; Štěpánek, Petr; Vetrík, Miroslav; Lodge, Timothy P; Hrubý, Martin

2016-06-21

Thermoresponsive polymers showing cloud point temperatures (CPT) in aqueous solutions are very promising for the construction of various systems in biomedical field. In many of these applications these polymers get in contact with ionizing radiation, e.g., if they are used as carriers for radiopharmaceuticals or during radiation sterilization. Despite this fact, radiosensitivity of these polymers is largely overlooked to date. In this work, we describe the effect of electron beam ionizing radiation on the physicochemical and phase separation properties of selected thermoresponsive polymers with CPT between room and body temperature. Stability of the polymers to radiation (doses 0-20 kGy) in aqueous solutions increased in the order poly(N-vinylcaprolactam) (PVCL, the least stable) ≪ poly[N-(2,2-difluoroethyl)acrylamide] (DFP) < poly(N-isopropylacrylamide) (PNIPAM) ≪ poly(2-isopropyl-2-oxazoline-co-2-n-butyl-2-oxazoline) (POX). Even low doses of β radiation (1 kGy), which are highly relevant to the storage of polymer radiotherapeutics and sterilization of biomedical systems, cause significant increase in molecular weight due to cross-linking (except for POX, where this effect is weak). In the case of PVCL irradiated with low doses, the increase in molecular weight induced an increase in the CPT of the polymer. For PNIPAM and DFP, there is strong chain hydrophilization leading to an increase in CPT. From this perspective, POX is the most suitable polymer for the construction of delivery systems that experience exposure to radiation, while PVCL is the least suitable and PNIPAM and DFP are suitable only for low radiation demands.

Reversible gelation of rod-like viruses grafted with thermoresponsive polymers.

PubMed

Zhang, Zhenkun; Krishna, Naveen; Lettinga, M Paul; Vermant, Jan; Grelet, Eric

2009-02-17

The synthesis and selected macroscopic properties of a new model system consisting of poly(N-isopropylacrylamide) (PNIPAM)-coated rod-like fd virus particles are presented. The sticky rod-like colloids can be used to study effect of particle shape on gelation transition, the structure and viscoelasticity of isotropic and nematic gels, and to make both open isotropic as well as ordered nematic particle networks. This model system of rod-like colloids, for which the strength of attraction between the particles is tunable, is obtained by chemically grafting highly monodisperse rod-like fd virus particles with thermoresponsive polymers, e.g. PNIPAM. At room temperature, suspensions of the resulting hybrid PNIPAM-fd are fluid sols which are in isotropic or liquid crystalline phases, depending on the particle concentration and ionic strength. During heating/cooling, the suspensions change reversibly between sol and gel state near a critical temperature of approximately 32 degrees C, close to the lower critical solution temperature of free PNIPAM. The so-called nematic gel, which exhibits a cholesteric feature, can therefore be easily obtained. The gelation behavior of PNIPAM-fd system and the structure of the nematic gel have been characterized by rheology, optical microscopy and small-angle X-ray scattering.

A Dual-Responsive Nanocomposite toward Climate-Adaptable Solar Modulation for Energy-Saving Smart Windows.

PubMed

Lee, Heng Yeong; Cai, Yufeng; Bi, Shuguang; Liang, Yen Nan; Song, Yujie; Hu, Xiao Matthew

2017-02-22

In this work, a novel fully autonomous photothermotropic material made by hybridization of the poly(N-isopropylacrylamide) (PNIPAM) hydrogel and antimony-tin oxide (ATO) is presented. In this photothermotropic system, the near-infrared (NIR)-absorbing ATO acts as nanoheater to induce the optical switching of the hydrogel. Such a new passive smart window is characterized by excellent NIR shielding, a photothermally activated switching mechanism, enhanced response speed, and solar modulation ability. Systems with 0, 5, 10, and 15 atom % Sb-doped ATO in PNIPAM were investigated, and it was found that a PNIPAM/ATO nanocomposite is able to be photothermally activated. The 10 atom % Sb-doped PNIPAM/ATO exhibits the best response speed and solar modulation ability. Different film thicknesses and ATO contents will affect the response rate and solar modulation ability. Structural stability tests at 15 cycles under continuous exposure to solar irradiation at 1 sun intensity demonstrated the performance stability of such a photothermotropic system. We conclude that such a novel photothermotropic hybrid can be used as a new generation of autonomous passive smart windows for climate-adaptable solar modulation.

Stimuli-Responsive, Shape-Transforming Nanostructured Particles.

PubMed

Lee, Junhyuk; Ku, Kang Hee; Kim, Mingoo; Shin, Jae Man; Han, Junghun; Park, Chan Ho; Yi, Gi-Ra; Jang, Se Gyu; Kim, Bumjoon J

2017-08-01

Development of particles that change shape in response to external stimuli has been a long-thought goal for producing bioinspired, smart materials. Herein, the temperature-driven transformation of the shape and morphology of polymer particles composed of polystyrene-b-poly(4-vinylpyridine) (PS-b-P4VP) block copolymers (BCPs) and temperature-responsive poly(N-isopropylacrylamide) (PNIPAM) surfactants is reported. PNIPAM acts as a temperature-responsive surfactant with two important roles. First, PNIPAM stabilizes oil-in-water droplets as a P4VP-selective surfactant, creating a nearly neutral interface between the PS and P4VP domains together with cetyltrimethylammonium bromide, a PS-selective surfactant, to form anisotropic PS-b-P4VP particles (i.e., convex lenses and ellipsoids). More importantly, the temperature-directed positioning of PNIPAM depending on its solubility determines the overall particle shape. Ellipsoidal particles are produced above the critical temperature, whereas convex lens-shaped particles are obtained below the critical temperature. Interestingly, given that the temperature at which particle shape change occurs depends solely on the lower critical solution temperature (LCST) of the polymer surfactants, facile tuning of the transition temperature is realized by employing other PNIPAM derivatives with different LCSTs. Furthermore, reversible transformations between different shapes of PS-b-P4VP particles are successfully demonstrated using a solvent-adsorption annealing with chloroform, suggesting great promise of these particles for sensing, smart coating, and drug delivery applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Preventing Small Molecule Nucleation and Crystallization by Sequestering in a Micelle Corona

NASA Astrophysics Data System (ADS)

Li, Ziang; Johnson, Lindsay; Ricarte, Ralm; Yao, Letitia; Hillmyer, Marc; Bates, Frank; Lodge, Timothy

We exploited a blend of hydroxypropyl methylcellulose acetate succinate and poly(N-isopropylacrylamide) (PNIPAm) to improve the solubility and dissolution of a rapidly crystallizing model drug molecule phenytoin and observed synergistic effect in vitro at constant drug loading by varying the blending ratio. Dynamic and static light scattering experiments showed that PNIPAm self-assembled into micelles in aqueous solution. We believe that adding these PNIPAm micelles inhibited both nucleation and crystal growth of phenytoin based on the polarized light micrographs taken from the dissolution media. The drug-polymer intermolecular interaction was revealed by nuclear Overhauser effect spectroscopy and further quantified by diffusion ordered spectroscopy. We found that the phenytoin molecules were sequestered in aqueous solution by partitioning into the corona of the micelle. The blend strategy through the use of self-assembled micelles showcased in this study offers a new platform for designing advanced excipients for oral drug delivery. This study was funded by The Dow Chemical Company through Agreement 224249AT with the University of Minnesota.

Effects of Hofmeister Anions on the LCST of PNIPAM as a Function of Molecular Weight

PubMed Central

Zhang, Yanjie; Furyk, Steven; Sagle, Laura B.; Cho, Younhee; Bergbreiter, David E.; Cremer, Paul S.

2008-01-01

The effect of a series of sodium salts on the lower critical solution temperature (LCST) of poly(N-isopropylacrylamide), PNIPAM, was investigated as a function of molecular weight and polymer concentration with a temperature gradient microfluidic device under a dark-field microscope. In solutions containing sufficient concentrations of kosmotropic anions, the phase transition of PNIPAM was resolved into two separate steps for higher molecular weight samples. The first step of this two step transition was found to be sensitive to the polymer’s molecular weight and solution concentration, while the second step was not. Moreover, the binding of chaotropic anions to the polymer was also influenced by molecular weight. Both sets of results could be explained by the formation of intramolecular and intermolecular hydrogen-bonding between polymer chains. By contrast, the hydrophobic hydration of the isopropyl moieties and polymer backbone was found to be unaffected by either the polymer’s molecular weight or solution concentration. PMID:18820735

Micro- and Nanoscale Hydrogel Systems for Drug Delivery and Tissue Engineering

PubMed Central

Schwall, Christine T.; Banerjee, Ipsita A.

2009-01-01

The pursuit for targeted drug delivery systems has led to the development of highly improved biomaterials with enhanced biocompatibility and biodegradability properties. Micro- and nanoscale components of hydrogels prepared from both natural and artificial components have been gaining significant importance due to their potential uses in cell based therapies, tissue engineering, liquid micro-lenses, cancer therapy, and drug delivery. In this review some of the recent methodologies used in the preparation of a number of synthetic hydrogels such as poly(N-isopropylacrylamide) (pNIPAm), poly(ethylene glycol) (PEG), poly(ethylene oxide) (PEO), polyvinyl alcohol methylacrylate co-polymers (PVA-MA) and polylactic acid (PLA), as well as some of the natural hydrogels and their applications have been discussed in detail.

Facile Fabrication of Composite Membranes with Dual Thermo- and pH-Responsive Characteristics.

PubMed

Ma, Bing; Ju, Xiao-Jie; Luo, Feng; Liu, Yu-Qiong; Wang, Yuan; Liu, Zhuang; Wang, Wei; Xie, Rui; Chu, Liang-Yin

2017-04-26

Facile fabrication of novel functional membranes with excellent dual thermo- and pH-responsive characteristics has been achieved by simply designing dual-layer composite membranes. pH-Responsive poly(styrene)-block-poly(4-vinylpyridine) (PS-b-P4VP) block copolymers and polystyrene blended with thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) nanogels are respectively used to construct the top layer and bottom layer of composite membranes. The stretching/coiling conformation changes of the P4VP chains around the pK a (∼3.5-4.5) provide the composite membranes with extraordinary pH-responsive characteristics, and the volume phase transitions of PNIPAM nanogels at the pore/matrix interfaces in the bottom layer around the volume phase transition temperature (VPTT, ∼33 °C) provide the composite membranes with great thermoresponsive characteristics. The microstructures, permeability performances, and dual stimuli-responsive characteristics can be well tuned by adjusting the content of PNIPAM nanogels and the thickness of the PS-b-P4VP top layer. The water fluxes of the composite membranes can be changed in order of magnitude by changing the environment temperature and pH, and the dual thermo- and pH-responsive permeation performances of the composite membranes are satisfactorily reversible and reproducible. The membrane fabrication strategy in this work provides valuable guidance for further development of dual stimuli-responsive membranes or even multi stimuli-responsive membranes.

Phase behavior of binary and polydisperse suspensions of compressible microgels controlled by selective particle deswelling

NASA Astrophysics Data System (ADS)

Scotti, A.; Gasser, U.; Herman, E. S.; Han, Jun; Menzel, A.; Lyon, L. A.; Fernandez-Nieves, A.

2017-09-01

We investigate the phase behavior of suspensions of poly(N -isopropylacrylamide) (pNIPAM) microgels with either bimodal or polydisperse size distribution. We observe a shift of the fluid-crystal transition to higher concentrations depending on the polydispersity or the fraction of large particles in suspension. Crystallization is observed up to polydispersities as high as 18.5%, and up to a number fraction of large particles of 29% in bidisperse suspensions. The crystal structure is random hexagonal close-packed as in monodisperse pNIPAM microgel suspensions. We explain our experimental results by considering the effect of bound counterions. Above a critical particle concentration, these cause deswelling of the largest microgels, which are the softest, changing the size distribution of the suspension and enabling crystal formation in conditions where incompressible particles would not crystallize.

Organic-dye-coupled magnetic nanoparticles encaged inside thermoresponsive PNIPAM Microcapsules.

PubMed

Guo, Jia; Yang, Wuli; Deng, Yonghui; Wang, Changchun; Fu, Shoukuan

2005-07-01

We present a new approach for the fabrication of thermoresponsive polymer microcapsules with mobile magnetic cores that undergo a volume phase-transition upon changing the temperature and are collected under an external magnetic field. We have prepared organic/inorganic composite microspheres with a well-defined core-shell structure that are composed of a crosslinked poly(N-isopropylacrylamide) (PNIPAM) shell and silica cores dotted centrally by magnetite nanoparticles. Since the infiltration of template-decomposed products is dependent on the permeability of PNIPAM shells triggered by changes of exterior temperature, the silica layer sandwiched between the magnetic core and the PNIPAM shell was quantitatively removed to generate PNIPAM microcapsules with mobile magnetic cores by treatment with aqueous NaOH solution. For development of the desired multifunctional microcapsules, modification of the unetched silica surface interiors can be realized by treatment with a silane coupling agent containing functional groups that can easily bind to catalysts, enzymes, or labeling molecules. Herein, fluorescein isothiocyanate (FITC), which is a common organic dye, is attached to the insides of the mobile magnetic cores to give PNIPAM microcapsules with FITC-labeled magnetic cores. In this system, it can be expected that an extension of the functionalization of the cavity properties of smart polymer microcapsules is to immobilize other target molecules onto the mobile cores in order to introduce other desired functions in the hollow cage.

Synthesis and characterization of GO-hydrogels composites

NASA Astrophysics Data System (ADS)

Pereyra, J. Y.; Cuello, E. A.; Coneo Rodriguez, R.; Barbero, C. A.; Yslas, E. I.; Salavagione, H. J.; Acevedo, D. F.

2017-10-01

The preparation of poly(N-isopropylacrylamide) (PNIPAm) hydrogel nanocomposites containing graphene oxide (GO) and GO plus carbon nanotubes (CNT) in the polymer network is communicated. This one-pot preparation methods include the dispersion of GO (or GO plus CNT) in a solution of monomers and the subsequent polymerization. The texture of the nanocomposites was studied using scanning electron microscopy (SEM), where very compact surfaces are observed suggesting good dispersion of GO sheets and CNTs within the polymer matrix. The presence of GO inside the polymer network diminished the equilibrium swelling values and increased the elastic modulus up to 162 % with respect to the pure gel. Similar results were observed for the composite with CNT. Furthermore, the electrical resistivity of PNIPAm-GO diminishes as the applied compression force increases, being 50 % lower than hydrogel without GO. Moreover, the electrochemical properties of the hydrogels, evaluated by cyclic voltammetry, indicate highly reversible electrical charge/discharge response. In order to apply these materials for antibiotic delivery, the absorption of tetracycline (tet) is evaluated and the nanocomposites showed better absorption capability and improved antibiotic delivery. Preliminary results suggest that tet loaded PNIPAm-GO and PNIPAM-GO-CNT display antimicrobial activity against the Pseudomonas aeruginosa turning these materials as potential candidates for biomedical applications.

Thermo-responsive polymeric nanoparticles for enhancing neuronal differentiation of human induced pluripotent stem cells.

PubMed

Seo, Hye In; Cho, Ann-Na; Jang, Jiho; Kim, Dong-Wook; Cho, Seung-Woo; Chung, Bong Geun

2015-10-01

We report thermo-responsive retinoic acid (RA)-loaded poly(N-isopropylacrylamide)-co-acrylamide (PNIPAM-co-Am) nanoparticles for directing human induced pluripotent stem cell (hiPSC) fate. Fourier transform infrared spectroscopy and (1)H nuclear magnetic resonance analysis confirmed that RA was efficiently incorporated into PNIAPM-co-Am nanoparticles (PCANs). The size of PCANs dropped with increasing temperatures (300-400 nm at room temperature, 80-90 nm at 37°C) due to its phase transition from hydrophilic to hydrophobic. Due to particle shrinkage caused by this thermo-responsive property of PCANs, RA could be released from nanoparticles in the cells upon cellular uptake. Immunocytochemistry and quantitative real-time polymerase chain reaction analysis demonstrated that neuronal differentiation of hiPSC-derived neuronal precursors was enhanced after treatment with 1-2 μg/ml RA-loaded PCANs. Therefore, we propose that this PCAN could be a potentially powerful carrier for effective RA delivery to direct hiPSC fate to neuronal lineage. The use of induced pluripotent stem cells (iPSCs) has been at the forefront of research in the field of regenerative medicine, as these cells have the potential to differentiate into various terminal cell types. In this article, the authors utilized a thermo-responsive polymer, Poly(N-isopropylacrylamide) (PNIPAM), as a delivery platform for retinoic acid. It was shown that neuronal differentiation could be enhanced in hiPSC-derived neuronal precursor cells. This method may pave a way for future treatment of neuronal diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Rolling and aging in temperature-ramp soft adhesion

NASA Astrophysics Data System (ADS)

Boniello, Giuseppe; Tribet, Christophe; Marie, Emmanuelle; Croquette, Vincent; Zanchi, Dražen

2018-01-01

Immediately before adsorption to a horizontal substrate, sinking polymer-coated colloids can undergo a complex sequence of landing, jumping, crawling, and rolling events. Using video tracking, we studied the soft adhesion to a horizontal flat plate of micron-size colloids coated by a controlled molar fraction f of the poly(lysine)-grafted-poly(N-isopropylacrylamide) (PLL-g-PNIPAM) which is a temperature-sensitive polymer. We ramp the temperature from below to above Tc=32 ±1∘C , at which the PNIPAM polymer undergoes a transition, triggering attractive interaction between microparticles and surface. The adsorption rate, the effective in-plane (x -y ) diffusion constant, and the average residence time distribution over z were extracted from the Brownian motion records during last seconds before immobilization. Experimental data are understood within a rate-equations-based model that includes aging effects and includes three populations: the untethered, the rolling, and the arrested colloids. We show that preadsorption dynamics casts a characteristic scaling function α (f ) proportional to the number of available PNIPAM patches met by soft contact during Brownian rolling. In particular, the increase of in-plane diffusivity with increasing f is understood: The stickiest particles have the shortest rolling regime prior to arrest, so that their motion is dominated by the untethered phase.

Microgel-Encapsulated Methylene Blue for the Treatment of Breast Cancer Cells by Photodynamic Therapy

PubMed Central

Khanal, Anil; Bui, Minh-Phuong Ngoc

2014-01-01

Purpose Photodynamic therapy (PDT) is gaining increasing recognition for breast cancer treatment because it offers local selectivity and reduced toxic side effects compared to radiotherapy and chemotherapy. In PDT, photosensitizer drugs are loaded in different nanomaterials and used in combination with light exposure. However, the most representative issue with PDT is the difficulty of nanomaterials to encapsulate anticancer drugs at high doses, which results in low efficacy of the PDT treatment. Here, we proposed the development of the poly(N-isopropylacrylamide) (PNIPAM) microgel for the encapsulation of methylene blue, an anticancer drug, for its use as breast cancer treatment in MCF-7 cell line. Methods We developed biocompatible microgels based on nonfunctionalized PNIPAM and its corresponding anionically functionalized PNIPAM and polyacrylic acid (PNIPAM-co-PAA) microgel. Methylene blue was used as the photosensitizer drug because of its ability to generate toxic reactive oxygen species upon exposure to light at 664 nm. Core PNIPAM and core/shell PNIPAM-co-PAA microgels were synthesized and characterized using ultraviolet-visible spectroscopy and dynamic light scattering. The effect of methylene blue was evaluated using the MCF-7 cell line. Results Loading of methylene blue in core PNIPAM microgel was higher than that in the core/shell PNIPAM-co-PAA microgel, indicating that electrostatic interactions did not play an important role in loading a cationic drug. This behavior is probably due to the skin layer inhibiting the high uptake of drugs in the PNIPAM-co-PAA microgel. Core PNIPAM microgel effectively retained the cationic drug (i.e., methylene blue) for several hours compared to core/shell PNIPAM-co-PAA and enhanced its photodynamic efficacy in vitro more than that of free methylene blue. Conclusion Our results showed that the employment of core PNIPAM and core/shell PNIPAM-co-PAA microgels enhanced the encapsulation of methylene blue. Core PNIPAM microgel released the drug more slowly than did core/shell PNIPAM-co-PAA, and it effectively inhibited the growth of MCF-7 cells. PMID:24744793

Microgel-encapsulated methylene blue for the treatment of breast cancer cells by photodynamic therapy.

PubMed

Khanal, Anil; Bui, Minh-Phuong Ngoc; Seo, Seong S

2014-03-01

Photodynamic therapy (PDT) is gaining increasing recognition for breast cancer treatment because it offers local selectivity and reduced toxic side effects compared to radiotherapy and chemotherapy. In PDT, photosensitizer drugs are loaded in different nanomaterials and used in combination with light exposure. However, the most representative issue with PDT is the difficulty of nanomaterials to encapsulate anticancer drugs at high doses, which results in low efficacy of the PDT treatment. Here, we proposed the development of the poly(N-isopropylacrylamide) (PNIPAM) microgel for the encapsulation of methylene blue, an anticancer drug, for its use as breast cancer treatment in MCF-7 cell line. We developed biocompatible microgels based on nonfunctionalized PNIPAM and its corresponding anionically functionalized PNIPAM and polyacrylic acid (PNIPAM-co-PAA) microgel. Methylene blue was used as the photosensitizer drug because of its ability to generate toxic reactive oxygen species upon exposure to light at 664 nm. Core PNIPAM and core/shell PNIPAM-co-PAA microgels were synthesized and characterized using ultraviolet-visible spectroscopy and dynamic light scattering. The effect of methylene blue was evaluated using the MCF-7 cell line. Loading of methylene blue in core PNIPAM microgel was higher than that in the core/shell PNIPAM-co-PAA microgel, indicating that electrostatic interactions did not play an important role in loading a cationic drug. This behavior is probably due to the skin layer inhibiting the high uptake of drugs in the PNIPAM-co-PAA microgel. Core PNIPAM microgel effectively retained the cationic drug (i.e., methylene blue) for several hours compared to core/shell PNIPAM-co-PAA and enhanced its photodynamic efficacy in vitro more than that of free methylene blue. Our results showed that the employment of core PNIPAM and core/shell PNIPAM-co-PAA microgels enhanced the encapsulation of methylene blue. Core PNIPAM microgel released the drug more slowly than did core/shell PNIPAM-co-PAA, and it effectively inhibited the growth of MCF-7 cells.

Poly-N-Isopropylacrylamide/acrylic Acid Copolymers for the Generation of Nanostructures at Mica Surfaces and as Hydrophobic Host Systems for the Porin MspA from Mycobacterium smegmatis.

PubMed

Gamage, Pubudu; Basel, Matthew T; Lovell, Kimberly; Pokhrel, Megh Raj; Battle, Deletria; Ito, Takashi; Pavlenok, Mikhail; Niederweis, Michael; Bossmann, Stefan H

2009-09-17

The work presented here aims at utilizing poly-N-isopropyl-acrylamide/acrylic acid copolymers to create nanostructured layers on mica surfaces by a simple spin-casting procedure. The average composition of the copolymers determined by elemental analysis correlates excellently with the feed composition indicating that the radical polymerization process is statistical. The resulting surfaces were characterized by Atomic Force Microscopy (magnetic AC-mode) at the copolymer/air interface. Postpolymerization modification of the acrylic acid functions with perfluoro-octyl-iodide decreased the tendency towards spontaneous formation of nanopores. Crosslinking of individual polymer chains permitted the generation of ultraflat layers, which hosted the mycobacterial channel protein MspA, without compromising its channel function. The comparison of copolymers of very similar chemical composition that have been prepared by living radical polymerization and classic radical polymerization indicated that differences in polydispersity played only a minor role when poly-N-isopropyl-acrylamide/acrylic acid copolymers were spincast, but a major role when copolymers featuring the strongly hydrophobic perfluoro-octyl-labels were used. The mean pore diameters were 23.8+/-4.4 nm for P[(NIPAM)(95.5)-co-(AA)(4.5)] (PDI (polydispersity index)=1.55) and 21.8+/-4.2 nm for P[(NIPAM)(95.3)-co-(AA)(4.7)] (PDI=1.25). The depth of the nanopores was approx. 4 nm. When depositing P[(NIPAM)(95)-co-(AA)(2.8)-AAC(8)F(17 2.2)] (PDI=1.29) on Mica, the resulting mean pore diameter was 35.8+/-7.1 nm, with a depth of only 2 nm.

Poly-N-Isopropylacrylamide/acrylic Acid Copolymers for the Generation of Nanostructures at Mica Surfaces and as Hydrophobic Host Systems for the Porin MspA from Mycobacterium smegmatis

PubMed Central

Gamage, Pubudu; Basel, Matthew T.; Lovell, Kimberly; Pokhrel, Megh Raj; Battle, Deletria; Ito, Takashi; Pavlenok, Mikhail; Niederweis, Michael

2009-01-01

The work presented here aims at utilizing poly-N-isopropyl-acrylamide/acrylic acid copolymers to create nanostructured layers on mica surfaces by a simple spin-casting procedure. The average composition of the copolymers determined by elemental analysis correlates excellently with the feed composition indicating that the radical polymerization process is statistical. The resulting surfaces were characterized by Atomic Force Microscopy (magnetic AC-mode) at the copolymer/air interface. Postpolymerization modification of the acrylic acid functions with perfluoro-octyl-iodide decreased the tendency towards spontaneous formation of nanopores. Crosslinking of individual polymer chains permitted the generation of ultraflat layers, which hosted the mycobacterial channel protein MspA, without compromising its channel function. The comparison of copolymers of very similar chemical composition that have been prepared by living radical polymerization and classic radical polymerization indicated that differences in polydispersity played only a minor role when poly-N-isopropyl-acrylamide/acrylic acid copolymers were spincast, but a major role when copolymers featuring the strongly hydrophobic perfluoro-octyl-labels were used. The mean pore diameters were 23.8±4.4 nm for P[(NIPAM)95.5-co-(AA)4.5] (PDI (polydispersity index)=1.55) and 21.8±4.2 nm for P[(NIPAM)95.3-co-(AA)4.7] (PDI=1.25). The depth of the nanopores was approx. 4 nm. When depositing P[(NIPAM)95-co-(AA)2.8-AAC8F17 2.2] (PDI=1.29) on Mica, the resulting mean pore diameter was 35.8±7.1 nm, with a depth of only 2 nm. PMID:20161351

Thermoresponsive core-shell magnetic nanoparticles for combined modalities of cancer therapy.

PubMed

Purushotham, S; Chang, P E J; Rumpel, H; Kee, I H C; Ng, R T H; Chow, P K H; Tan, C K; Ramanujan, R V

2009-07-29

Thermoresponsive polymer-coated magnetic nanoparticles loaded with anti-cancer drugs are of considerable interest for novel multi-modal cancer therapies. Such nanoparticles can be used for magnetic drug targeting followed by simultaneous hyperthermia and drug release. Gamma-Fe(2)O(3) iron oxide magnetic nanoparticles (MNP) with average sizes of 14, 19 and 43 nm were synthesized by high temperature decomposition. Composite magnetic nanoparticles (CNP) of 43 nm MNP coated with the thermoresponsive polymer poly-n-isopropylacrylamide (PNIPAM) were prepared by dispersion polymerization of n-isopropylacrylamide monomer in the presence of the MNP. In vitro drug release of doxorubicin-(dox) loaded dehydrated CNP at temperatures below and above the lower critical solution temperature of PNIPAM (34 degrees C) revealed a weak dependence of drug release on swelling behavior. The particles displayed Fickian diffusion release kinetics; the maximum dox release at 42 degrees C after 101 h was 41%. In vitro simultaneous hyperthermia and drug release of therapeutically relevant quantities of dox was achieved, 14.7% of loaded dox was released in 47 min at hyperthermia temperatures. In vivo magnetic targeting of dox-loaded CNP to hepatocellular carcinoma (HCC) in a buffalo rat model was studied by magnetic resonance imaging (MRI) and histology. In summary, the good in vitro and in vivo performance of the doxorubicin-loaded thermoresponsive polymer-coated magnetic nanoparticles suggests considerable promise for applications in multi-modal treatment of cancer.

Adhesion switch on a gecko-foot inspired smart nanocupule surface

NASA Astrophysics Data System (ADS)

Song, Wenlong

2014-10-01

A gecko-foot inspired nanocupule surface prepared by an AAO template covering method was composed of poly(N-isopropylacrylamide) and polystyrene blend. Both superhydrophobicity and high adhesion force were exhibited on the PNIPAm/PS film at room temperature. Moreover, by controlling the temperature, the wettability of the film could be switched between 138.1 +/- 5.5° and 150.6 +/- 1.5°, and the adhesion force could also be correspondingly tuned accurately by temperature. This reversibility in both wettability and adhesion force could be used to construct smart devices for fine selection of water droplets. The proof-of-concept was demonstrated by the selective catching of precise weight controlled water droplets at different temperatures. This work could help us to design new type of devices for blood bioanalysis or lossless drug transportation.A gecko-foot inspired nanocupule surface prepared by an AAO template covering method was composed of poly(N-isopropylacrylamide) and polystyrene blend. Both superhydrophobicity and high adhesion force were exhibited on the PNIPAm/PS film at room temperature. Moreover, by controlling the temperature, the wettability of the film could be switched between 138.1 +/- 5.5° and 150.6 +/- 1.5°, and the adhesion force could also be correspondingly tuned accurately by temperature. This reversibility in both wettability and adhesion force could be used to construct smart devices for fine selection of water droplets. The proof-of-concept was demonstrated by the selective catching of precise weight controlled water droplets at different temperatures. This work could help us to design new type of devices for blood bioanalysis or lossless drug transportation. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr04090b

Thermoresponsive PNIPAM Coatings on Nanostructured Gratings for Cell Alignment and Release

DOE PAGES

Zhernenkov, Mikhail; Ashkar, Rana; Feng, Hao; ...

2015-05-20

Thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) has been widely used as a surface coating to thermally control the detachment of adsorbed cells without the need for extreme stimuli such as enzyme treatment. Recently, the use of 2D and 3D scaffolds in controlling cell positioning, growth, spreading, and migration has been of a great interest in tissue engineering and cell biology. We use a PNIPAM polymer surface coating atop a nanostructured linear diffraction grating to controllably change the surface topography of 2D linear structures using temperature stimuli. Neutron reflectometry and surface diffraction are utilized to examine the conformity of the polymer coating to themore » grating surface, its hydration profile, and its evolution in response to temperature variations. Our results show that, in the collapsed state, the PNIPAM coating conforms to the grating structures and retains a uniform hydration of 63%. In the swollen state, the polymer expands beyond the grating channels and absorbs up to 87% water. Such properties are particularly desirable for 2D cell growth scaffolds with a built-in nonextreme tissue-release mechanism. Indeed, the current system demonstrates advanced performance in the effective alignment of cultured fibroblast cells and the easy release of the cells upon temperature change.« less

Thermoresponsive PNIPAM Coatings on Nanostructured Gratings for Cell Alignment and Release

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

Zhernenkov, Mikhail; Ashkar, Rana; Feng, Hao

Thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) has been widely used as a surface coating to thermally control the detachment of adsorbed cells without the need for extreme stimuli such as enzyme treatment. Recently, the use of 2D and 3D scaffolds in controlling cell positioning, growth, spreading, and migration has been of a great interest in tissue engineering and cell biology. We use a PNIPAM polymer surface coating atop a nanostructured linear diffraction grating to controllably change the surface topography of 2D linear structures using temperature stimuli. Neutron reflectometry and surface diffraction are utilized to examine the conformity of the polymer coating to themore » grating surface, its hydration profile, and its evolution in response to temperature variations. Our results show that, in the collapsed state, the PNIPAM coating conforms to the grating structures and retains a uniform hydration of 63%. In the swollen state, the polymer expands beyond the grating channels and absorbs up to 87% water. Such properties are particularly desirable for 2D cell growth scaffolds with a built-in nonextreme tissue-release mechanism. Indeed, the current system demonstrates advanced performance in the effective alignment of cultured fibroblast cells and the easy release of the cells upon temperature change.« less

Poly(N-isopropylacrylamide)-coated thermo-responsive nanoparticles for controlled delivery of sulfonated Zn-phthalocyanine in Chinese hamster ovary cells in vitro and zebra fish in vivo

NASA Astrophysics Data System (ADS)

He, Jia; Chen, Ji-Yao; Wang, Pu; Wang, Pei-Nan; Guo, Jia; Yang, Wu-Li; Wang, Chang-Chun; Peng, Qian

2007-10-01

Poly(N-isopropylacrylamide) (PNIPAM)-coated Fe3O4@SiO2@CdTe multifunctional nanoparticles with photoluminescent (PL), thermosensitive and magnetic properties, were investigated as carriers to deliver water-soluble, fluorescent sulfonated Zn-phthalocyanine (ZnPcS), a photosensitizing drug for photodynamic therapy of cancer, in Chinese hamster ovary (CHO) cells in vitro and zebra fish in vivo. PNIPAM is a well-known thermo-responsive polymer with a volume phase transition temperature. This property allows it to be swollen in water at temperatures lower than 32-34 °C to take up ZnPcS and shrunken to expel the drug at higher temperatures. Since the PL band of CdTe quantum dots (QDs) as indicators for the nanoparticles is at 585 nm and the emission band of ZnPcS is at 680 nm, it is possible to study the temperature-dependent release of ZnPcS from the nanoparticles by fluorescence measurements. ZnPcS was embedded in the PNIPAM of the nanoparticles at 25 °C in phosphate buffered saline (PBS) solution and released at 37 °C, measured with a spectrophotometer. When CHO cells had been incubated with the ZnPcS-loaded nanoparticles at 27 °C, a similar intracellular localization pattern of CdTe QDs and ZnPcS was seen by multichannel measurements in confocal laser scanning microscopy (CLSM), but a diffuse pattern of only ZnPcS fluorescence was detected in the cytoplasm of the cells at 37 °C, indicating a release of ZnPcS from the nanoparticles. Similar results were also found in the intestinal tract of zebra fish in vivo after intake of the nanoparticles. Since the nanoparticles contain magnetic (Fe3O4) material, the nanoparticles could also be manipulated to change their location in the intestinal tract of the zebra fish with an external magnetic field gradient of 300 G mm-1. The results presented suggest that such multifunctional nanoparticles may have combined potential for temperature-dependent drug delivery, QD photodetection and magnetic manipulation in diagnosis and therapy of diseases.

Thermally-induced softening of PNIPAm-based nanopillar arrays.

PubMed

Sanz, Belén; von Bilderling, Catalina; Tuninetti, Jimena S; Pietrasanta, Lía; Mijangos, Carmen; Longo, Gabriel S; Azzaroni, Omar; Giussi, Juan M

2017-03-29

The surface properties of soft nanostructured hydrogels are crucial in the design of responsive materials that can be used as platforms to create adaptive devices. The lower critical solution temperature (LCST) of thermo-responsive hydrogels such as poly(N-isopropylacrylamide) (PNIPAm) can be modified by introducing a hydrophilic monomer to create a wide range of thermo-responsive micro-/nano-structures in a large temperature range. Using surface initiation atom-transfer radical polymerization in synthesized anodized aluminum oxide templates, we designed, fabricated, and characterized thermo-responsive nanopillars based on PNIPAm hydrogels with tunable mechanical properties by incorporating acrylamide monomers (AAm). In addition to their LCST, the incorporation of a hydrophilic entity in the nanopillars based on PNIPAm has abruptly changed the topological and mechanical properties of our system. To gain an insight into the mechanical properties of the nanostructure, its hydrophilic/hydrophobic behavior and topological characteristics, atomic force microscopy, molecular dynamics simulations and water contact angle studies were combined. When changing the nanopillar composition, a significant and opposite variation was observed in their mechanical properties. As temperature increased above the LCST, the stiffness of PNIPAm nanopillars, as expected, did so too, in contrast to the stiffness of PNIPAm-AAm nanopillars that decreased significantly. The molecular dynamics simulations proposed a local molecular rearrangement in our nanosystems at the LCST. The local aggregation of NIPAm segments near the center of the nanopillars displaced the hydrophilic AAm units towards the surface of the structure leading to contact with the aqueous environment. This behavior was confirmed via contact angle measurements below and above the LCST.

Responsive etalon based on PNIPAM@SiO2 composite spacer with rapid response rate and excellent repeatability for sensing application

NASA Astrophysics Data System (ADS)

Wang, Tieqiang; Wang, Shuli; Zhang, Xun; Song, Guoshuai; Yu, Ye; Chen, Xinyang; Fu, Yu; Zhang, Junhu; Yang, Bai

2015-07-01

In this paper, we demonstrate a responsive etalon fabricated through combining colloidal lithography and surface-initiated atom-transfer radical polymerization (SI-ATRP). The responsive etalon is simply constructed with one responsive spacer sandwiched by two reflective layers, and the middle responsive spacer is constructed by grafting thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) brushes on a SiO2 nanosphere array. The etalon possesses one single interference peak in the visible region, and the interference peak changes sensitively against the concentration of the external stimulant (water vapor) or the temperature of the system, owing to the responsiveness of the PNIPAM brush. Importantly, the as-prepared etalon shows a rapid response rate and excellent stability, and it is also handy to realize the miniaturization and integration of the responsive etalon based on a conventional micro-fabrication method. These features all make the as-prepared responsive etalon an attractive candidate for future sensing applications. We believe such responsive etalons are promising for the fabrication of smart photonic materials and optical sensors that may be useful in tissue engineering, medical diagnosis, public security, and biochip areas.

Functional bone-mimetic scaffolds of bicontinuous, thermo-responsive L 3-phase silica/hydroxyapatite nanocomposites

NASA Astrophysics Data System (ADS)

Chang, Jeong Ho; Kim, Kyung Ja

2007-12-01

This work presents the highly controlled drug delivery system free from the burst release at an initial stage and equipped with the capability of long term drug release. The nanoporous drug releasing reservoir was combined with porous body resembling cancellous bone. The materials were prepared by the integration of synthesized inorganic hydroxyapatite (HA) and the hybrid gels of bicontinuous sponge-phased L3 silicate and thermo-responsive poly(N-isopropylacrylamide) (L3-PNIPAm gels). The materials were designed to have the three dimensionally interconnected heterogeneous porosity of macro- and mesoporosity, in which the HA has the macroporosity of 150μm to be impregnated the drug into the pores and the L3-PNIPAm gels have mesoporosity of 5 nm to regulate the temperature sensitive drug-release through the pore channels and polymeric network, respectively. Consequently, this bone-mimetic system gave the highly long term drug release over the 60 days without the burst release. The release rate could be controlled with the change of the HA and PNIPAm composition ratios. The structural characterization was achieved by TEM, SEM, XRD, Micro-Raman spectroscopy, BET, and the direct contact cytotoxicity test was also described.

pH- and Temperature-Sensitive Hydrogel Nanoparticles with Dual Photoluminescence for Bioprobes.

PubMed

Zhao, Yue; Shi, Ce; Yang, Xudong; Shen, Bowen; Sun, Yuanqing; Chen, Yang; Xu, Xiaowei; Sun, Hongchen; Yu, Kui; Yang, Bai; Lin, Quan

2016-06-28

This study demonstrates high contrast and sensitivity by designing a dual-emissive hydrogel particle system, whose two emissions respond to pH and temperature strongly and independently. It describes the photoluminescence (PL) response of poly(N-isopropylacrylamide) (PNIPAM)-based core/shell hydrogel nanoparticles with dual emission, which is obtained by emulsion polymerization with potassium persulfate, consisting of the thermo- and pH-responsive copolymers of PNIPAM and poly(acrylic acid) (PAA). A red-emission rare-earth complex and a blue-emission quaternary ammonium tetraphenylethylene derivative (d-TPE) with similar excitation wavelengths are inserted into the core and shell of the hydrogel nanoparticles, respectively. The PL intensities of the nanoparticles exhibit a linear temperature response in the range from 10 to 80 °C with a change as large as a factor of 5. In addition, the blue emission from the shell exhibits a linear pH response between pH 6.5 and 7.6 with a resolution of 0.1 unit, while the red emission from the core is pH-independent. These stimuli-responsive PL nanoparticles have potential applications in biology and chemistry, including bio- and chemosensors, biological imaging, cancer diagnosis, and externally activated release of anticancer drugs.

Nature-inspired multifunctional membrane fabricated by adaptive hybridization of PNIPAm and PPy

NASA Astrophysics Data System (ADS)

Kim, Hyejeong; Kim, Kiwoong; Lee, Sang Joon

2017-11-01

Specialized plant organs, such as guard cells of stomata, consist of soft materials with deformability and electrochemical properties in response to various environmental stimuli. Stimulus-responsive hydrogels with electrochemical properties are good candidates for imitating such functionalities having great potential in a wide range of applications. However, conductive hydrogels are usually mechanically rigid and the fabrication technology of structured hydrogels has low reproducibility. Here, inspired by stimulus-responsive functionalities of plants, a thermo-responsive multifunctional hybrid membrane (HM) is synthesized through the in situ hybridization of conductive poly(pyrrole)(PPy) on a photopolymerized poly(N-isopropylacrylamide)(PNIPAm) membrane. The various properties of the HM are investigated to characterize its multiple functions. In terms of morphology, the HM can be easily fabricated into various structures, and exhibits thermo-responsive deformability. In terms of functionality, it exhibits various electrical and charge responses to thermal stimuli. This simple and efficient fabrication method can be used as a promising platform for fabricating a variety of functional devices, such as actuators, biosensors, and filtration membranes. This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean government (MSIP) (No. 2017R1A2B3005415).

Patchy micelles based on coassembly of block copolymer chains and block copolymer brushes on silica particles.

PubMed

Zhu, Shuzhe; Li, Zhan-Wei; Zhao, Hanying

2015-04-14

Patchy particles are a type of colloidal particles with one or more well-defined patches on the surfaces. The patchy particles with multiple compositions and functionalities have found wide applications from the fundamental studies to practical uses. In this research patchy micelles with thiol groups in the patches were prepared based on coassembly of free block copolymer chains and block copolymer brushes on silica particles. Thiol-terminated and cyanoisopropyl-capped polystyrene-block-poly(N-isopropylacrylamide) block copolymers (PS-b-PNIPAM-SH and PS-b-PNIPAM-CIP) were synthesized by reversible addition-fragmentation chain transfer polymerization and chemical modifications. Pyridyl disulfide-functionalized silica particles (SiO2-SS-Py) were prepared by four-step surface chemical reactions. PS-b-PNIPAM brushes on silica particles were prepared by thiol-disulfide exchange reaction between PS-b-PNIPAM-SH and SiO2-SS-Py. Surface micelles on silica particles were prepared by coassembly of PS-b-PNIPAM-CIP and block copolymer brushes. Upon cleavage of the surface micelles from silica particles, patchy micelles with thiol groups in the patches were obtained. Dynamic light scattering, transmission electron microscopy, and zeta-potential measurements demonstrate the preparation of patchy micelles. Gold nanoparticles can be anchored onto the patchy micelles through S-Au bonds, and asymmetric hybrid structures are formed. The thiol groups can be oxidized to disulfides, which results in directional assembly of the patchy micelles. The self-assembly behavior of the patchy micelles was studied experimentally and by computer simulation.

Tunable Electromagnetic Coupling in Plasmonic Nanostructures Mediated by Thermoresponsive Polymer Brushes.

PubMed

Nguyen, Mai; Kanaev, Andrei; Sun, Xiaonan; Lacaze, Emmanuelle; Lau-Truong, Stéphanie; Lamouri, Aazdine; Aubard, Jean; Felidj, Nordin; Mangeney, Claire

2015-11-24

A smart and highly SERS-active plasmonic platform was designed by coupling regular arrays of nanotriangles to colloidal gold nanorods via a thermoresponsive polymer spacer (poly(N-isopropylacrylamide), PNIPAM). The substrates were prepared by combining a top-down and a bottom-up approach based on nanosphere lithography, surface-initiated controlled radical polymerization, and colloidal assembly. This multistep strategy provided regular hexagonal arrays of nanotriangles functionalized by polymer brushes and colloidal gold nanorods, confined exclusively on the nanotriangle surface. Interestingly, one could finely tune the gold nanorod impregnation on the polymer-coated nanostructures by adjusting the polymer layer thickness, leading to highly coupled plasmonic systems for intense SERS signal. Moreover, the thermoresponsive properties of the PNIPAM brushes could be wisely handled in order to monitor the SERS activity of the nanostructures coupled via this polymer spacer. The coupled hybrid plasmonic nanostructures designed in this work are therefore very promising smart platforms for the sensitive detection of analytes by SERS.

Polymersomes prepared from thermoresponsive fluorescent protein-polymer bioconjugates: capture of and report on drug and protein payloads.

PubMed

Wong, Chin Ken; Laos, Alistair J; Soeriyadi, Alexander H; Wiedenmann, Jörg; Curmi, Paul M G; Gooding, J Justin; Marquis, Christopher P; Stenzel, Martina H; Thordarson, Pall

2015-04-27

Polymersomes provide a good platform for targeted drug delivery and the creation of complex (bio)catalytically active systems for research in synthetic biology. To realize these applications requires both spatial control over the encapsulation components in these polymersomes and a means to report where the components are in the polymersomes. To address these twin challenges, we synthesized the protein-polymer bioconjugate PNIPAM-b-amilFP497 composed of thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) and a green-fluorescent protein variant (amilFP497). Above 37 °C, this bioconjugate forms polymersomes that can (co-)encapsulate the fluorescent drug doxorubicin and the fluorescent light-harvesting protein phycoerythrin 545 (PE545). Using fluorescence lifetime imaging microscopy and Förster resonance energy transfer (FLIM-FRET), we can distinguish the co-encapsulated PE545 protein inside the polymersome membrane while doxorubicin is found both in the polymersome core and membrane. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of amphiphilic tadpole-shaped linear-cyclic diblock copolymers via ring-opening polymerization directly initiating from cyclic precursors and their application as drug nanocarriers.

PubMed

Wan, Xuejuan; Liu, Tao; Liu, Shiyong

2011-04-11

We report on the facile synthesis of well-defined amphiphilic and thermoresponsive tadpole-shaped linear-cyclic diblock copolymers via ring-opening polymerization (ROP) directly initiating from cyclic precursors, their self-assembling behavior in aqueous solution, and the application of micellar assemblies as controlled release drug nanocarriers. Starting from a trifunctional core molecule containing alkynyl, hydroxyl, and bromine moieties, alkynyl-(OH)-Br, macrocyclic poly(N-isopropylacrylamide) (c-PNIPAM) bearing a single hydroxyl functionality was prepared by atom transfer radical polymerization (ATRP), the subsequent end group transformation into azide functionality, and finally the intramacromolecular ring closure reaction via click chemistry. The target amphiphilic tadpole-shaped linear-cyclic diblock copolymer, (c-PNIPAM)-b-PCL, was then synthesized via the ROP of ε-caprolactone (CL) by directly initiating from the cyclic precursor. In aqueous solution at 20 °C, (c-PNIPAM)-b-PCL self-assembles into spherical micelles consisting of hydrophobic PCL cores and well-solvated coronas of cyclic PNIPAM segments. For comparison, linear diblock copolymer with comparable molecular weight and composition, (l-PNIPAM)-b-PCL, was also synthesized. It was found that the thermoresponsive coronas of micelles self-assembled from (c-PNIPAM)-b-PCL exhibit thermoinduced collapse and aggregation at a lower critical thermal phase transition temperature (T(c)) compared with those of (l-PNIPAM)-b-PCL. Temperature-dependent drug release profiles from the two types of micelles of (c-PNIPAM)-b-PCL and (l-PNIPAM)-b-PCL loaded with doxorubicin (Dox) were measured, and the underlying mechanism for the observed difference in releasing properties was proposed. Moreover, MTT assays revealed that micelles of (c-PNIPAM)-b-PCL are almost noncytotoxic up to a concentration of 1.0 g/L, whereas at the same polymer concentration, micelles loaded with Dox lead to ∼60% cell death. Overall, chain topologies of thermoresponsive block copolymers, that is, (c-PNIPAM)-b-PCL versus (l-PNIPAM)-b-PCL, play considerable effects on the self-assembling and thermal phase transition properties and their functions as controlled release drug nanocarriers.

Transfer of fibroblast sheets cultured on thermoresponsive dishes with membranes.

PubMed

Kawecki, Marek; Kraut, Małgorzata; Klama-Baryła, Agnieszka; Łabuś, Wojciech; Kitala, Diana; Nowak, Mariusz; Glik, Justyna; Sieroń, Aleksander L; Utrata-Wesołek, Alicja; Trzebicka, Barbara; Dworak, Andrzej; Szweda, Dawid

2016-06-01

In cell or tissue engineering, it is essential to develop a support for cell-to-cell adhesion, which leads to the generation of cell sheets connected by extracellular matrix. Such supports must be hydrophobic and should result in a detachable cell sheet. A thermoresponsive support that enables the cultured cell sheet to detach using only a change in temperature could be an interesting alternative in regenerative medicine. The aim of this study was to evaluate plates covered with thermoresponsive polymers as supports for the formation of fibroblast sheets and to develop a damage-free procedure for cell sheet transfer with the use of membranes as transfer tools. Human skin fibroblasts were seeded on supports coated with a thermoresponsive polymer: commercial UpCell™ dishes (NUNC™) coated with thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) and dishes coated with thermoresponsive poly(tri(ethylene glycol) monoethyl ether methacrylate) (P(TEGMA-EE)). Confluent fibroblast sheets were effectively cultured and harvested from both commercial PNIPAM-coated dishes and laboratory P(TEGMA-EE)-coated dishes. To transfer a detached cell sheet, two membranes, Immobilon-P(®) and SUPRATHEL(®), were examined. The use of SUPRATHEL for relocating the cell sheets opens a new possibility for the clinical treatment of wounds. This study established the background for implementing thermoresponsive supports for transplanting in vitro cultured fibroblasts.

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.

Photo-crosslinkable polymers for fabrication of photonic multilayer sensors

NASA Astrophysics Data System (ADS)

Chiappelli, Maria; Hayward, Ryan C.

2013-03-01

We have used photo-crosslinkable polymers to fabricate photonic multilayer sensors. Benzophenone is utilized as a covalently incorporated pendent photo-crosslinker, providing a convenient means of fabricating multilayer films by sequential spin-coating and crosslinking processes. Colorimetric temperature sensors were designed from thermally-responsive, low-refractive index poly(N-isopropylacrylamide) (PNIPAM) and high-refractive index poly(para-methyl styrene) (P pMS). Copolymer chemistries and layer thicknesses were selected to provide robust multilayer sensors which show color changes across nearly the full visible spectrum due to changes in temperature of the hydrated film stack. We have characterized the uniformity and interfacial broadening within the multilayers, the kinetics of swelling and de-swelling, and the reversibility over multiple hydration/dehydration cycles. We also describe how the approach can be extended to alternative sensor designs through the ability to tailor each layer independently, as well as to additional stimuli by selecting alternative copolymer chemistries.

Double network physical gels from elastin-like polypeptide block copolymers: nanoscale control of thermoresponsive reinforcement

NASA Astrophysics Data System (ADS)

Glassman, Matthew; Olsen, Bradley

2014-03-01

Triblock copolymers with associative protein midblocks and thermoresponsive endblocks form shear thinning hydrogels with a low yield stress at low temperatures, but can be reinforced by a self-assembled network of the endblock aggregates. Here, we compare the use of bioengineered elastin-like polypeptides (ELPs) to synthetic poly(N-isopropylacrylamide) (PNIPAM) as endblocks to control the self-assembly of the reinforcing network. The temperature dependence of the mechanics of these hydrogels is a strong function of the domain size and morphology in the endblock network. Despite the architectural similarities, triblock ELP fusions and PNIPAM bioconjugates exhibit distinct reinforcement maxima at fixed block composition and polymer concentration, and these differences can be attributed to the nanostructural features of the two systems. Furthermore, in ELP fusions, the amino acid sequence can be readily modified to manipulate the solvation kinetics of the endblock domains. Finally, various endblocks have been combined to form triblock terpolymer hydrogels, demonstrating how the choice of thermoresponsive blocks can be used to tune the reinforcement of shear thinning hydrogels.

A facile construction of Au nanoparticles stabilized by thermo-responsive polymer-tethered carbon dots for enhanced catalytic performance

NASA Astrophysics Data System (ADS)

Li, Li; Zhang, Tianyi; Lü, Jianhua; Lü, Changli

2018-10-01

Carbon dots (CDs), the youngest member in the carbon nanomaterial family, have drawn considerable attention due to their interesting optical, physicochemical and electronic properties as well as broad promising applications. Here, we developed a facile and effective strategy for the preparation of Au nanoparticles stabilized by thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) functionalized carbon dots (Au@CD@P) under the gentle water media. The as-designed dopamine(DA)-terminated PNIPAM can be easily anchored to CDs via mussel-inspired chemistry route. Both CD@P and CDs could well stabilize the Au nanoparticles with interesting assembled structure. The as-prepared Au@CD and Au@CD@P nanohybrids with good dispersibility and stability exhibited the intriguing catalytic activity for reduction of p-nitrophenol (p-NP). Especially, Au@CD@P as catalyst also played a switching role in regulating the catalytic rate by temperature. In addition, Au@CD@P exhibited excellent recyclability which may have potential in green chemical industry for developing high-activity catalysts and easy production methods.

Programmable light-controlled shape changes in layered polymer nanocomposites.

PubMed

Zhu, Zhichen; Senses, Erkan; Akcora, Pinar; Sukhishvili, Svetlana A

2012-04-24

We present soft, layered nanocomposites that exhibit controlled swelling anisotropy and spatially specific shape reconfigurations in response to light irradiation. The use of gold nanoparticles grafted with a temperature-responsive polymer (poly(N-isopropylacrylamide), PNIPAM) with layer-by-layer (LbL) assembly allowed placement of plasmonic structures within specific regions in the film, while exposure to light caused localized material deswelling by a photothermal mechanism. By layering PNIPAM-grafted gold nanoparticles in between nonresponsive polymer stacks, we have achieved zero Poisson's ratio materials that exhibit reversible, light-induced unidirectional shape changes. In addition, we report rheological properties of these LbL assemblies in their equilibrium swollen states. Moreover, incorporation of dissimilar plasmonic nanostructures (solid gold nanoparticles and nanoshells) within different material strata enabled controlled shrinkage of specific regions of hydrogels at specific excitation wavelengths. The approach is applicable to a wide range of metal nanoparticles and temperature-responsive polymers and affords many advanced build-in options useful in optically manipulated functional devices, including precise control of plasmonic layer thickness, tunability of shape variations to the excitation wavelength, and programmable spatial control of optical response.

Thermo-responsive PNIPAM-metal hybrids: An efficient nanocatalyst for the reduction of 4-nitrophenol

NASA Astrophysics Data System (ADS)

Satapathy, Smith Sagar; Bhol, Prachi; Chakkarambath, Aswathy; Mohanta, Jagdeep; Samantaray, Kunal; Bhat, Suresh K.; Panda, Subhendu K.; Mohanty, Priti S.; Si, Satyabrata

2017-10-01

Micron size thermoresponsive cross-linked polymeric microgels of poly(N-isopropylacrylamide) (PNIPAM) are used as "microreactor" for embedding metal nanoparticles of different shapes. Using a simple and robust method, we have synthesized various polymer-metal hybrid nanostructures incorporated with Au nanorods (AuNR), Au nanospheres (AuNS) and Ag nanospheres (AgNS). These hybrid nanostructures have been characterized by transmission electron microscope (TEM), UV-vis spectroscopy, dynamic light scattering (DLS) and static light scattering (SLS) followed by their catalytic activity. TEM studies directly confirmed the mondispersity of synthesized hybrid microgels and stability of the embedded metal nanoparticles within the microgels. Optical studies confirmed the presence of respective absorption bands that correspond to AuNS, AgNS and AuNR respectively. Extensive DLS studies demonstrated that although these hybrid microgels preserve their thermoresponsive properties, i.e their hydrodynamic radius decreased with increasing temperature, their thermosensitivity were comparatively lesser than pure PNIPAM microgels. Combining with studies using static light scattering, we further found that AuNS and AgNS were inhomogeneously distributed within microgels where the majority of the nanoparticles present within the loosely cross-linked shell. On the other hand AuNR were distributed more homogeneously within the microgels. Catalytic performance of various nanostructures loaded onto PNIPAM microgel beads were evaluated by studying the catalytic reduction of 4-nitrophenol. Complete catalytic conversion using AgNS occurred in ∼30 min with a first-order rate constant of 0.159 min-1 having a 7 min induction period. On the other hand no induction period was observed for AuNS and AuNR and the reaction completed in 3-4 min with a first-order rate constant of 1.607 min-1 and 1.627 min-1 respectively. Further, PNIPAM-AuNS and PNIPAM-AuNR possess better catalytic activity as well as recyclability compared to that of PNIPAM-AgNS.

Thermo-sensitive nanoparticles for triggered release of siRNA.

PubMed

Yang, Zheng; Cheng, Qiang; Jiang, Qian; Deng, Liandong; Liang, Zicai; Dong, Anjie

2015-01-01

Efficient delivery of small interfering RNA (siRNA) is crucially required for cancer gene therapy. Herein, a thermo-sensitive copolymer with a simple structure, poly (ethylene glycol) methyl ether acrylate-b-poly (N-isopropylacrylamide) (mPEG-b-PNIPAM) was developed. A novel kind of thermo-sensitive nanoparticles (DENPs) was constructed for the cold-shock triggered release of siRNA by double emulsion-solvent evaporation method using mPEG-b-PNIPAM and a cationic lipid, 3β [N-(N', N'-dimethylaminoethane)-carbamoyl] cholesterol [DC-Chol]. DENPs were observed by transmission electron microscopy and dynamical light scattering before and after 'cold shock' treatment. The encapsulation efficiency (EE) of siRNA in DENPs, which was measured by fluorescence spectrophotometer was 96.8% while it was significantly reduced to be 23.2% when DC-Chol was absent. DENPs/siRNA NPs exhibited a thermo-sensitive siRNA release character that the cumulatively released amount of siRNA from cold shock was approximately 2.2 folds higher after 7 days. In vitro luciferase silencing experiments indicated that DENPs showed potent gene silencing efficacy in HeLa-Luc cells (HeLa cells steadily expressed luciferase), which was further enhanced by a cold shock. Furthermore, MTT assay showed that cell viability with DENPs/siRNA up to 200 nM remained above 80%. We also observed that most of siRNA was accumulated in kidney mediated by DENPs instead of liver and spleen in vivo experiments. Thus, DENPs as a cold shock responsive quick release model for siRNA or hydrophilic macromolecules delivery provide a new way to nanocarrier design and clinic therapy.

A remotely operated drug delivery system with an electrolytic pump and a thermo-responsive valve

PubMed Central

Yi, Ying; Zaher, Amir; Yassine, Omar; Kosel, Jurgen; Foulds, Ian G.

2015-01-01

Implantable drug delivery devices are becoming attractive due to their abilities of targeted and controlled dose release. Currently, two important issues are functional lifetime and non-controlled drug diffusion. In this work, we present a drug delivery device combining an electrolytic pump and a thermo-responsive valve, which are both remotely controlled by an electromagnetic field (40.5 mT and 450 kHz). Our proposed device exhibits a novel operation mechanism for long-term therapeutic treatments using a solid drug in reservoir approach. Our device also prevents undesired drug liquid diffusions. When the electromagnetic field is on, the electrolysis-induced bubble drives the drug liquid towards the Poly (N-Isopropylacrylamide) (PNIPAM) valve that consists of PNIPAM and iron micro-particles. The heat generated by the iron micro-particles causes the PNIPAM to shrink, resulting in an open valve. When the electromagnetic field is turned off, the PNIPAM starts to swell. In the meantime, the bubbles are catalytically recombined into water, reducing the pressure inside the pumping chamber, which leads to the refilling of the fresh liquid from outside the device. A catalytic reformer is included, allowing more liquid refilling during the limited valve's closing time. The amount of body liquid that refills the drug reservoir can further dissolve the solid drug, forming a reproducible drug solution for the next dose. By repeatedly turning on and off the electromagnetic field, the drug dose can be cyclically released, and the exit port of the device is effectively controlled. PMID:26339328

Fabrication of High-Sensitivity Skin-Attachable Temperature Sensors with Bioinspired Microstructured Adhesive.

PubMed

Oh, Ju Hyun; Hong, Soo Yeong; Park, Heun; Jin, Sang Woo; Jeong, Yu Ra; Oh, Seung Yun; Yun, Junyeong; Lee, Hanchan; Kim, Jung Wook; Ha, Jeong Sook

2018-02-28

In this study, we demonstrate the fabrication of a highly sensitive flexible temperature sensor with a bioinspired octopus-mimicking adhesive. A resistor-type temperature sensor consisting of a composite of poly(N-isopropylacrylamide) (pNIPAM)-temperature sensitive hydrogel, poly(3,4-ethylenedioxythiophene) polystyrene sulfonate, and carbon nanotubes exhibits a very high thermal sensitivity of 2.6%·°C -1 between 25 and 40 °C so that the change in skin temperature of 0.5 °C can be accurately detected. At the same time, the polydimethylsiloxane adhesive layer of octopus-mimicking rim structure coated with pNIPAM is fabricated through the formation of a single mold by utilizing undercut phenomenon in photolithography. The fabricated sensor shows stable and reproducible detection of skin temperature under repeated attachment/detachment cycles onto skin without any skin irritation for a long time. This work suggests a high potential application of our skin-attachable temperature sensor to wearable devices for medical and health-care monitoring.

Diblock Terpolymers Are Tunable and pH Responsive Vehicles To Increase Hydrophobic Drug Solubility for Oral Administration.

PubMed

Tale, Swapnil; Purchel, Anatolii A; Dalsin, Molly C; Reineke, Theresa M

2017-11-06

Synthetic polymers offer tunable platforms to create new oral drug delivery vehicles (excipients) to increase solubility, supersaturation maintenance, and bioavailability of poorly aqueous soluble pharmaceutical candidates. Five well-defined diblock terpolymers were synthesized via reversible addition-fragmentation chain transfer polymerization (RAFT) and consist of a first block of either poly(ethylene-alt-propylene) (PEP), poly(N-isopropylacrylamide) (PNIPAm), or poly(N,N-diethylaminoethyl methacrylate) (PDEAEMA) and a second hydrophilic block consisting of a gradient copolymer of N,N-dimethylacrylamide (DMA) and 2-methacrylamidotrehalose (MAT). This family of diblock terpolymers offers hydrophobic, hydrophilic, or H-bonding functionalities to serve as noncovalent sites of drug binding. Drug-polymer spray dried dispersions (SDDs) were created with a model drug, probucol, and characterized by differential scanning calorimetry (DSC). These studies revealed that probucol crystallinity decreased with increasing H-bonding sites available in the polymer. The PNIPAm-b-P(DMA-grad-MAT) systems revealed the best performance at pH 6.5, where immediate probucol release and effective maintenance of 100% supersaturation was found, which is important for facilitating drug solubility in more neutral conditions (intestinal environment). However, the PDEAEMA-b-P(DMA-grad-MAT) system revealed poor probucol dissolution at pH 6.5 and 5.1. Alternatively, at an acidic pH of 3.1, a rapid and high dissolution profile and effective supersaturation maintenance of up to 90% of the drug was found, which could be useful for triggering drug release in acidic environments (stomach). The PEP-b-P(DMA-grad-MAT) system showed poor performance (only ∼20% of drug solubility at pH 6.5), which was attributed to the low solubility of the polymers in the dissolution media. This work demonstrates the utility of diblock terpolymers as a potential new excipient platform to optimize design parameters for triggered release and solubilizing hydrophobic drug candidates for oral delivery.

Aggregation of Culture Expanded Human Mesenchymal Stem Cells in Microcarrier-based Bioreactor.

PubMed

Yuan, Xuegang; Tsai, Ang-Chen; Farrance, Iain; Rowley, Jon; Ma, Teng

2018-03-15

Three-dimensional aggregation of human mesenchymal stem cells (hMSCs) has been used to enhance their therapeutic properties but current fabrication protocols depend on laboratory methods and are not scalable. In this study, we developed thermal responsive poly(N-isopropylacrylamide) grafted microcarriers (PNIPAM-MCs), which supported expansion and thermal detachment of hMSCs at reduced temperature (23.0 °C). hMSCs were cultured on the PNIPAM-MCs in both spinner flask (SF) and PBS Vertical-Wheel (PBS-VW) bioreactors for expansion. At room temperature, hMSCs were detached as small cell sheets, which subsequently self-assembled into 3D hMSC aggregates in PBS-VW bioreactor and remain as single cells in SF bioreactor owing to different hydrodynamic conditions. hMSC aggregates generated from the bioreactor maintained comparable immunomodulation and cytokine secretion properties compared to the ones made from the AggreWell ® . The results of the current study demonstrate the feasibility of scale-up production of hMSC aggregates in the suspension bioreactor using thermal responsive microcarriers for integrated cell expansion and 3D aggregation in a close bioreactor system and highlight the critical role of hydrodynamics in self-assembly of detached hMSC in suspension.

Vesicular gold assemblies based on host-guest inclusion and its controllable release of doxorubicin

NASA Astrophysics Data System (ADS)

Ha, Wei; Kang, Yang; Peng, Shu-Lin; Ding, Li-Sheng; Zhang, Sheng; Li, Bang-Jing

2013-12-01

We have developed a kind of gold nanoparticle (AuNP) in which polyethylene glycol (PEG) and poly(N-isopropylacrylamide) (PNIPAM) are attached on the surface of a gold nanocrystal through the host-guest inclusion between adamantane groups (ADA) and β-cyclodextrin (β-CD). The resulting AuNPs become amphiphilic in water above body temperature and self-assemble into vesicles. It is found that these vesicles can load doxorubicin (Dox) effectively. With a decrease in temperature, the PNIPAM shifted from hydrophobic to hydrophilic, causing Au vesicles to disassemble into stable small AuNPs, triggering the release of Dox. These hybrid vesicles, combining polymer functionality with the intriguing properties of AuNPs, can first release free Dox and AuNP/Dox at a site of a tumor through the application of either simple ice packs or deeply penetrating cryoprobes, then the AuNP/Dox can be taken in by tumor cells and destroy them like miniature munitions. Furthermore, these vesicles showed other therapeutic possibilities due to the presence of gold. We believe that the development of such multi-functional vesicles will provide new and therapeutically useful means for medical applications.

Triggering the volume phase transition of core-shell Au nanorod-microgel nanocomposites with light

NASA Astrophysics Data System (ADS)

Rodríguez-Fernández, Jessica; Fedoruk, Michael; Hrelescu, Calin; Lutich, Andrey A.; Feldmann, Jochen

2011-06-01

We have coated gold nanorods (NRs) with thermoresponsive microgel shells based on poly(N-isopropylacrylamide) (pNIPAM). We demonstrate by simultaneous laser-heating and optical extinction measurements that the Au NR cores can be simultaneously used as fast optothermal manipulators (switchers) and sensitive optical reporters of the microgel state in a fully externally controlled and reversible manner. We support our results with optical modeling based on the boundary element method and 3D numerical analysis on the temperature distribution. Briefly, we show that due to the sharp increase in refractive index resulting from the optothermally triggered microgel collapse, the longitudinal plasmon band of the coated Au NRs is significantly red-shifted. The optothermal control over the pNIPAM shell, and thereby over the optical response of the nanocomposite, is fully reversible and can be simply controlled by switching on and off a NIR heating laser. In contrast to bulk solution heating, we demonstrate that light-triggering does not compromise colloidal stability, which is of primary importance for the ultimate utilization of these types of nanocomposites as remotely controlled optomechanical actuators, for applications spanning from drug delivery to photonic crystals and nanoscale motion.

Tuning the structure of thermosensitive gold nanoparticle monolayers.

PubMed

Rezende, Camila A; Shan, Jun; Lee, Lay-Theng; Zalczer, Gilbert; Tenhu, Heikki

2009-07-23

Gold nanoparticles grafted with poly(N-isopropylacrylamide) (PNIPAM) are rendered amphiphilic and thermosensitive. When spread on the surface of water, they form stable Langmuir monolayers that exhibit surface plasmon resonance. Using Langmuir balance and contrast-matched neutron reflectivity, the detailed structural properties of these nanocomposite monolayers are revealed. At low surface coverage, the gold nanoparticles are anchored to the interface by an adsorbed PNIPAM layer that forms a thin and compact pancake structure. Upon isothermal compression (T=20 degrees C), the adsorbed layer thickens with partial desorption of polymer chains to form brush structures. Two distinct polymer conformations thus coexist: an adsorbed conformation that assures stability of the monolayer, and brush structures that dangle in the subphase. An increase in temperature to 30 degrees C results in contractions of both adsorbed and brush layers with a concomitant decrease in interparticle distance, indicating vertical as well as lateral contractions of the graft polymer layer. The reversibility of this thermal response is also shown by the contraction-expansion of the polymer layers in heating-cooling cycles. The structure of the monolayer can thus be tuned by compression and reversibly by temperature. These compression and thermally induced conformational changes are discussed in relation to optical properties.

Thermoresponsive electrospun fibers for water harvesting applications

NASA Astrophysics Data System (ADS)

Thakur, Neha; Baji, Avinash; Ranganath, Anupama Sargur

2018-03-01

Temperature triggered switchable cellulose acetate-poly(N-isopropylacrylamide) (CA-PNIPAM) core-shell and blend nanofibers are fabricated for controlled moisture harvesting applications. Core-shell fibers are fabricated using a co-axial electrospinning setup whereas the conventional electrospinning setup is employed for fabricating the blend fibers. Investigation of their wettability behaviour demonstrated that the blend fibers are superhydrophilic whereas the core-shell fibers are hydrophilic at ambient temperature. Furthermore, both the samples have an ability to switch between the two states viz. hydrophilic to hydrophobic state based on thermal stimulus. The core-shell fibers are shown to have higher moisture sorption ability compared to the blend fibers. This study investigates the mechanism behind the switchable wettability behaviour of the core-shell fibers and demonstrates the crucial role played by the functional groups present on the surface layer of fibers in governing their moisture collection efficiency.

Thermo-responsive plasmonic nanohybrids with tunable optical properties

NASA Astrophysics Data System (ADS)

Zhang, Lingyu; Song, Gang

2017-10-01

In this paper, we study the temperature-dependent optical properties of gold-silver core-shell (Au@Ag) nanorods coated by a thermo-responsive polymer poly (N-isopropylacrylamide) (PNIPAM). The wavelength of the plasmonic resonant absorption of the nanohybrids changes with temperature due to the combination effects of the plasmon resonance of the core and the thermal response of the shell. Using effective medium theory, we find that with increase of temperature, the absorption peak red-shifts due to the competition effects from the changes of the thickness and the effective refractive index of the polymer shell. The working wavelength can be tuned by the aspect ratio of nanorods. Moreover, the temperature sensitivity of plasmon resonance increases with the increase of the aspect ratio. Our studies provide a proof-of-concept design of thermal responsive plasmonic smart material.

Tuning the bridging attraction between large hard particles by the softness of small microgels.

PubMed

Luo, Junhua; Yuan, Guangcui; Han, Charles C

2016-09-20

In this study, the attraction between large hard polystyrene (PS) spheres is studied by using three types of small microgels as bridging agents. One is a purely soft poly(N-isopropylacrylamide) (PNIPAM) microgel, the other two have a non-deformable PS hard core surrounded by a soft PNIPAM shell but are different in the core-shell ratio. The affinity for bridging the large PS spheres is provided and thus affected by the PNIPAM constituent in the microgels. The bridging effects caused by the microgels can be indirectly incorporated into their influence on the effective attraction interaction between the large hard spheres, since the size of the microgels is very small in comparison to the size of the PS hard spheres. At a given volume fraction of large PS spheres, they behave essentially as hard spheres in the absence of small microgels. By gradually adding the microgels, the large spheres are connected to each other through the bridging of small particles until the attraction strength reaches a maximum value, after which adding more small particles slowly decreases the effective attraction strength and eventually the large particles disperse individually when saturated adsorption is achieved. The aggregation and gelation behaviors triggered by these three types of small microgels are compared and discussed. A way to tune the strength and range of the short-range attractive potential via changing the softness of bridging microgels (which can be achieved either by using core-shell microgels or by changing the temperature) is proposed.

Smart polyaniline nanoparticles with thermal and photothermal sensitivity

NASA Astrophysics Data System (ADS)

Bongiovanni Abel, Silvestre; Molina, María A.; Rivarola, Claudia R.; Kogan, Marcelo J.; Barbero, Cesar A.

2014-12-01

Conductive polyaniline nanoparticles (PANI NPs) are synthesized by oxidation of aniline with persulfate in acid media, in the presence of polymeric stabilizers: polyvinilpyrrolidone (PVP), poly(N-isopropylacrylamide) (PNIPAM), and hydroxylpropylcellulose (HPC). It is observed that the size of the nanoparticles obtained depends on the polymeric stabilizer used, suggesting a mechanism where the aggregation of polyaniline molecules is arrested by adsorption of the polymeric stabilizer. Indeed, polymerization in the presence of a mixture of two polymers having different stabilizing capacity (PVP and PNIPAM) allows tuning of the size of the nanoparticles. Stabilization with biocompatible PVP, HPC and PNIPAM allows use of the nanoparticle dispersions in biological applications. The nanoparticles stabilized by thermosensitive polymers (PNIPAM and HPC) aggregate when the temperature exceeds the phase transition (coil to globule) temperature of each stabilizer (Tpt = 32 °C for PNIPAM or Tpt = 42 °C for HPC). This result suggests that an extended coil form of the polymeric stabilizer is necessary to avoid aggregation. The dispersions are reversibly restored when the temperature is lowered below Tpt. In that way, the effect could be used to separate the nanoparticles from soluble contaminants. On the other hand, the PANI NPs stabilized with PVP are unaffected by the temperature change. UV-visible spectroscopy measurements show that the nanoparticle dispersion changes their spectra with the pH of the external solution, suggesting that small molecules can easily penetrate the stabilizer shell. Near infrared radiation is absorbed by PANI NPs causing an increase of their temperature which induces the collapse of the thermosensitive polymer shell and aggregation of the NPs. The effect reveals that it is possible to locally heat the nanoparticles, a phenomenon that can be used to destroy tumor cells in cancer therapy or to dissolve protein aggregates of neurodegenerative diseases (e.g. Alzheimer). Moreover, the long range control of aggregation can be used to modulate the nanoparticle residence inside biological tissues.

Visualizing phase transition behavior of dilute stimuli responsive polymer solutions via Mueller matrix polarimetry.

PubMed

Narayanan, Amal; Chandel, Shubham; Ghosh, Nirmalya; De, Priyadarsi

2015-09-15

Probing volume phase transition behavior of superdiluted polymer solutions both micro- and macroscopically still persists as an outstanding challenge. In this regard, we have explored 4 × 4 spectral Mueller matrix measurement and its inverse analysis for excavating the microarchitectural facts about stimuli responsiveness of "smart" polymers. Phase separation behavior of thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) and pH responsive poly(N,N-(dimethylamino)ethyl methacrylate) (PDMAEMA) and their copolymers were analyzed in terms of Mueller matrix derived polarization parameters, namely, depolarization (Δ), diattenuation (d), and linear retardance (δ). The Δ, d, and δ parameters provided useful information on both macro- and microstructural alterations during the phase separation. Additionally, the two step action ((i) breakage of polymer-water hydrogen bonding and (ii) polymer-polymer aggregation) at the molecular microenvironment during the cloud point generation was successfully probed via these parameters. It is demonstrated that, in comparison to the present techniques available for assessing the hydrophobic-hydrophilic switch over of simple stimuli-responsive polymers, Mueller matrix polarimetry offers an important advantage requiring a few hundred times dilute polymer solution (0.01 mg/mL, 1.1-1.4 μM) at a low-volume format.

In vivo imaging of the morphology and changes in pH along the gastrointestinal tract of Japanese medaka by photonic band-gap hydrogel microspheres.

PubMed

Du, Xuemin; Lei, Ngai-Yu; Hu, Peng; Lei, Zhang; Ong, Daniel Hock-Chun; Ge, Xuewu; Zhang, Zhicheng; Lam, Michael Hon-Wah

2013-07-17

Colloidal crystalline microspheres with photonic band-gap properties responsive to media pH have been developed for in vivo imaging purposes. These colloidal crystalline microspheres were constructed from monodispersed core-shell nano-size particles with poly(styrene-co-acrylic acid) (PS-co-PAA) cores and poly(acrylic acid-co-N-isopropylacrylamide) (PAA-co-PNIPAM) hydrogel shells cross-linked by N,N'-methylenebisacrylamide. A significant shift in the photonic band-gap properties of these colloidal crystalline microspheres was observed in the pH range of 4-5. This was caused by the discontinuous volume phase transition of the hydrogel coating, due to the protonation/deprotonation of its acrylic acid moieties, on the core-shell nano-sized particles within the microspheres. The in vivo imaging capability of these pH-responsive photonic microspheres was demonstrated on a test organism - Japanese medaka, Oryzia latipes - in which the morphology and change in pH along their gastrointestinal (GI) tracts were revealed under an ordinary optical microscope. This work illustrates the potential of stimuli-responsive photonic band-gap materials in tissue-/organ-level in vivo bio-imaging. Copyright © 2013 Elsevier B.V. All rights reserved.

Comprehensive Computational and Experimental Analysis of Biomaterial toward the Behavior of Imidazolium-Based Ionic Liquids: An Interplay between Hydrophilic and Hydrophobic Interactions.

PubMed

Umapathi, Reddicherla; Vepuri, Suresh B; Venkatesu, Pannuru; Soliman, Mahmoud E

2017-05-11

To provide insights into the aggregation behavior, hydration tendency and variation in phase transition temperature produced by the addition of ionic liquids (ILs) to poly(N-isopropylacrylamide) (PNIPAM) aqueous solution, systematic physicochemical studies, and molecular dynamic simulations were carried out. The influence of ILs possessing the same [Cl] - anion and a set of cations [C n mim] + with increasing alkyl chain length such as 1-ethyl-3-methylimidazolium ([Emim] + ), 1-allyl-3-methylimidazolium ([Amim] + ), 1-butyl-3-methylimidazolium ([Bmim] + ), 1-hexyl-3-methylimidazolium ([Hmim] + ), 1-benzyl-3-methylimidazolium ([Bzmim] + ), and 1-decyl-3-methylimidazolium ([Dmim] + ) on the phase transition of PNIPAM was monitored by the aid of UV-visible absorption spectra, fluorescence intensity spectra, viscosity (η), dynamic light scattering (DLS), and Fourier transform infrared (FTIR) spectroscopy. Furthermore, to interpret the direct images and surface morphologies of the PNIPAM-IL aggregates, we performed field emission scanning electron microscopy (FESEM). The overall specific ranking of ILs in preserving the hydration layer around the PNIPAM aqueous solution was [Emim][Cl] > [Amim][Cl] > [Bmim][Cl] > [Hmim][Cl] > [Bzmim][Cl] > [Dmim][Cl]. Moreover, to investigate the molecular mechanism behind the change in the lower critical solution temperature (LCST) of the polymer in the presence of the ILs, a molecular dynamics (MD) study was performed. The MD simulation has clearly shown the reduction in hydration shell of the polymer after interacting with the ILs at their respective LCST. MD study revealed significant changes in polymer conformation because of IL interactions and strongly supports the experimental observation of polymer phase transition at a temperature lower than typical LCST for all the studied ILs. The driving force for concomitant sharp configurational transition has been attributed to the displacement of water molecules on the polymer surface by the ILs because of their hydrophobic interaction with the polymer.

Synthesis and Self-Assembly of Block Copolymers Containing Temperature Sensitive and Degradable Chain Segments.

PubMed

Gong, Hong-Liang; Lei, Lei; Shi, Shu-Xian; Xia, Yu-Zheng; Chen, Xiao-Nong

2018-05-01

In this work, polylactide-b-poly(N-isopropylacrylamide) were synthesized by the combination of controlled ring-opening polymerization and reversible addition fragmentation chain transfer polymerization. These block copolymers with molecular weight range from 7,900 to 12,000 g/mol and narrow polydispersity (≤1.19) can self-assemble into micelles (polylactide core, poly(N-isopropylacrylamide) shell) in water at certain temperature range, which have been evidenced by laser particle size analyzer proton nuclear magnetic resonance and transmission electron microscopy. Such micelles exhibit obvious thermo-responsive properties: (1) Poly(N-isopropylacrylamide) blocks collapse on the polylactide core as system temperature increase, leading to reduce of micelle size. (2) Micelles with short poly(N-isopropylacrylamide) blocks tend to aggregate together when temperature increased, which is resulted from the reduction of the system hydrophilicity and the decreased repulsive force between micelles.

Angle selective backscattered electron contrast in the low-voltage scanning electron microscope: Simulation and experiment for polymers.

PubMed

Wan, Q; Masters, R C; Lidzey, D; Abrams, K J; Dapor, M; Plenderleith, R A; Rimmer, S; Claeyssens, F; Rodenburg, C

2016-12-01

Recently developed detectors can deliver high resolution and high contrast images of nanostructured carbon based materials in low voltage scanning electron microscopes (LVSEM) with beam deceleration. Monte Carlo Simulations are also used to predict under which exact imaging conditions purely compositional contrast can be obtained and optimised. This allows the prediction of the electron signal intensity in angle selective conditions for back-scattered electron (BSE) imaging in LVSEM and compares it to experimental signals. Angle selective detection with a concentric back scattered (CBS) detector is considered in the model in the absence and presence of a deceleration field, respectively. The validity of the model prediction for both cases was tested experimentally for amorphous C and Cu and applied to complex nanostructured carbon based materials, namely a Poly(N-isopropylacrylamide)/Poly(ethylene glycol) Diacrylate (PNIPAM/PEGDA) semi-interpenetration network (IPN) and a Poly(3-hexylthiophene-2,5-diyl) (P3HT) film, to map nano-scale composition and crystallinity distribution by avoiding experimental imaging conditions that lead to a mixed topographical and compositional contrast. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Polymer collapse in miscible good solvents is a generic phenomenon driven by preferential adsorption

PubMed Central

Mukherji, Debashish; Marques, Carlos M.; Kremer, Kurt

2014-01-01

Water and alcohol, such as methanol or ethanol, are miscible and, individually, good solvents for poly(N-isopropylacrylamide) (PNIPAm), but this polymer precipitates in water–alcohol mixtures. The intriguing behaviour of solvent mixtures that cannot dissolve a given polymer or a given protein, while the same macromolecule dissolves well in each of the cosolvents, is called cononsolvency. It is a widespread phenomenon, relevant for many formulation steps in the physicochemical and pharmaceutical industry, that is usually explained by invoking specific chemical details of the mixtures: as such, it has so far eluded any generic explanation. Here, by using a combination of simulations and theory, we present a simple and universal treatment that requires only the preferential interaction of one of the cosolvents with the polymer. The results show striking quantitative agreement with experiments and chemically specific simulations, opening a new perspective towards an operational understanding of macromolecular solubility. PMID:25216245

Humidity-Responsive Gold Aerogel for Real-Time Monitoring of Human Breath.

PubMed

Ali, Israt; Chen, Liming; Huang, Youju; Song, Liping; Lu, Xuefei; Liu, Baoqing; Zhang, Lei; Zhang, Jiawei; Hou, Linxi; Chen, Tao

2018-04-24

Humidity sensors have received considerable attention in recent years because of their significance and wide applications in agriculture, industries, goods stores, and medical fields. However, the conventional humidity sensors usually possessed a complex sensing mechanism and low sensitivity and required a time-consuming, labor-intensive process. The exploration for an ideal sensing material to amplify the sensitivity of humidity sensors is still a big challenge. Herein, we developed a simple, low-cost, and scalable fabrication strategy to construct a highly sensitive humidity sensor based on polymer/gold nanoparticle (AuNP) hybrid materials. The hybrid polymer/AuNP aerogel was prepared by a simple freeze-drying method. By taking advantage of the conductivity of AuNPs and high surface area of the highly porous structure, the hybrid poly- N-isopropylacrylamide (PNIPAm)/AuNP aerogel showed high sensitivity to water molecules. Interestingly, the hybrid PNIPAm/AuNP aerogel-based humidity sensor can be used to detect human breath in different states, such as normal breath, fast breath, and deep breath, or in different individuals such as persons with illness, persons who are smoking, and persons who are normal, which is promising in practical flexible wearable devices for human health monitoring. In addition, the humidity sensor can be used in whistle tune recognition.

Specificity in cationic interaction with poly(N-isopropylacrylamide).

PubMed

Du, Hongbo; Wickramasinghe, Sumith Ranil; Qian, Xianghong

2013-05-02

Classical molecular dynamics (MD) simulations were conducted for PNIPAM in 1 M monovalent alkali chloride salt solutions as well as in 0.5 M divalent Mg(2+) and Ca(2+) chloride salt solutions. It was found that the strength for the direct alkali ion-amide O binding is strongly correlated with the size of the ionic radius. The smallest Li(+) ion binds strongest to amide O, and the largest Cs(+) ion has the weakest interaction with the amide bond. For the divalent Mg(2+) and Ca(2+) ions, their interactions with the amide bond are weak and appear to be mediated by the water molecules, particularly in the case of Mg(2+), resulting from their strong hydration. The direct binding between the cations and amide O requires partial desovlation of the ions that is energetically unfavorable for Mg(2+) and also to a great extent for Ca(2+). The higher cation charge makes the electrostatic interaction more favorable but the dehydration process less favorable. This competition between electrostatic interaction and the dehydration process largely dictates whether the direct binding between the cation and amide O is energetically preferred or not. For monovalent alkali ions, it is energetically preferred to bind directly with the amide O. Moreover, Li(+) ion is also found to associate strongly with the hydrophobic residues on PNIPAM.

In-depth analysis of switchable glycerol based polymeric coatings for cell sheet engineering.

PubMed

Becherer, Tobias; Heinen, Silke; Wei, Qiang; Haag, Rainer; Weinhart, Marie

2015-10-01

Scaffold-free cell sheet engineering using thermoresponsive substrates provides a promising alternative to conventional tissue engineering which in general employs biodegradable scaffold materials. We have previously developed a thermoresponsive coating with glycerol based linear copolymers that enables gentle harvesting of entire cell sheets. In this article we present an in-depth analysis of these thermoresponsive linear polyglycidyl ethers and their performance as coating for substrates in cell culture in comparison with commercially available poly(N-isopropylacrylamide) (PNIPAM) coated culture dishes. A series of copolymers of glycidyl methyl ether (GME) and glycidyl ethyl ether (EGE) was prepared in order to study their thermoresponsive properties in solution and on the surface with respect to the comonomer ratio. In both cases, when grafted to planar surfaces or spherical nanoparticles, the applied thermoresponsive polyglycerol coatings render the respective surfaces switchable. Protein adsorption experiments on copolymer coated planar surfaces with surface plasmon resonance (SPR) spectroscopy reveal the ability of the tested thermoresponsive coatings to be switched between highly protein resistant and adsorptive states. Cell culture experiments demonstrate that these thermoresponsive coatings allow for adhesion and proliferation of NIH 3T3 fibroblasts comparable to TCPS and faster than on PNIPAM substrates. Temperature triggered detachment of complete cell sheets from copolymer coated substrates was accomplished within minutes while maintaining high viability of the harvested cells. Thus such glycerol based copolymers present a promising alternative to PNIPAM as a thermoresponsive coating of cell culture substrates. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Self-Assembly of pH-Responsive Microspheres for Intestinal Delivery of Diverse Lipophilic Therapeutics.

PubMed

Zhou, Xing; Zhao, Yang; Chen, Siyu; Han, Songling; Xu, Xiaoqiu; Guo, Jiawei; Liu, Mengyu; Che, Ling; Li, Xiaohui; Zhang, Jianxiang

2016-08-08

Targeted delivery of therapeutics to the intestine is preferred for the management of many diseases due to its diverse advantages. Currently, there are still challenges in creating cost-effective and translational pH-responsive microspheres for intestinal delivery of various hydrophobic drugs. Herein we report a multiple noncovalent interactions-mediated assembly strategy in which carboxyl-bearing compounds (CBCs) are guest molecules, while poly(N-isopropylacrylamide) (PNIPAm) serves as a host polymer. Formation of microparticles and therapeutic packaging can be achieved simultaneously by this assembly approach, leading to well-shaped microspheres with extremely higher drug loading capacity as compared to microspheres based on two FDA-approved materials of poly(d,l-lactide-co-glycolide) (PLGA) and an enteric coating polymer EudragitS 100 (S100). Also, carboxyl-deficient hydrophobic drugs can be effectively entrapped. These assembled microspheres, with excellent reconstitution capability as well as desirable scalability, could selectively release drug molecules under intestinal conditions. By significantly enhancing drug dissolution/release in the intestine, these pH-responsive assemblies may notably improve the oral bioavailability of loaded therapeutics. Moreover, the assembled microspheres possessed superior therapeutic performance in rodent models of inflammation and tumor over the control microspheres derived from PLGA and S100. Therapy with newly developed microspheres did not cause undesirable side effects. Furthermore, in vivo evaluation in mice revealed the carrier material PNIPAm was safe for oral delivery at doses as high as 10 g/kg. Collectively, our findings demonstrated that this type of pH-responsive microsphere may function as superior and translational intestine-directed delivery systems for a diverse array of therapeutics.

Poly(N-Isopropylacrylamide)-co-Acrylamide Hydrogels for the Controlled Release of Bromelain from Agroindustrial Residues of Ananas comosus.

PubMed

Croisfelt, Fernanda; Martins, Bianca C; Rescolino, Robson; Coelho, Diego F; Zanchetta, Beatriz; Mazzola, Priscila G; Goulart, Luis Ricardo; Pessoa, Adalberto; Tambourgi, Elias B; Silveira, Edgar

2015-12-01

This works reports the purification of bromelain extracted from Ananas comosus industrial residues by ethanol purification, its partial characterization from the crude extract as well as the ethanol purified enzyme, and its application onto poly(N-isopropylacrylamide)-co-acrylamide hydrogels. Bromelain was recovered within the 30-70 % ethanol fraction, which achieved a purification factor of 3.12-fold, and yielded more than 90 % of its initial activity. The resulting purified bromelain contained more than 360 U · mg(-1), with a maximum working temperature of 60 °C and pH of 8.0. Poly(N-isopropylacrylamide)-co-acrylamide hydrogels presented a swelling rate of 125 %, which was capable of loading 56 % of bromelain from the solution, and was able to release up to 91 % of the retained bromelain. Ethanol precipitation is suitable for bromelain recovery and application onto poly(N-isopropylacrylamide)-co-acrylamide hydrogels based on its processing time and the applied ethanol prices. Georg Thieme Verlag KG Stuttgart · New York.

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.

Activation of Actuating Hydrogels with WS2 Nanosheets for Biomimetic Cellular Structures and Steerable Prompt Deformation.

PubMed

Zong, Lu; Li, Xiankai; Han, Xiangsheng; Lv, Lili; Li, Mingjie; You, Jun; Wu, Xiaochen; Li, Chaoxu

2017-09-20

Macroscopic soft actuation is intrinsic to living organisms in nature, including slow deformation (e.g., contraction, bending, twisting, and curling) of plants motivated by microscopic swelling and shrinking of cells, and rapid motion of animals (e.g., deformation of jellyfish) motivated by cooperative nanoscale movement of motor proteins. These actuation behaviors, with an exceptional combination of tunable speed and programmable deformation direction, inspire us to design artificial soft actuators for broad applications in artificial muscles, nanofabrication, chemical valves, microlenses, soft robotics, etc. However, so far artificial soft actuators have been typically produced on the basis of poly(N-isopropylacrylamide) (PNiPAM), whose deformation is motived by volumetric shrinkage and swelling in analogue to plant cells, and exhibits sluggish actuation kinetics. In this study, alginate-exfoliated WS 2 nanosheets were incorporated into ice-template-polymerized PNiPAM hydrogels with the cellular microstructures which mimic plant cells, yet the prompt steerable actuation of animals. Because of the nanosheet-reinforced pore walls formed in situ in freezing polymerization and reasonable hierarchical water channels, this cellular hybrid hydrogel achieves super deformation speed (on the order of magnitude of 10° s), controllable deformation direction, and high near-infrared light responsiveness, offering an unprecedented platform of artificial muscles for various soft robotics and devices (e.g., rotator, microvalve, aquatic swimmer, and water-lifting filter).

Thermoresponsive magnetic composite nanomaterials for multimodal cancer therapy.

PubMed

Purushotham, S; Ramanujan, R V

2010-02-01

The synthesis, characterization and property evaluation of drug-loaded polymer-coated magnetic nanoparticles (MNPs) relevant to multimodal cancer therapy has been studied. The hyperthermia and controlled drug release characteristics of these particles was examined. Magnetite (Fe(3)O(4))-poly-n-(isopropylacrylamide) (PNIPAM) composite MNPs were synthesized in a core-shell morphology by dispersion polymerization of n-(isopropylacrylamide) chains in the presence of a magnetite ferrofluid. These core-shell composite particles, with a core diameter of approximately 13nm, were loaded with the anti-cancer drug doxorubicin (dox), and the resulting composite nanoparticles (CNPs) exhibit thermoresponsive properties. The magnetic properties of the composite particles are close to those of the uncoated magnetic particles. In an alternating magnetic field (AMF), composite particles loaded with 4.15 wt.% dox exhibit excellent heating properties as well as simultaneous drug release. Drug release testing confirmed that release was much higher above the lower critical solution temperature (LCST) of the CNP, with a release of up to 78.1% of bound dox in 29h. Controlled drug release testing of the particles reveals that the thermoresponsive property can act as an on/off switch by blocking drug release below the LCST. Our work suggests that these dox-loaded polymer-coated MNPs show excellent in vitro hyperthermia and drug release behavior, with the ability to release drugs in the presence of AMF, and the potential to act as agents for combined targeting, hyperthermia and controlled drug release treatment of cancer.

Elaboration of nano-structured grafted polymeric surface.

PubMed

Vrlinic, Tjasa; Debarnot, Dominique; Mozetic, Miran; Vesel, Alenka; Kovac, Janez; Coudreuse, Arnaud; Legeay, Gilbert; Poncin-Epaillard, Fabienne

2011-10-15

The surface grafting of multi-polymeric materials can be achieved by grafting as components such as polymers poly(N-isopropylacrylamide) and/or surfactant molecules (hexatrimethylammonium bromide, polyoxyethylene sorbitan monolaurate). The chosen grafting techniques, i.e. plasma activation followed by coating, allow a large spectrum of functional groups that can be inserted on the surface controlling the surface properties like adhesion, wettability and biocompatibility. The grafted polypropylene surfaces were characterized by contact angle analyses, XPS and AFM analyses. The influence of He plasma activation, of the coating parameters such as concentrations of the various reactive agents are discussed in terms of hydrophilic character, chemical composition and morphologic surface heterogeneity. The plasma pre-activation was shown inevitable for a permanent polymeric grafting. PNIPAM was grafted alone or with a mixture of the surfactant molecules. Depending on the individual proportion of each component, the grafted surfaces are shown homogeneous or composed of small domains of one component leading to a nano-structuration of the grafted surface. Copyright © 2011 Elsevier Inc. All rights reserved.

Shear thinning in soft particle suspensions

NASA Astrophysics Data System (ADS)

Voudouris, Panayiotis; van der Zanden, Berco; Florea, Daniel; Fahimi, Zahra; Wyss, Hans

2012-02-01

Suspensions of soft deformable particles are encountered in a wide range of food and biological materials. Examples are biological cells, micelles, vesicles or microgel particles. While the behavior of suspenions of hard spheres - the classical model system of colloid science - is reasonably well understood, a full understanding of these soft particle suspensions remains elusive. The relation between single particle properties and macroscopic mechanical behavior still remains poorly understood in these materials. Here we examine the surprising shear thinning behavior that is observed in soft particle suspensions as a function of particle softness. We use poly-N-isopropylacrylamide (p-NIPAM) microgel particles as a model system to study this effect in detail. These soft spheres show significant shear thinning even at very large Peclet numbers, where this would not be observed for hard particles. The degree of shear thinning is directly related to the single particle elastic properties, which we characterize by the recently developed Capillary Micromechanics technique. We present a simple model that qualitatively accounts for the observed behavior.

Crystal morphology modification by the addition of tailor-made stereocontrolled poly(N-isopropyl acrylamide).

PubMed

Munk, Tommy; Baldursdottir, Stefania; Hietala, Sami; Rades, Thomas; Kapp, Sebastian; Nuopponen, Markus; Kalliomäki, Katriina; Tenhu, Heikki; Rantanen, Jukka

2012-07-02

The use of additives in crystallization of pharmaceuticals is known to influence the particulate properties critically affecting downstream processing and the final product performance. Desired functionality can be build into these materials, e.g. via optimized synthesis of a polymeric additive. One such additive is the thermosensitive polymer poly(N-isopropyl acrylamide) (PNIPAM). The use of PNIPAM as a crystallization additive provides a possibility to affect viscosity at separation temperatures and nucleation and growth rates at higher temperatures. In this study, novel PNIPAM derivatives consisting of both isotactic-rich and atactic blocks were used as additives in evaporative crystallization of a model compound, nitrofurantoin (NF). Special attention was paid to possible interactions between NF and PNIPAM and the aggregation state of PNIPAM as a function of temperature and solvent composition. Optical light microscopy and Raman and FTIR spectroscopy were used to investigate the structure of the NF crystals and possible interaction with PNIPAM. A drastic change in the growth mechanism of nitrofurantoin crystals as monohydrate form II (NFMH-II) was observed in the presence of PNIPAM; the morphology of crystals changed from needle to dendritic shape. Additionally, the amphiphilic nature of PNIPAM increased the solubility of nitrofurantoin in water. PNIPAMs with varying molecular weights and stereoregularities resulted in similar changes in the crystal habit of the drug regardless of whether the polymer was aggregated or not. However, with increased additive concentration slower nucleation and growth rates of the crystals were observed. Heating of the crystallization medium resulted in phase separation of the PNIPAM. The phase separation had an influence on the achieved crystal morphology resulting in fewer, visually larger and more irregular dendritic crystals. No proof of hydrogen bond formation between PNIPAM and NF was observed, and the suggested mechanism for the observed dendritic morphology is related to the steric hindrance phenomenon. PNIPAM can be used as a crystallization additive with an obvious effect on the growth of NF crystals.

Dual responsive PNIPAM-chitosan targeted magnetic nanopolymers for targeted drug delivery

NASA Astrophysics Data System (ADS)

Yadavalli, Tejabhiram; Ramasamy, Shivaraman; Chandrasekaran, Gopalakrishnan; Michael, Isaac; Therese, Helen Annal; Chennakesavulu, Ramasamy

2015-04-01

A dual stimuli sensitive magnetic hyperthermia based drug delivery system has been developed for targeted cancer treatment. Thermosensitive amine terminated poly-N-isopropylacrylamide complexed with pH sensitive chitosan nanoparticles was prepared as the drug carrier. Folic acid and fluorescein were tagged to the nanopolymer complex via N-hydroxysuccinimide and ethyl-3-(3-dimethylaminopropyl)carbodiimide reaction to form a fluorescent and cancer targeting magnetic carrier system. The formation of the polymer complex was confirmed using infrared spectroscopy. Gadolinium doped nickel ferrite nanoparticles prepared by a hydrothermal method were encapsulated in the polymer complex to form a magnetic drug carrier system. The proton relaxation studies on the magnetic carrier system revealed a 200% increase in the T1 proton relaxation rate. These magnetic carriers were loaded with curcumin using solvent evaporation method with a drug loading efficiency of 86%. Drug loaded nanoparticles were tested for their targeting and anticancer properties on four cancer cell lines with the help of MTT assay. The results indicated apoptosis of cancer cell lines within 3 h of incubation.

Effects of fluid shear stress on polyelectrolyte multilayers by neutron scattering studies

DOE PAGES

Singh, Saurabh; Junghans, Ann; Watkins, Erik; ...

2015-02-17

The structure of layer-by-layer (LbL) deposited nanofilm coatings consists of alternating polyethylenimine (PEI) and polystyrenesulfonate (PSS) films deposited on a single crystal quartz substrate. LbL-deposited nanofilms were investigated by neutron reflectomery (NR) in contact with water in the static and fluid shear stress conditions. The fluid shear stress was applied through a laminar flow of the liquid parallel to the quartz/polymer interface in a custom-built solid–liquid interface cell. The scattering length density profiles obtained from NR results of these polyelectrolyte multilayers (PEM), measured under different shear conditions, showed proportional decrease of volume fraction of water hydrating the polymers. For themore » highest shear rate applied (ca. 6800 s –1) the water volume fraction decreased by approximately 7%. The decrease of the volume fraction of water was homogeneous through the thickness of the film. Since there were not any significant changes in the total polymer thickness, it resulted in negative osmotic pressures in the film. The PEM films were compared with the behavior of thin films of thermoresponsive poly(N-isopropylacrylamide) (pNIPAM) deposited via spin-coating. The PEM and pNIPAM differ in their interactions with water molecules, and they showed opposite behaviors under the fluid shear stress. In both cases the polymer hydration was reversible upon the restoration of static conditions. Furthermore, a theoretical explanation is given to explain this difference in the effect of shear on hydration of polymeric thin films.« less

Electrically-receptive and thermally-responsive paper-based sensor chip for rapid detection of bacterial cells.

PubMed

Khan, Muhammad S; Misra, Santosh K; Dighe, Ketan; Wang, Zhen; Schwartz-Duval, Aaron S; Sar, Dinabandhu; Pan, Dipanjan

2018-07-01

Although significant technological advancements have been made in the development of analytical biosensor chips for detecting bacterial strains (E. coli, S. Mutans and B. Subtilis), critical requirements i.e. limit of detection (LOD), fast time of response, ultra-sensitivity with high reproducibility and good shelf-life with robust sensing capability have yet to be met within a single sensor chip. In order to achieve these criteria, we present an electrically-receptive thermally-responsive (ER-TR) sensor chip comprised of simple filter paper used as substrate coated with composite of poly(N-isopropylacrylamide) polymer (PNIPAm) - graphene nanoplatelet (GR) followed by evaporation of Au electrodes for capturing both Gram-positive (S. mutans and B. subtilis) and Gram-negative (E. coli) bacterial cells in real-time. Autoclave water, tap water, lake water and milk samples were tested with ER-TR chip with and without bacterial strains at varying concentration range 10 1 -10 5 cells/mL. The sensor was integrated with in-house built printed circuit board (PCB) to transmit/receive electrical signals. The interaction of E. coli, S. mutans and B. subtilis cells with fibers of PNIPAm-GR resulted in a change of electrical resistance and the readout was monitored wirelessly in real-time using MATLAB algorithm. Finally, prepared ER-TR chip exhibited the reproducibility of 85-97% with shelf-life of up to four weeks after testing with lake water sample. Copyright © 2018 Elsevier B.V. All rights reserved.

From repulsive to attractive glass: A rheological investigation.

PubMed

Zhou, Zhi; Jia, Di; Hollingsworth, Javoris V; Cheng, He; Han, Charles C

2015-12-21

Linear rheological properties and yielding behavior of polystyrene core and poly (N-isopropylacrylamide) (PNIPAM) shell microgels were investigated to understand the transition from repulsive glass (RG) to attractive glass (AG) and the A3 singularity. Due to the volume phase transition of PNIPAM in aqueous solution, the microgel-microgel interaction potential gradually changes from repulsive to attractive. In temperature and frequency sweep experiments, the storage modulus (G') and loss modulus (G″) increased discontinuously when crossing the RG-to-AG transition line, while G' at low frequency exhibited a different volume fraction (Φ) dependence. By fitting the data of RG and AG, and then extrapolating to high volume fraction, the difference between RG and AG decreased and the existence of A3 singularity was verified. Dynamic strain sweep experiments were conducted to confirm these findings. RG at 25 °C exhibited one-step yielding, whereas AG at 40 °C showed a typical two-step yielding behavior; the first yielding strain remained constant and the second one gradually decreased as the volume fraction increased. By extrapolating the second yield strain to that of the first one, the predicted A3 singularity was at 0.61 ± 0.02. At 37 °C, when Φeff = 0.59, AG showed one step yielding as the length of the attractive bond increased. The consistency and agreement of the experimental results reaffirmed the existence of A3 singularity, where the yielding behavior of RG and AG became identical.

Ternary polyplex micelles with PEG shells and intermediate barrier to complexed DNA cores for efficient systemic gene delivery.

PubMed

Li, Junjie; Chen, Qixian; Zha, Zengshi; Li, Hui; Toh, Kazuko; Dirisala, Anjaneyulu; Matsumoto, Yu; Osada, Kensuke; Kataoka, Kazunori; Ge, Zhishen

2015-07-10

Simultaneous achievement of prolonged retention in blood circulation and efficient gene transfection activity in target tissues has always been a major challenge hindering in vivo applications of nonviral gene vectors via systemic administration. Herein, we constructed novel rod-shaped ternary polyplex micelles (TPMs) via complexation between the mixed block copolymers of poly(ethylene glycol)-b-poly{N'-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} (PEG-b-PAsp(DET)) and poly(N-isopropylacrylamide)-b-PAsp(DET) (PNIPAM-b-PAsp(DET)) and plasmid DNA (pDNA) at room temperature, exhibiting distinct temperature-responsive formation of a hydrophobic intermediate layer between PEG shells and pDNA cores through facile temperature increase from room temperature to body temperature (~37 °C). As compared with binary polyplex micelles of PEG-b-PAsp(DET) (BPMs), TPMs were confirmed to condense pDNA into a more compact structure, which achieved enhanced tolerability to nuclease digestion and strong counter polyanion exchange. In vitro gene transfection results demonstrated TPMs exhibiting enhanced gene transfection efficiency due to efficient cellular uptake and endosomal escape. Moreover, in vivo performance evaluation after intravenous injection confirmed that TPMs achieved significantly prolonged blood circulation, high tumor accumulation, and promoted gene expression in tumor tissue. Moreover, TPMs loading therapeutic pDNA encoding an anti-angiogenic protein remarkably suppressed tumor growth following intravenous injection into H22 tumor-bearing mice. These results suggest TPMs with PEG shells and facilely engineered intermediate barrier to inner complexed pDNA have great potentials as systemic nonviral gene vectors for cancer gene therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

New Linear and Star-Shaped Thermogelling Poly([R]-3-hydroxybutyrate) Copolymers.

PubMed

Barouti, Ghislaine; Liow, Sing Shy; Dou, Qingqing; Ye, Hongye; Orione, Clément; Guillaume, Sophie M; Loh, Xian Jun

2016-07-18

The synthesis of multi-arm poly([R]-3-hydroxybutyrate) (PHB)-based triblock copolymers (poly([R]-3-hydroxybutyrate)-b-poly(N-isopropylacrylamide)-b-[[poly(methyl ether methacrylate)-g-poly(ethylene glycol)]-co-[poly(methacrylate)-g-poly(propylene glycol)

Synthesis and characterization of a poly(lactic-co-glycolic acid) core + poly(N-isopropylacrylamide) shell nanoparticle system

PubMed Central

Kosinski, Aaron M.; Brugnano, Jamie L.; Seal, Brandon L.; Knight, Frances C.; Panitch, Alyssa

2012-01-01

Poly(lactic-co-glycolic acid) (PLGA) is a popular material used to prepare nanoparticles for drug delivery. However, PLGA nanoparticles lack desirable attributes including active targeting abilities, resistance to aggregation during lyophilization, and the ability to respond to dynamic environmental stimuli. To overcome these issues, we fabricated a nanoparticle consisting of a PLGA core encapsulated within a shell of poly(N-isopropylacrylamide). Dynamic light scattering and transmission electron microscope imaging were used to characterize the nanoparticles, while an MTT assay and ELISA suggested biocompatibility in THP1 cells. Finally, a collagen type II binding assay showed successful modification of these nanoparticles with an active targeting moiety. PMID:23507885

Fabricating Degradable Thermoresponsive Hydrogels on Multiple Length Scales via Reactive Extrusion, Microfluidics, Self-assembly, and Electrospinning.

PubMed

Sivakumaran, Daryl; Bakaic, Emilia; Campbell, Scott B; Xu, Fei; Mueller, Eva; Hoare, Todd

2018-04-16

While various smart materials have been explored for a variety of biomedical applications (e.g., drug delivery, tissue engineering, bioimaging, etc.), their ultimate clinical use has been hampered by the lack of biologically-relevant degradation observed for most smart materials. This is particularly true for temperature-responsive hydrogels, which are almost uniformly based on polymers that are functionally non-degradable (e.g., poly(N-isopropylacrylamide) (PNIPAM) or poly(oligoethylene glycol methacrylate) (POEGMA)). As such, to effectively translate the potential of thermoresponsive hydrogels to the challenges of remote-controlled or metabolism-regulated drug delivery, cell scaffolds with tunable cell-material interactions, theranostic materials with the potential for both imaging and drug delivery, and other such applications, a method is required to render the hydrogels (if not fully degradable) at least capable of renal clearance following the required lifetime of the material. To that end, this protocol describes the preparation of hydrolytically-degradable hydrazone-crosslinked hydrogels on multiple length scales based on the reaction between hydrazide and aldehyde-functionalized PNIPAM or POEGMA oligomers with molecular weights below the renal filtration limit. Specifically, methods to fabricate degradable thermoresponsive bulk hydrogels (using a double barrel syringe technique), hydrogel particles (on both the microscale through the use of a microfluidics platform facilitating simultaneous mixing and emulsification of the precursor polymers and the nanoscale through the use of a thermally-driven self-assembly and cross-linking method), and hydrogel nanofibers (using a reactive electrospinning strategy) are described. In each case, hydrogels with temperature-responsive properties similar to those achieved via conventional free radical cross-linking processes can be achieved, but the hydrazone cross-linked network can be degraded over time to re-form the oligomeric precursor polymers and enable clearance. As such, we anticipate these methods (which may be generically applied to any synthetic water-soluble polymer, not just smart materials) will enable easier translation of synthetic smart materials to clinical applications.

Particles decorated by an ionizable thermoresponsive polymer brush in water: experiments and self-consistent field modeling.

PubMed

Alves, S P C; Pinheiro, J P; Farinha, J P S; Leermakers, F A M

2014-03-20

We have synthesized anionic multistimuli responsive core-shell polymer nanoparticles with low size dispersity composed of glassy poly(methyl methacrylate) (PMMA) cores of ca. 40 nm radius and poly(N-isopropylacrylamide) (PNIPAM) anionic brush-like shells with methacrylic acid comonomers. Using dynamic light scattering, we observed a volume phase transition upon an increase in temperature and this response was pH and ionic strength dependent. Already at room temperature we observed a pronounced polyelectrolyte effect, that is, a shift of the apparent pKa extracted from the degree of dissociation of the acids as a function of the pH. The multiresponsive behavior of the hydrophobic polyelectrolyte brush has been modeled using the Scheutjens-Fleer self-consistent field (SF-SCF) approach. Using a phenomenological relation between the Flory-Huggins χ parameter and the temperature, we confront the predicted change in the brush height with the observed change of the hydrodynamic radius and degree of dissociation and obtain estimates for the average chain lengths (number of Kuhn segments) of the corona chains, the grafting density and charge density distributions. The theory reveals a rich internal structure of the hydrophobic polyelectrolyte brush, especially near the collapse transition, where we find a microphase segregated structure. Considering this complexity, it is fair to state that the theoretical predictions follow the experimental data semiquantitatively, and it is attractive to attribute the observed disparity between theory and experiments to the unknown polydispersity of the chains, the unknown distribution of the charges, or other experimental complications. More likely, however, the deviations point to significant problems of the mean field theory, which focuses solely on the radial distributions and ignores the possibility of the formation of lateral (local) inhomogeneities in partially collapsed polyelectrolyte brushes. We argue that the PNIPAM brush at room temperature is already behaving nonideally.

A thermoresponsive nanorattle containing two different catalysts for controllable one-pot tandem catalysis

NASA Astrophysics Data System (ADS)

Niu, Chengrong; Hu, Jie; Li, Yinfeng; Leng, Jinghang; Li, Songjun

2018-03-01

In the present work, a thermoresponsive nanorattle with a Ag nanoparticle (NP) core (one catalyst in the nanorattle), and a poly(N-isopropylacrylamide) shell was developed. An imidazole group was grafted on the polymer shell by copolymerization as the other catalyst. Owing to the catalytic activities of the imidazole group and Ag NP with regards to hydrolysis and reduction, respectively, this nanorattle exhibited tandem-reaction catalytic abilities. In addition, because of the shrinkage of the poly(N-isopropylacrylamide) shell at high temperatures, the tandem reaction could be controlled to stop at the first reaction step. That is to say, only the hydrolysis reaction was catalyzed by the imidazole group being grafted on the surface of the shell. The reduction step in the tandem reaction catalyzed by the Ag particle, however, was switched off by the shrinkage of the poly(N-isopropylacrylamide) shell. This protocol opens up an opportunity to develop controllable catalysts for complicated chemical processes.

Photothermal Nanocomposite Hydrogel Actuator with Electric-Field-Induced Gradient and Oriented Structure.

PubMed

Yang, Yang; Tan, Yun; Wang, Xionglei; An, Wenli; Xu, Shimei; Liao, Wang; Wang, Yuzhong

2018-03-07

Recent research of hydrogel actuators is still not sophisticated enough to meet the requirement of fast, reversible, complex, and robust reconfiguration. Here, we present a new kind of poly( N-isopropylacrylamide)/graphene oxide gradient hydrogel by utilizing direct current electric field to induce gradient and oriented distribution of graphene oxide into poly( N-isopropylacrylamide) hydrogel. Upon near-infrared light irradiation, the hydrogel exhibited excellent comprehensive actuation performance as a result of directional bending deformation, promising great potential in the application of soft actuators and optomechanical system.

Preparation of Thermo-Responsive and Cross-Linked Fluorinated Nanoparticles via RAFT-Mediated Aqueous Polymerization in Nanoreactors.

PubMed

Ma, Jiachen; Zhang, Luqing; Geng, Bing; Azhar, Umair; Xu, Anhou; Zhang, Shuxiang

2017-01-25

In this work, a thermo-responsive and cross-linked fluoropolymer poly(2,2,2-Trifluoroethyl) methacrylate (PTFEMA) was successfully prepared by reversible addition-fragmentation chain transfer (RAFT) mediated aqueous polymerization with a thermo-responsive diblock poly(dimethylacrylamide- b - N -isopropylacrylamide) (PDMA- b -PNIPAM) that performed a dual function as both a nanoreactor and macro-RAFT agent. The cross-linked polymer particles proved to be in a spherical-like structure of about 50 nm in diameter and with a relatively narrow particle size distribution. ¹H-NMR and 19 F-NMR spectra showed that thermo-responsive diblock P(DMA- b -NIPAM) and cross-linked PTFEMA particles were successfully synthesized. Influence of the amount of ammonium persulfate (APS), the molar ratio of monomers to RAFT agent, influence of the amount of cross-linker on aqueous polymerization and thermo-responsive characterization of the particles are investigated. Monomer conversion increased from 44% to 94% with increasing the molar ratio of APS and P(DMA- b -NIPAM) from 1:9 to1:3. As the reaction proceeded, the particle size increased from 29 to 49 nm due to the consumption of TFEMA monomer. The size of cross-linked nanoparticles sharply decreased from 50.3 to 40.5 nm over the temperature range 14-44 °C, suggesting good temperature sensitivity for these nanoparticles.

Mesoscopic simulation of a micellar poly(N-isopropyl acrylamide)-b-(polyethylene oxide) copolymer system

NASA Astrophysics Data System (ADS)

Bautista-Reyes, Rubén; Soto-Figueroa, César; Vicente, Luis

2016-05-01

In this article we studied the micellar formation of poly(N-isopropyl acrylamide)-b-polyethylene oxide (PNIPAM-b-PEO) copolymers in an aqueous system. From molecular simulations the dependence on temperature of the Flory-Huggins interaction parameter χ for PNIPAM and PEO in water is obtained and compared with available experimental results and values from other theoretical calculations. By means of dissipative particle dynamics (DPD) we then simulated the coil-globule transition for PNIPAM chains in water with a transition temperature of around 305 K. The simulations for PNIPAM-b-PEO copolymers showed that at room temperature the chains are miscible in an aqueous phase but with a temperature increase the system turns into micelles at T  =  305 K. The change in micelle anisotropy due to a different ratio PNIPAM/PEO of chains is also analyzed. What is observed is that for large PEO the large number of dissolved PEO chains gives a large corona size and the micelle is not spherical but obloide and as the number of PNIPAM is increased the micelle acquires a spherical shape. As an important application we considered the system micelle-water/anionic liquid (1-butyl-3-methylimidazolium hexafluorophosphate [BMIM]+[PF6]-). By increasing the temperature of the system from 306 K it is shown that at T  =  345 K there is a transfer of the micelle from water to the ionic liquid phase and this was due to the change in the relative affinity of PEO to water and ionic liquid expressed by the change in χ. All the simulation outcomes are qualitatively consistent with experimental results and thus to our knowledge we give the first set of χ values for the interaction between PNIPAM and water in a wide range of temperature values.

Synthesis of sharply thermo and PH responsive PMA-b-PNIPAM-b-PEG-b-PNIPAM-b-PMA by RAFT radical polymerization and its schizophrenic micellization in aqueous solutions.

PubMed

Ahmadkhani, Lida; Abbasian, Mojtaba; Akbarzadeh, Abolfazl

2017-01-01

Sharply thermo- and pH-responsive pentablock terpolymer with a core-shell-corona structure was prepared by RAFT polymerization of N-isopropylacrylamide and methacrylic acid monomers using PEG-based benzoate-type of RAFT agent. The PEG-based RAFT agent could be easily synthesized by dihydroxyl-capped PEG with 4-cyano-4-(thiobenzoyl) sulfanylpentanoic acids, using esterification reaction. This pentablock terpolymer was characterized by 1 H NMR, FT-IR, and GPC. The PDI was obtained by GPC, indicating that the molecular weight distribution was narrow and the polymerization was well controlled. The thermo- and pH-responsive micellization of the pentablock terpolymer in aqueous solution was investigated using fluorescence spectroscopy technique, UV-vis transmittance, and TEM. The LCST of pentablock terpolymer increased (over 50 °C) compared to the NIPAM homopolymer (~32 °C), due to the incorporation of the hydrophilic PEG and PMA blocks in pentablock terpolymer (PNIPAM block as the core, PEG the block and the hydrophilic PMA block as the shell and the corona). Also, pH-dependent phase transition behavior shows at a pH value of about ~5.8, according to pKa of MAA. Thus, in acidic solution at room temperature, the pentablock terpolymer self-assembled to form core-shell-corona micelles, with the hydrophobic PMA block as the core, the PNIPAM block and the hydrophilic PEG block as the shell and the corona, respectively.

Phase Transition of Poly(acrylic acid-co-N-isopropylacrylamide) Core-shell Nanogels

NASA Astrophysics Data System (ADS)

Liu, Xiao-bing; Zhou, Jian-feng; Ye, Xiao-dong

2012-08-01

A series of poly(acrylic acid) macromolecular chain transfer agents with different molecular weights were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization and characterized by 1H NMR and gel permeation chromatography. Multiresponsive core-shell nanogels were prepared by dispersion polymerization of N-isopropylacrylamide in water using these poly(potassium acrylate) macro-RAFT agents as the electrosteric stabilizer. The size of the nanogels decreases with the amount of the macro-RAFT agent, indicating that the surface area occupied by per polyelectrolyte group is a critical parameter for stabilizing the nanogels. The volume phase transition and the zeta potentials of the nanogels in aqueous solutions were studied by dynamic light scattering and zetasizer analyzer, respectively.

Remotely Triggered Scaffolds for Controlled Release of Pharmaceuticals

PubMed Central

Roach, Paul; McGarvey, David J.; Lees, Martin R.; Hoskins, Clare

2013-01-01

Fe3O4-Au hybrid nanoparticles (HNPs) have shown increasing potential for biomedical applications such as image guided stimuli responsive drug delivery. Incorporation of the unique properties of HNPs into thermally responsive scaffolds holds great potential for future biomedical applications. Here we successfully fabricated smart scaffolds based on thermo-responsive poly(N-isopropylacrylamide) (pNiPAM). Nanoparticles providing localized trigger of heating when irradiated with a short laser burst were found to give rise to remote control of bulk polymer shrinkage. Gold-coated iron oxide nanoparticles were synthesized using wet chemical precipitation methods followed by electrochemical coating. After subsequent functionalization of particles with allyl methyl sulfide, mercaptodecane, cysteamine and poly(ethylene glycol) thiol to enhance stability, detailed biological safety was determined using live/dead staining and cell membrane integrity studies through lactate dehydrogenase (LDH) quantification. The PEG coated HNPs did not show significant cytotoxic effect or adverse cellular response on exposure to 7F2 cells (p < 0.05) and were carried forward for scaffold incorporation. The pNiPAM-HNP composite scaffolds were investigated for their potential as thermally triggered systems using a Q-switched Nd:YAG laser. These studies show that incorporation of HNPs resulted in scaffold deformation after very short irradiation times (seconds) due to internal structural heating. Our data highlights the potential of these hybrid-scaffold constructs for exploitation in drug delivery, using methylene blue as a model drug being released during remote structural change of the scaffold. PMID:23603890

1H NMR investigation of thermally triggered insulin release from poly(N-isopropylacrylamide) microgels.

PubMed

Nolan, Christine M; Gelbaum, Leslie T; Lyon, L Andrew

2006-10-01

We describe investigations of insulin release from thermoresponsive microgels using variable temperature (1)H NMR. Microgel particles composed of poly(N-isopropylacrylamide) were loaded with the peptide via a swelling technique, and this method was compared to simple equilibrium partitioning. Variable temperature (1)H NMR studies suggest that the swelling loading method results in enhanced entrapment of the peptide versus equilibrium partitioning. A centrifugation-loading assay supports this finding. Pseudo-temperature jump (1)H NMR measurements suggest that the insulin release rate is partially decoupled from microgel collapse. These types of direct release investigations could prove to be useful methods in the future design of controlled macromolecule drug delivery devices.

Synthesis and evaluation on pH- and temperature-responsive chitosan-p(MAA-co-NIPAM) hydrogels.

PubMed

Rasib, S Z M; Ahmad, Z; Khan, A; Akil, H M; Othman, M B H; Hamid, Z A A; Ullah, F

2018-03-01

In this study, chitosan-poly(methacrylic acid-co-N-isopropylacrylamide) [chitosan-p(MAA-co-NIPAM)] hydrogels were synthesized by emulsion polymerization. In order to be used as a carrier for drug delivery systems, the hydrogels had to be biocompatible, biodegradable and multi-responsive. The polymerization was performed by copolymerize MAA and NIPAM with chitosan polymer to produce a chitosan-based hydrogel. Due to instability during synthesis and complexity of components to produce the hydrogel, further study at different times of reaction is important to observe the synthesis process, the effect of end product on swelling behaviour and the most important is to find the best way to control the hydrogel synthesis in order to have an optimal swelling behaviour for drug release application. Studied by using Fourier transform infra-red (FTIR) spectroscopy found that, the synthesized was successfully produced stable chitosan-based hydrogel with PNIPAM continuously covered the outer surface of hydrogel which influenced much on the stability during synthesis. The chitosan and PMAA increased the zeta potential of the hydrogel and the chitosan capable to control shrinkage above human body temperature. The chitosan-p(MAA-co-NIPAM) hydrogels also responses to pH and temperature thus improved the ability to performance as a drug carrier. Copyright © 2017 Elsevier B.V. All rights reserved.

Synergistically enhanced selective intracellular uptake of anticancer drug carrier comprising folic acid-conjugated hydrogels containing magnetite nanoparticles

NASA Astrophysics Data System (ADS)

Kim, Haneul; Jo, Ara; Baek, Seulgi; Lim, Daeun; Park, Soon-Yong; Cho, Soo Kyung; Chung, Jin Woong; Yoon, Jinhwan

2017-01-01

Targeted drug delivery has long been extensively researched since drug delivery and release at the diseased site with minimum dosage realizes the effective therapy without adverse side effects. In this work, to achieve enhanced intracellular uptake of anticancer drug carriers for efficient chemo-therapy, we have designed targeted multifunctional anticancer drug carrier hydrogels. Temperature-responsive poly(N-isopropylacrylamide) (PNIPAm) hydrogel core containing superparamagnetic magnetite nanoparticles (MNP) were prepared using precipitation polymerization, and further polymerized with amine-functionalized copolymer shell to facilitate the conjugation of targeting ligand. Then, folic acid, specific targeting ligand for cervical cancer cell line (HeLa), was conjugated on the hydrogel surface, yielding the ligand conjugated hybrid hydrogels. We revealed that enhanced intracellular uptake by HeLa cells in vitro was enabled by both magnetic attraction and receptor-mediated endocytosis, which were contributed by MNP and folic acid, respectively. Furthermore, site-specific uptake of the developed carrier was confirmed by incubating with several other cell lines. Based on synergistically enhanced intracellular uptake, efficient cytotoxicity and apoptotic activity of HeLa cells incubated with anticancer drug loaded hybrid hydrogels were successfully achieved. The developed dual-targeted hybrid hydrogels are expected to provide a platform for the next generation intelligent drug delivery systems.

Novel heavy-metal adsorption material: ion-recognition P(NIPAM-co-BCAm) hydrogels for removal of lead(II) ions.

PubMed

Ju, Xiao-Jie; Zhang, Shi-Bo; Zhou, Ming-Yu; Xie, Rui; Yang, Lihua; Chu, Liang-Yin

2009-08-15

A novel polymeric lead(II) adsorbent is prepared by incorporating benzo-18-crown-6-acrylamide (BCAm) as metal ion receptor into the thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) hydrogel. Both stimuli-sensitive properties and the Pb(2+)-adsorption capabilities of the prepared P(NIPAM-co-BCAm) hydrogels are investigated. The prepared P(NIPAM-co-BCAm) hydrogels exhibit good ion-recognition and Pb(2+)-adsorption characteristics. When crown ether units capture Pb(2+) and form BCAm/Pb(2+) host-guest complexes, the lower critical solution temperature (LCST) of the hydrogel shifts to a higher temperature due to both the repulsion among charged BCAm/Pb(2+) groups and the osmotic pressure within the hydrogel. The adsorption results at different temperatures show that P(NIPAM-co-BCAm) hydrogels adsorb Pb(2+) ions at temperature lower than the LCST, but undergo desorption at temperature higher than the LCST due to the "stretch-to-shrink" configuration change of copolymer networks which is triggered by the change in environmental temperature. This kind of ion-recognition hydrogel is promising as a novel adsorption material for adsorption and separation of Pb(2+) ions. The adsorption and desorption of Pb(2+) could be rationally achieved by simply changing the environmental temperature.

Reversible Self-Actuated Thermo-Responsive Pore Membrane

PubMed Central

Park, Younggeun; Gutierrez, Maria Paz; Lee, Luke P.

2016-01-01

Smart membranes, which can selectively control the transfer of light, air, humidity and temperature, are important to achieve indoor climate regulation. Even though reversible self-actuation of smart membranes is desirable in large-scale, reversible self-regulation remains challenging. Specifically, reversible 100% opening/closing of pore actuation showing accurate responsiveness, reproducibility and structural flexibility, including uniform structure assembly, is currently very difficult. Here, we report a reversible, thermo-responsive self-activated pore membrane that achieves opening and closing of pores. The reversible, self-actuated thermo-responsive pore membrane was fabricated with hybrid materials of poly (N-isopropylacrylamide), (PNIPAM) within polytetrafluoroethylene (PTFE) to form a multi-dimensional pore array. Using Multiphysics simulation of heat transfer and structural mechanics based on finite element analysis, we demonstrated that pore opening and closing dynamics can be self-activated at environmentally relevant temperatures. Temperature cycle characterizations of the pore structure revealed 100% opening ratio at T = 40 °C and 0% opening ratio at T = 20 °C. The flexibility of the membrane showed an accurate temperature-responsive function at a maximum bending angle of 45°. Addressing the importance of self-regulation, this reversible self-actuated thermo-responsive pore membrane will advance the development of future large-scale smart membranes needed for sustainable indoor climate control. PMID:27991563

Thermodynamic description of Hofmeister effects on the LCST of thermosensitive polymers.

PubMed

Heyda, Jan; Dzubiella, Joachim

2014-09-18

Cosolvent effects on protein or polymer collapse transitions are typically discussed in terms of a two-state free energy change that is strictly linear in cosolute concentration. Here we investigate in detail the nonlinear thermodynamic changes of the collapse transition occurring at the lower critical solution temperature (LCST) of the role-model polymer poly(N-isopropylacrylamide) [PNIPAM] induced by Hofmeister salts. First, we establish an equation, based on the second-order expansion of the two-state free energy in concentration and temperature space, which excellently fits the experimental LCST curves and enables us to directly extract the corresponding thermodynamic parameters. Linear free energy changes, grounded on generic excluded-volume mechanisms, are indeed found for strongly hydrated kosmotropes. In contrast, for weakly hydrated chaotropes, we find significant nonlinear changes related to higher order thermodynamic derivatives of the preferential interaction parameter between salts and polymer. The observed non-monotonic behavior of the LCST can then be understood from a not yet recognized sign change of the preferential interaction parameter with salt concentration. Finally, we find that solute partitioning models can possibly predict the linear free energy changes for the kosmotropes, but fail for chaotropes. Our findings cast strong doubt on their general applicability to protein unfolding transitions induced by chaotropes.

Reversible Self-Actuated Thermo-Responsive Pore Membrane

NASA Astrophysics Data System (ADS)

Park, Younggeun; Gutierrez, Maria Paz; Lee, Luke P.

2016-12-01

Smart membranes, which can selectively control the transfer of light, air, humidity and temperature, are important to achieve indoor climate regulation. Even though reversible self-actuation of smart membranes is desirable in large-scale, reversible self-regulation remains challenging. Specifically, reversible 100% opening/closing of pore actuation showing accurate responsiveness, reproducibility and structural flexibility, including uniform structure assembly, is currently very difficult. Here, we report a reversible, thermo-responsive self-activated pore membrane that achieves opening and closing of pores. The reversible, self-actuated thermo-responsive pore membrane was fabricated with hybrid materials of poly (N-isopropylacrylamide), (PNIPAM) within polytetrafluoroethylene (PTFE) to form a multi-dimensional pore array. Using Multiphysics simulation of heat transfer and structural mechanics based on finite element analysis, we demonstrated that pore opening and closing dynamics can be self-activated at environmentally relevant temperatures. Temperature cycle characterizations of the pore structure revealed 100% opening ratio at T = 40 °C and 0% opening ratio at T = 20 °C. The flexibility of the membrane showed an accurate temperature-responsive function at a maximum bending angle of 45°. Addressing the importance of self-regulation, this reversible self-actuated thermo-responsive pore membrane will advance the development of future large-scale smart membranes needed for sustainable indoor climate control.

Design of poly(vinylidene fluoride)-g-p(hydroxyethyl methacrylate-co-N-isopropylacrylamide) membrane via surface modification for enhanced fouling resistance and release property

NASA Astrophysics Data System (ADS)

Zhao, Guili; Chen, Wei Ning

2017-03-01

Thermo-sensitive polymer poly(N-isopropylacrylamide) (PNIPAAm), hydrophilic polymer poly(hydroxyethyl methacrylate) (PHEMA) and copolymer p(hydroxyethyl methacrylate-co-N-isopropylacrylamide) [P(HEMA-co-NIPAAm)] were synthesized onto poly(vinylidene fluoride) (PVDF) membrane via atom transfer radical polymerization (ATRP) in order to improve not only fouling resistance but also fouling release property. The physicochemical properties of membranes including hydrophilicity, morphology and roughness were examined by contact angle analyzer, scanning electron microscopy (SEM), and atomic force microscopy (AFM), respectively. The antifouling property of membranes was improved remarkably after surface modification according to protein and bacterial adhesion testing, and filtration experiment. Minimum protein adsorption and bacterial adhesion were both obtained on PVDF-g-P(HEMA-co-NIPAAm) membrane, with reduction by 44% and 71% respectively compared to the pristine membrane. The minimum bacterial cells after detachment at 25 °C were observed on the PVDF-g-P(HEMA-co-NIPAAm) membrane with the detachment rate of 77%, indicating high fouling release property. The filtration testing indicated that the copolymer modified membrane exhibited high resistance to protein fouling and the foulant on the surface was released and removed easily by washing, suggesting high fouling release and easy-cleaning capacity. This study provides useful insight in the combined "fouling resistance" and "fouling release" property of P(HEMA-co-NIPAAm) for PVDF membrane modification, even for other types of the membrane in wide application.

Thermo- and electro-dual responsive poly(ionic liquid) electrolyte based smart windows.

PubMed

Chen, Fei; Ren, Yongyuan; Guo, Jiangna; Yan, Feng

2017-01-31

Thermo- and electro-dual responsive poly(ionic liquid) (PIL) based electrolytes were synthesized by co-polymerization of N-isopropylacrylamide (NIPAM) with (or without) 3-butyl-1-vinyl-imidazolium bromide ([BVIm][Br]) using diallyl-viologen (DAV) as both the cross-linking agent and electrochromic material.

FCC-HCP coexistence in dense thermo-responsive microgel crystals

NASA Astrophysics Data System (ADS)

Karthickeyan, D.; Joshi, R. G.; Tata, B. V. R.

2017-06-01

Analogous to hard-sphere suspensions, monodisperse thermo-responsive poly (N-isopropyl acrylamide) (PNIPAM) microgel particles beyond a volume fraction (ϕ) of 0.5 freeze into face centered cubic (FCC)-hexagonal close packed (HCP) coexistence under as prepared conditions and into an FCC structure upon annealing. We report here FCC-HCP coexistence to be stable in dense PNIPAM microgel crystals (ϕ > 0.74) with particles in their deswollen state (referred to as osmotically compressed microgel crystals) and the FCC structure with particles in their swollen state by performing annealing studies with different cooling rates. The structure of PNIPAM microgel crystals is characterized using static light scattering technique and UV-Visible spectroscopy and dynamics by dynamic light scattering (DLS). DLS studies reveal that the particle motion is diffusive at short times in crystals with ϕ < 0.74 and sub-diffusive at short times in PNIPAM crystals with ϕ > 0.74. The observed sub-diffusive behavior at short times is due to the overlap (interpenetration) of the dangling polymer chains between the shells of neighbouring PNIPAM microgel particles. Overlap is found to disappear upon heating the crystals well above their melting temperature, Tm due to reduction in the particle size. Annealing studies confirm that the overlap of dangling polymer chains between the shells of neighbouring PNIPAM spheres is responsible for the stability of FCC-HCP coexistence observed in osmotically compressed PNIPAM microgel crystals. Results are discussed in the light of recent reports of stabilizing the HCP structure in hard sphere crystals by adding interacting polymer chains.

Buffers more than buffering agent: introducing a new class of stabilizers for the protein BSA.

PubMed

Gupta, Bhupender S; Taha, Mohamed; Lee, Ming-Jer

2015-01-14

In this study, we have analyzed the influence of four biological buffers on the thermal stability of bovine serum albumin (BSA) using dynamic light scattering (DLS). The investigated buffers include 4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid (HEPES), 4-(2-hydroxyethyl)-1-piperazine-propanesulfonic acid (EPPS), 4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid sodium salt (HEPES-Na), and 4-morpholinepropanesulfonic acid sodium salt (MOPS-Na). These buffers behave as a potential stabilizer for the native structure of BSA against thermal denaturation. The stabilization tendency follows the order of MOPS-Na > HEPES-Na > HEPES ≫ EPPS. To obtain an insight into the role of hydration layers and peptide backbone in the stabilization of BSA by these buffers, we have also explored the phase transition of a thermoresponsive polymer, poly(N-isopropylacrylamide (PNIPAM)), a model compound for protein, in aqueous solutions of HEPES, EPPS, HEPES-Na, and MOPS-Na buffers at different concentrations. It was found that the lower critical solution temperatures (LCST) of PNIPAM in the aqueous buffer solutions substantially decrease with increase in buffer concentration. The mechanism of interactions between these buffers and protein BSA was probed by various techniques, including UV-visible, fluorescence, and FTIR. The results of this series of studies reveal that the interactions are mainly governed by the influence of the buffers on the hydration layers surrounding the protein. We have also explored the possible binding sites of BSA with these buffers using a molecular docking technique. Moreover, the activities of an industrially important enzyme α-chymotrypsin (α-CT) in 0.05 M, 0.5 M, and 1.0 M of HEPES, EPPS, HEPES-Na, and MOPS-Na buffer solutions were analyzed at pH = 8.0 and T = 25 °C. Interestingly, the activities of α-CT were found to be enhanced in the aqueous solutions of these investigated buffers. Based upon the Jones-Dole viscosity parameters, the kosmotropic or chaotropic behaviors of the investigated buffers at 25 °C have been examined.

Temperature sensitive poly[N-isopropylacrylamide-co-(acryloyl beta-cyclodextrin)] for improved drug release.

PubMed

Zhang, Jian-Tao; Huang, Shi-Wen; Liu, Ji; Zhuo, Ren-Xi

2005-03-15

The model drugs ibuprofen (IBU) and tegafur (T-Fu) were loaded into poly[N-isopropylacrylamide-co-(acryloyl beta-cyclodextrin)] [P(NIPA-co-A-CD)] and PNIPA hydrogels by immersing dried gels in IBU or T-Fu alcohol solutions until they reached equilibrium. Drug release studies were carried out in water at 25 degrees C. In contrast to the release time of conventional PNIPA hydrogel, that of IBU from the beta-CD incorporated hydrogel was significantly prolonged and the drug loading was also greatly increased, which may be the result of the formation of inclusion complexes between CD and ibuprofen. However, another hydrophilic drug, tegafur, did not display these properties because it could not form a complex with the CD groups. [diagram in text].

Reversible clustering of pH- and temperature-responsive Janus magnetic nanoparticles.

PubMed

Isojima, Tatsushi; Lattuada, Marco; Vander Sande, John B; Hatton, T Alan

2008-09-23

Janus nanoparticles have been synthesized consisting of approximately 5 nm magnetite nanoparticles coated on one side with a pH-dependent and temperature-independent polymer (poly(acrylic acid), PAA), and functionalized on the other side by a second (tail) polymer that is either a pH-independent polymer (polystyrene sodium sulfonate, PSSNa) or a temperature-dependent polymer (poly(N-isopropyl acrylamide), PNIPAM). These Janus nanoparticles are dispersed stably as individual particles at high pH values and low temperatures, but can self-assemble at low pH values (PSSNa) or at high temperatures (>31 degrees C) (PNIPAM) to form stable dispersions of clusters of approximately 80-100 nm in hydrodynamic diameter. The Janus nanoparticle compositions were verified using FTIR and XPS, and their structures observed directly by TEM. Their clustering behavior is analyzed by dynamic light scattering and zeta potential measurements.

Preparation of fast response superabsorbent hydrogels by radiation polymerization and crosslinking of N-isopropylacrylamide in solution

NASA Astrophysics Data System (ADS)

Abd El-Mohdy, H. L.; Safrany, Agnes

2008-03-01

Macroporous temperature-responsive poly( N-isopropylacrylamide) (PNIPAAm) hydrogels with high equilibrium swelling and fast response rates were obtained by a 60Co γ- and electron beam (EB) irradiation of aqueous N-isopropylacrylamide (NIPAAm) monomer solutions. The effect of irradiation temperatures, the dose, the addition of a pore-forming agent on the swelling ratio, and the kinetics of swelling and shrinking of the PNIPAAm gels was studied. The gels synthesized above the LCST exhibited the highest equilibrium swelling (300-400) and fastest response rate measured by minutes. Scanning electron microscope (SEM) pictures revealed that the gels synthesized above the LCST have larger pores than those prepared at temperatures below the LCST. The gels showed a reversible response to cyclical changes in temperature and might be used in a pulsed drug delivery device. The gels synthesized above the LCST exhibited the highest testosterone propionate release.

In situ sum-frequency generation spectroscopy of ethylene-glycol and poly-N-isopropylacrylamide films

NASA Astrophysics Data System (ADS)

Kurz, Volker; Koelsch, Patrick

2009-03-01

Ethylene-glycol(EG)-based self-assembled monolayers (SAMs) are often used as a model systems for thin liquid films. Temperature series in heavy water were measured using a unique sample cell developed for in situ sum-frequency generation (SFG) spectroscopy experiments. Results obtained from model EG-SAMs with different lengths and terminating groups in various ionic solutions showed temperature-dependent changes in the molecular order. Films of poly-N-isopropylacrylamide(pNIPAM) were also characterized by in situ SFG spectroscopy in the CH, OH, OD and amide spectral regions under different polarization combinations. These systems have many applications as thermo-responsive polymers due to their ability to change solubility in water at the biologically relevant temperature of 32 C. This so-called lower critical solution temperature (LCST) phase transition was characterized in depth, allowing for the identification of the molecular groups involved in this process.

Cell engineering: nanometric grafting of poly-N-isopropylacrylamide onto polystyrene film by different doses of gamma radiation

PubMed Central

Biazar, Esmaeil; Zeinali, Reza; Montazeri, Naser; Pourshamsian, Khalil; Behrouz, Mahmoud Jabarvand; Asefnejad, Azadeh; Khoshzaban, Ahad; Shahhosseini, Gholamreza; Najafabadi, Mostafa Soleimannejad; Abyani, Reza; Jamalzadeh, Hamidreza; Fouladi, Mahdi; Hagh, Sasan Rahbar F; Khamaneh, Aylar Shams; Kabiri, Soudabeh; Keshel, Saeed Heidari; Mansourkiaei, Ana

2010-01-01

Poly-N-isopropylacrylamide was successfully grafted onto a polystyrene cell culture dish and γ-preirradiated in air. In this study, the effect of a γ-pre-irradiation dose of radiation (radiation absorbed dosages of 10, 20, 30, 40 KGy) under appropriate temperature and grafting conditions was investigated. The Fourier transform infrared spectroscopy analysis showed the existence of the graft poly-N-isopropylacrylamide (PNIPAAm) on the substrate. The optimal value of the dose for grafting was 40 KGy at 50°C. The scanning electron microscopy and atomic force microscopy (AFM) images clearly showed that increasing the absorbed dose of radiation would increase the amount of grafting. Surface topography and graft thickness in AFM images of the radiated samples showed that the PNIPAAm at the absorbed dose of radiation was properly grafted. The thickness of these grafts was about 50–100 nm. The drop water contact angles of the best grafted sample at 37°C and 10°C were 55.3 ± 1.2° and 61.2 ± 0.9° respectively, which showed the hydrophilicity and hydrophobicity of the grafted surfaces. Differential scanning calorimetry analysis also revealed the low critical solution temperature of the grafted sample to be 32°C. Thermoresponsive polymers were grafted to dishes covalently which allowed fibroblast cells to attach and proliferate at 37°C; the cells also detached spontaneously without using enzymes when the temperature dropped below 32°C. This characteristic proves that this type of grafted material has potential as a biomaterial for cell sheet engineering. PMID:20957116

Exploring the Dynamics and Structure of Soft Colloids at Oil-water Interfaces

NASA Astrophysics Data System (ADS)

Kwok, Man Hin

The ability of solid colloidal particles to physically stabilize emulsions, also referred to as Pickering emulsions, has been studied for a long time since their activity at the interface was discovered one hundred years ago. Pickering emulsions display various interesting phenomena because of it high desorption energy at the interface compared with conventional surfactant stabilizers. In addition, Pickering emulsions are considered to be 'surfactant free' emulsion and the adverse effects of using surfactants could be eliminated. In the past few years, the use of submicrometer, poly(N-isopropylacrylamide) (PNIPAM)-based mcirogel particles for stabilizing emulsions has captured the interest of many scientists. Being soft, the microgels, which are spherical in solution, become deformed at the oil-water interface. This deformability leads to the special dynamic properties of interfacial layers and packing structures, which in turn alters the interfacial tension and the rheological properties of the interface. In addition, being responsiveness, PNIPAM microgels enable emulsions to be prepared and broken on demand. Despite all of the practical advantages and unique properties that have already been demonstrated, the mechanisms that govern emulsion stabilization and destabilization using microgels are far from completely understood. The study of soft colloids at the interface thus is of great academic interest and the fundamental understanding of them is the key to achieve the application potential of such novel materials. This thesis focuses on the dynamics and structure of soft colloidal particles at the oil-water interfaces. First, in order to prepare tailored colloids for the study, the syntheses of multi-responsive PNIPAM microgels with different size, co-monomers, deformability and morphologies were thoroughly investigated. The combination of semi-batch synthesis and temperature-programmed technique resulted in a novel preparation of micron-sized PNIPAM microgels. Various experimental parameters were tested and modified in order to give microgels with optimized quality. The thermo- and pH- responsiveness of these microgels were characterized by laser diffraction and dynamic light scattering (DLS). Next, a novel labeling technique of the soft PNIPAM microgel particles was developed. This technique was based on the physical adsorption of small fluorescent molecules. Instead of chemically bonded dye molecules, these adsorbed fluorescent dyes could move freely inside the polymer network of the microgel particle. It was also found that the fluorescent dye interacted with different parts of the microgel differently. Therefore, the internal structure and morphology of microgels could be directly visualized by confocal laser scanning microscopy (CLSM) in aqueous environment. The improvement of imaging techniques of microgel particles is essential for studying their behavior at the oil-water interface. It is because conventional scanning electron microscopy (SEM) requires dried sample, which might not reflects the actual states of microgels in aqueous environment. With the improved labeling method under CLSM mentioned above, the conformation of micron-sized PNIPAM microgel particles was captured at the oil-water interface. Particularly, anisotropic deformation of soft pH-responsive microgels was observed at the oil-water interface. Nevertheless, it was found that microgels were not likely to deform significantly unless they were extremely swollen. We also use Langmuir trough to study the dynamics of microgel at an interface with changing area. Forced desorption-spontaneous adsorption cycles of microgel particles at the oil-water interface were successfully demonstrated. More interestingly, it was discovered that the microgel particles would be desorbed before having a significant deformation in Langmuir trough compression. Finally, the emulsion stability of the microgel stabilized Pickering emulsion was characterized by centrifugation. By comparing the stability of different microgels in different conditions, the correlation between the microgel properties and the corresponding Pickering emulsion stability was found. The emulsion stability and the interfacial behaviors of PNIPAM based microgels can now be better controlled and predicted, which gives great advantages for future applications using soft colloids as stabilizers.

Fabrication and Characterization of Thermoresponsive Films Deposited by an RF Plasma Reactor

PubMed Central

Lucero, Adrianne E.; Reed, Jamie A.; Wu, Xiaomei; Canavan, Heather E.

2014-01-01

Summary Poly(N-isopropyl acrylamide) (pNIPAM) undergoes a sharp property change in response to a moderate thermal stimulus at physiological temperatures. In this work, we constructed a radio frequency (RF) plasma reactor for the plasma polymerization of pNIPAM. RF deposition is a method that coats surfaces of any geometry producing surfaces that are sterile and uniform, making this technique useful for forming biocompatible films. The films generated are characterized using X-ray photoelectron spectroscopy (XPS), contact angles, cell culture, and interferometry. We find that a plasma with a decreasing series of power settings (i.e., from 100W to 1W) at a pressure of 140 millitorr yields the most favorable results. PMID:24634643

Novel smart chiral magnetic microspheres for enantioselective adsorption of tryptophan enantiomers

NASA Astrophysics Data System (ADS)

Guo, Lian-Di; Song, Ya-Ya; Yu, Hai-Rong; Pan, Li-Ting; Cheng, Chang-Jing

2017-06-01

Multifunctional microspheres simultaneously possessing chirality, magnetism and thermosensitivity show great potentials in direct enantiomeric separation. Herein we report a novel type of smart chiral magnetic microspheres with core/shell/shell structures (Fe3O4@SiO2@PNCD) and its application in enantioselective adsorption of tryptophan (Trp) enantiomers. The prepared Fe3O4@SiO2@PNCD are composed of a Fe3O4 nanoparticle core, an acidic-resistant SiO2 middle shell and a thermosensitive microgel functional shell (PNCD). The PNCD plays an important role in the enantioselective adsorption of Trp enantiomers. The β-cyclodextrin (β-CD) molecules on the PNCD act as smart receptors or chiral selectors, and can selectively recognize and bind L-Trp enantiomers into their cavities by forming host-guest inclusion complexes. The poly(N-isopropylacrylamide) (PNIPAM) chains on the PNCD serve as microenvironmental adjustors for the association constants of β-CD/L-Trp complexes. The fabricated Fe3O4@SiO2@PNCD demonstrate fascinating temperature-responsive chiral recognition and adsorption selectivity toward Trp enantiomers. Most importantly, the desorption of Trp enantiomers and the regeneration of the Fe3O4@SiO2@PNCD can be easily achieved via simply changing the operation temperature. Moreover, the regenerated Fe3O4@SiO2@PNCD can be readily recovered from the amino acids enantiomeric solution under an external magnetic field for reuse. The present study provides a novel strategy for the direct enantioselective adsorption and separation of various enantiomeric compounds.

Exploring Thermoresponsive Affinity Agents to Enhance Microdialysis Sampling Efficiency of Proteins

NASA Astrophysics Data System (ADS)

Vasicek, Thaddeus

Affinity agents increase microdialysis protein relative recovery, yet they have not seen widespread use within the microdialysis community due to their additional instrumentation requirements and prohibitive cost. This dissertation describes new affinity agents for microdialysis that require no additional instrumentation to use, have nearly 100% particle recovery, are 7 times more cost efficient than alternatives, and have low specificity enabling their use for a wide variety of proteins. Initially gold nanoparticles were chosen as an affinity ligand support due to their high surface area/volume ratio and colloidal stability. Poly (N-isopropylacrylamide) was immobilized to the gold nanoparticles, which served to sterically stabilize the particles and to act as a generic, reversible protein capture agent. A method was developed to reproducibly vary and quantify poly (N-isopropylacrylamide) graft density from 0.09 to 0.40 ligands/nm2 on gold nanoparticles. During characterization of the polymer coated gold nanoparticles, irreversible particle agglomeration was observed at low polymer graft density in ionic solutions, which prevented further development as a protein capture agent. Poly (N-isopropylacrylamide) nanogels, which have low nonspecific adsorption, low interparticle attractive forces owing to the low curvature of the particle, and a low Hamaker constant, were synthesized to overcome the agglomeration problem. A generic protein affinity ligand cibacron blue, was immobilized to the nanogels, which enabled rapid determination of particle recovery. The perfusion of the nanogels through a microdialysis probe was optimized yielding 100% particle recovery using a combination of a syringe and peristaltic pump. The microdialysis collection efficiency of CCL2, a physiologically relevant cytokine, was increased 3-fold with addition of the nanogel to the microdialysis perfusion fluid. The reduction in instrumentation requirements, low cost, and low specificity obtained with the new affinity agents will lead to increased affinity agent use for microdiaylsis protein sampling.

Highly temperature responsive core-shell magnetic particles: synthesis, characterization and colloidal properties.

PubMed

Rahman, Md Mahbubor; Chehimi, Mohamed M; Fessi, Hatem; Elaissari, Abdelhamid

2011-08-15

Temperature responsive magnetic polymer submicron particles were prepared by two step seed emulsion polymerization process. First, magnetic seed polymer particles were obtained by emulsion polymerization of styrene using potassium persulfate (KPS) as an initiator and divinylbenzne (DVB) as a cross-linker in the presence of oil-in-water magnetic emulsion (organic ferrofluid droplets). Thereafter, DVB cross-linked magnetic polymer particles were used as seed in the precipitation polymerization of N-isopropylacrylamide (NIPAM) to induce thermosensitive PNIPAM shell onto the hydrophobic polymer surface of the cross-linked magnetic polymer particles. To impart cationic functional groups in the thermosensitive PNIPAM backbone, the functional monomer aminoethylmethacrylate hydrochloride (AEMH) was used to polymerize with NIPAM while N,N'-methylenebisacrylamide (MBA) and 2, 2'-azobis (2-methylpropionamidine) dihydrochloride (V-50) were used as a cross-linker and as an initiator respectively. The effect of seed to monomer (w/w) ratio along with seed nature on the final particle morphology was investigated. Dynamic light scattering (DLS) results demonstrated particles swelling at below volume phase transition temperature (VPTT) and deswelling above the VPTT. The perfect core (magnetic) shell (polymer) structure of the particles prepared was confirmed by Transmission Electron Microscopy (TEM). The chemical composition of the particles were determined by thermogravimetric analysis (TGA). The effect of temperature, pH, ionic strength on the colloidal properties such as size and zeta potential of the micron sized thermo-sensitive magnetic particles were also studied. In addition, a short mechanistic discussion on the formation of core-shell morphology of magnetic polymer particles has also been discussed. Copyright © 2011 Elsevier Inc. All rights reserved.

Structure-Property Evaluation of Thermally and Chemically Gelling Injectable Hydrogels for Tissue Engineering

PubMed Central

Ekenseair, Adam K.; Boere, Kristel W. M.; Tzouanas, Stephanie N.; Vo, Tiffany N.; Kasper, F. Kurtis; Mikos, Antonios G.

2012-01-01

The impact of synthesis and solution formulation parameters on the swelling and mechanical properties of a novel class of thermally and chemically gelling hydrogels combining poly(N-isopropylacrylamide)-based thermogelling macromers containing pendant epoxy rings with polyamidoamine-based hydrophilic and degradable diamine crosslinking macromers was evaluated. Through variation of network hydrophilicity and capacity for chain rearrangement, the often problematic tendency of thermogelling hydrogels to undergo significant syneresis was addressed. The demonstrated ability to easily tune post-formation dimensional stability at both the synthesis and formulation stages represents a significant novel contribution towards efforts to utilize poly(N-isopropylacrylamide)-based polymers as injectable biomaterials. Furthermore, the cytocompatibility of the hydrogel system under relevant conditions was established, while demonstrating time- and dose-dependent cytotoxicity at high solution osmolality. Such injectable in situ forming degradable hydrogels with tunable water content are promising candidates for many tissue engineering applications, particularly for cell delivery to promote rapid tissue regeneration in non-load-bearing defects. PMID:22881074

The Conformation of Thermoresponsive Polymer Brushes Probed by Optical Reflectivity.

PubMed

Varma, Siddhartha; Bureau, Lionel; Débarre, Delphine

2016-04-05

We describe a microscope-based optical setup that allows us to perform space- and time-resolved measurements of the spectral reflectance of transparent substrates coated with ultrathin films. This technique is applied to investigate the behavior in water of thermosensitive polymer brushes made of poly(N-isopropylacrylamide) grafted on glass. We show that spectral reflectance measurements yield quantitative information about the conformation and axial structure of the brushes as a function of temperature. We study how parameters such as grafting density and chain length affect the hydration state of a brush, and provide one of the few experimental evidences for the occurrence of vertical phase separation in the vicinity of the lower critical solution temperature of the polymer. The origin of the hysteretic behavior of poly(N-isopropylacrylamide) brushes upon cycling the temperature is also clarified. We thus demonstrate that our optical technique allows for in-depth characterization of stimuli-responsive polymer layers, which is crucial for the rational design of smart polymer coatings in actuation, gating, or sensing applications.

Designing a Poly (N-isopropylacrylamide) Nanocapsule for Magnetic Field-assisted Drug Delivery

NASA Astrophysics Data System (ADS)

Denmark, Daniel; Mukherjee, Pritish; Witanachchi, Sarath

2014-03-01

The method of synthesis and the characteristics of polymer based nanocapsules as biomedical drug delivery systems are presented. Magnetic iron oxide nanoparticles have been incorporated into these capsules for effective guidance with external magnetic fields to transport therapeutic compounds to various parts of the human body. Once they have reached their destination they can be stimulated to release the drug to the target tissue through externally applied fields. The polymeric material that constitutes the capsules is specifically designed to melt away with the external stimuli to deliver the therapeutic bio agents near the target tissue. In this work we use nebulization to create aqueous poly (N-isopropylacrylamide) nanoparticles that decompose after being heated beyond their transition temperature. Transmission Electron Microscopic imaging (TEM) and dynamic light scattering (DLS) experiments have been conducted to study the decomposition of the capsules under external stimuli. Distribution of the magnetic nanoparticles within the capsules and their role in delivering the bio agents have been investigated by the Magnetic Force Microscopy (MFM).

Assessment of the biocompatibility, stability, and suitability of novel thermoresponsive films for the rapid generation of cellular constructs

NASA Astrophysics Data System (ADS)

Reed, Jamie A.

2011-12-01

Stimuli responsive polymers (SRP) are of great interest in the bioengineering community due to their use in applications such as drug delivery and tissue engineering. One example of an SRP is poly(N-isopropyl acrylamide) or pNIPAM. This SRP has the capability of changing its conformation with a slight temperature change: adherent mammalian cells spontaneously release as a confluent cell sheet, which can be harvested for cell sheet engineering purposes. Since its initial use in 1968, many researchers have used pNIPAM to obtain a cell sheet composed of their cell type of interest. The differing protocols used for these diverse cell types, such as the conditions used for cell detachment, and the varying methods used for derivatizing substrates with pNIPAM have all led to conflicting reports on the utility of pNIPAM for cell sheet engineering purposes, as well as the relative cytotoxicity of the polymer. In this work, some of the key inconsistencies in the literature and previously unaddressed challenges when utilizing pNIPAM films are overcome for the purpose of rapid generation of cellular constructs, specifically spheroids. Pertinent characteristics of low temperature detachment are investigated for their effect on the kinetics of cell detachment. In addition, a novel, inexpensive method for obtaining pNIPAM films for mammalian cell detachment, combining pNIPAM with a sol-gel, was optimized and compared to plasma polymerization deposition. Furthermore, proper storage conditions (e.g. temperature and relative humidity) for these films were investigated to increase stability of the films for using tissue culture conditions. To increase the speed of generation of cell sheets, electrospun mats and hydrogels with a high surface area-to-volume ratio were developed. The result is a platform appropriate for the rapid formation of cellular constructs, such as engineered tissues and spheroids for cancer cell research.

Design of Polymer Networks Involving a Photoinduced Electronic Transmission Circuit toward Artificial Photosynthesis.

PubMed

Okeyoshi, Kosuke; Kawamura, Ryuzo; Yoshida, Ryo; Osada, Yoshihito

2016-01-19

Many strategies have been explored to achieve artificial photosynthesis utilizing mediums such as liposomes and supramolecules. Because the photochemical reaction is composed of multiple functional molecules, the surrounding microenvironment is expected to be rationally integrated as observed during photosynthesis in chloroplasts. In this study, photoinduced electronic transmission surrounding the microenvironment of Ru(bpy)3(2+) in a polymer network was investigated using poly(N-isopropylacrylamide-co-Ru(bpy)3), poly(acrylamide-co-Ru(bpy)3), and Ru(bpy)3-conjugated microtubules. Photoinduced energy conversion was evaluated by investigating the effects of (i) Ru(bpy)3(2+) immobilization, (ii) polymer type, (iii) thermal energy, and (iv) cross-linking. The microenvironment surrounding copolymerized Ru(bpy)3(2+) in poly(N-isopropylacrylamide) suppressed quenching and had a higher radiative process energy than others. This finding is related to the nonradiative process, i.e., photoinduced H2 generation with significantly higher overall quantum efficiency (13%) than for the bulk solution. We envision that useful molecules will be generated by photoinduced electronic transmission in polymer networks, resulting in the development of a wide range of biomimetic functions with applications for a sustainable society.

Data of continuous harvest of stem cells via partial detachment from thermoresponsive nanobrush surfaces

PubMed Central

Yeh, Chin-Chen; Muduli, Saradaprasan; Peng, I-Chia; Lu, Yi-Tung; Ling, Qing-Dong; Alarfaj, Abdullah A.; Munusamy, Murugan A.; Kumar, S. Suresh; Murugan, Kadarkarai; Chen, Da-Chung; Lee, Hsin-chung; Chang, Yung; Higuchi, Akon

2016-01-01

This data article contains two figures and one table supporting the research article entitled: “Continuous harvest of stem cells via partial detachment from thermoresponsive nanobrush surface” [1]. The table shows coating conditions of three copolymers, poly(styrene-co-acrylic acid) grafted with oligovitronectin, poly(styrene-co-N-isopropylacrylamide) and poly(styrene-co-polyethylene glycol methacrylate) to prepare thermoresponsive surface. XPS spectra show the nitrogen peak of the polystyrene surface coated with poly(styrene-co-acrylic acid) grafted with oligovitronectin. The surface coating density analyzed from sorption of poly(styrene-co-acrylic acid) grafted with oligovitronectin by UV–vis spectroscopy is also presented. PMID:26909373

Core Scientific Effort for Biosurface Studies (TASK I).

DTIC Science & Technology

1992-06-30

using acrylamide (I) and both monosubstituted and disubstituted (on nitrogen) acrylamide derivatives (II and LI). CH2 = CH-CO-NH2 CH2 = CH-CO-NHR...of seven different monomers onto poly(ethylene terephthalate), PET. The grafted monomers are: acrylamide , N- isopropylacrylamide, N,N...comprehensive study (as an M.S. thesis) of the grafting of acrylamide on to surface- treated polyolefins is nearing completion. Acrylamide can be

The effect of the processing and formulation parameters on the size of nanoparticles based on block copolymers of poly(ethylene glycol) and poly(N-isopropylacrylamide) with and without hydrolytically sensitive groups.

PubMed

Neradovic, D; Soga, O; Van Nostrum, C F; Hennink, W E

2004-05-01

Block copolymers of poly(ethylene glycol) (PEG) as a hydrophilic block and N-isopropylacrylamide (PNIPAAm) or poly (NIPAAm-co-N-(2-hydroxypropyl) methacrylamide-dilactate) (poly(NIPAAm-co-HPMAm-dilactate)) as a thermosensitive block, are able to self-assemble in water into nanoparticles above the cloud point (CP) of the thermosensitive block. The influence of processing and the formulation parameters on the size of the nanoparticles was studied using dynamic light scattering. PNIPAAm-b-PEG 2000 polymers were not suitable for the formation of small and stable particles. Block copolymers with PEG 5000 and 10000 formed relatively small and stable particles in aqueous solutions at temperatures above the CP of the thermosensitive block. Their size decreased with increasing molecular weight of the thermosensitive block, decreasing polymer concentration and using water instead of phosphate buffered saline as solvent. Extrusion and ultrasonication were inefficient methods to size down the polymeric nanoparticles. The heating rate of the polymer solutions was a dominant factor for the size of the nanoparticles. When an aqueous polymer solution was slowly heated through the CP, rather large particles (> or = 200 nm) were formed. Regardless the polymer composition, small nanoparticles (50-70 nm) with a narrow size distribution were formed, when a small volume of an aqueous polymer solution below the CP was added to a large volume of heated water. In this way the thermosensitive block copolymers rapidly pass their CP ('heat shock' procedure), resulting in small and stable nanoparticles.

Protein valves prepared by click reaction grafting of poly(N-isopropylacrylamide) to electrospun poly(vinyl chloride) fibrous membranes

NASA Astrophysics Data System (ADS)

Guo, Jian-Wei; Lin, Zhen-Yu; Chang, Chi-Jung; Lu, Chien-Hsing; Chen, Jem-Kun

2018-05-01

In this study, poly(vinyl chloride) (PVC) was electrospun into fibrous membranes and then reacted with NaN3 to generate azido-terminated PVC fibrous membranes. A propargyl-terminated poly(N-isopropylacrylamide) (PNIPAAm) was also synthesized and then grafted, through click reactions, onto the azido-terminated PVC fiber surface. Protrusion-, scale-, and joint-like structures of the PNIPAAm grafts on the PVC fibers were formed upon increasing the molecular weight of the PNIPAAm grafts. The PNIPAAm-grafted PVC fibrous mats exhibited completely wetted surfaces at 25 °C because of their high roughness. The static water contact angle of the PNIPAAm-grafted PVC fibrous mats reached 140° when the temperature was increased to 45 °C. This thermoresponsive behavior was significantly greater than that of the PNIPAAm grafted on a flat surface. Temperature-responsive membranes were constructed having a pore size of 1.38 μm and applied as protein valves to block and release an antibody (fluorescein-conjugated AffiniPure goat anti-rabbit IgG). At 25 °C, the collection efficiency remained at 94% for antibody concentrations up to 60 ng/L. As the temperature increased to 45 °C, the collection efficiency decreased abruptly, to 4%, when the antibody concentration was greater than 20 ng/L. Accordingly, this system of PNIPAAm-grafted PVC fibers functioned as a protein valve allowing the capture and concentration of proteins.

Passive targeting of thermosensitive diblock copolymer micelles to the lungs: synthesis and characterization of poly(N-isopropylacrylamide)-block-poly(ε-caprolactone).

PubMed

Lee, Ren-Shen; Lin, Chih-Hung; Aljuffali, Ibrahim A; Hu, Kai-Yin; Fang, Jia-You

2015-06-18

Amphiphilic poly(N-isopropylacrylamide)-block-poly(ε-caprolactone) (PNiPAAm-b-PCL) copolymers were synthesized by ring-opening polymerization to form thermosensitive micelles as nanocarriers for bioimaging and carboplatin delivery. The critical micelle concentration increased from 1.8 to 3.5 mg/l following the decrease of the PNiPAAm chain length. The copolymers revealed a lower critical solution temperature (LCST) between 33 and 40°C. The copolymers self-assembled to form spherical particles of 146-199 nm in diameter. Carboplatin in micelles exhibited a slower release at 37°C relative to that at 25°C due to the gel layer formation on the micellar shell above the LCST. The micelles containing dye or carboplatin were intravenously injected into the rats for in vivo bioimaging and drug biodistribution. The bioimaging profiles showed a significant accumulation of micelles in the lungs. The micelles could minimize the reticuloendothelial system (RES) recognition of the dye. In vivo biodistribution demonstrated an improved pulmonary accumulation of carboplatin from 2.5 to 3.4 μg/mg by the micelles as compared to the control solution. Carboplatin accumulation in the heart and kidneys was reduced after encapsulation by the micelles. This study supports the potential of PNiPAAm-b-PCL micelles to passively target the lungs and attenuate RES uptake and possible side effects.

Development of thermosensitive poly(n-isopropylacrylamide-co-((2-dimethylamino) ethyl methacrylate))-based nanoparticles for controlled drug release

NASA Astrophysics Data System (ADS)

Peng, Cheng-Liang; Tsai, Han-Min; Yang, Shu-Jyuan; Luo, Tsai-Yueh; Lin, Chia-Fu; Lin, Wuu-Jyh; Shieh, Ming-Jium

2011-07-01

Thermosensitive nanoparticles based on poly(N-isopropylacrylamide-co-((2-dimethylamino)ethylmethacrylate)) (poly(NIPA-co-DMAEMA)) copolymers were successfully fabricated by free radical polymerization. The lower critical solution temperature (LCST) of the synthesized nanoparticles was 41 °C and a temperature above which would cause the nanoparticles to undergo a volume phase transition from 140 to 100 nm, which could result in the expulsion of encapsulated drugs. Therefore, we used the poly(NIPA-co-DMAEMA) nanoparticles as a carrier for the controlled release of a hydrophobic anticancer agent, 7-ethyl-10-hydroxy-camptothecin (SN-38). The encapsulation efficiency and loading content of SN-38-loaded nanoparticles at an SN-38/poly(NIPA-co-DMAEMA) ratio of 1/10 (D/P = 1/10) were about 80% and 6.293%, respectively. Moreover, the release profile of SN-38-loaded nanoparticles revealed that the release rate at 42 °C (above LCST) was higher than that at 37 °C (below LCST), which demonstrated that the release of SN-38 could be controlled by increasing the temperature. The cytotoxicity of the SN-38-loaded poly(NIPA-co-DMAEMA) nanoparticles was investigated in human colon cancer cells (HT-29) to compare with the treatment of an anticancer drug, Irinotecan® (CPT-11). The antitumor efficacy evaluated in a C26 murine colon tumor model showed that the SN-38-loaded nanoparticles in combination with hyperthermia therapy efficiently suppressed tumor growth. The results indicate that these thermo-responsive nanoparticles are potential carriers for controlled drug delivery.

Synthesis of biodegradable plastic from tapioca with N-Isopropylacrylamid and chitosan using glycerol as plasticizer

NASA Astrophysics Data System (ADS)

Syaubari; Safwani, S.; Riza, M.

2018-04-01

One of natural polymers that can be used as raw material in the manufacture of biodegradable plastic is tapioca and chitosan. The addition of other compounds such as glycerol as plasticizer is to improve the characteristics of the plastic that already produced. N- Isopropylacrylamid (NIPAm) is an organic compound that can be synthesized into a polymer or polymer grafting which also biodegradable too. This research aims tostudy the synthesis of biodegradable plastics from tapioca with the addition of chitosan, NIPAm, poly(NIPAm) and analyze the characteristics of biodegradable plastics that already produced. This research was done in three stages, there are (1) polymerization NIPAm, (2) the grafting of chitosan-poly NIPAm and (3) the synthesis of biodegradable plastics from starch mixture with variation of addition chitosan, NIPAm, poly(NIPAm), chitosan-graft-poly(NIPAm) and also variations of glycerol as plasticizer. The results of this research is a thin sheet of plastic which is will get analyzed for the characteristics of functional groups, mechanical, morphological and its biodegradability. FTIR spectra showed the grafting process with the new group formation of CO single-bond at 850 cm-1. Plastic with the addition of NIPAm and 1 ml glycerol has the highest tensile strength value about 31.1 MPa. Plastic with poly(NIPAm) and 4 ml glycerol produces the highest elongation value about 153.72%. Plastic with Chitosan-graft-poly(NIPAm) with 1 ml glycerol has the longest biodegradation because of the small mass-loss for six weeks which is about 6.6%.

Reversible Polymer Hydrogels

DTIC Science & Technology

2008-12-01

glucosamine hydrochloride was dissolved in 100 mL of de- ionized water and placed in an ice bath at >5oC and purged with N2 gas for 20 minutes; 3.25...Temperature sensitive hydrogels based on N-isopropyl acrylamide (NIPA) and acryloyl glucosamine (AG) were synthesized using ammonium persulfate (APS) as...hydrogels by copolymerization of poly (N-isopropylacrylamide) (NIPA), and acryloyl glucosamine (AG) a derivative of chi- tosan, a biopolymer from

Hg2+-reactive double hydrophilic block copolymer assemblies as novel multifunctional fluorescent probes with improved performance.

PubMed

Hu, Jinming; Li, Changhua; Liu, Shiyong

2010-01-19

We report on novel type of responsive double hydrophilic block copolymer (DHBC)-based multifunctional chemosensors to Hg(2+) ions, pH, and temperatures and investigate the effects of thermo-induced micellization on the detection sensitivity. Well-defined DHBCs bearing rhodamine B-based Hg(2+)-reactive moieties (RhBHA) in the thermo-responsive block, poly(ethylene oxide)-b-poly(N-isopropylacrylamide-co-RhBHA) (PEO-b-P(NIPAM-co-RhBHA)), were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Nonfluorescent RhBHA moieties are subjected to selective ring-opening reaction upon addition of Hg(2+) ions or lowering solution pH, producing highly fluorescent acyclic species. Thus, at room temperature PEO-b-P(NIPAM-co-RhBHA) DHBCs can serve as water-soluble multifunctional and efficient fluorescent chemosensors to Hg(2+) ions and pH. Upon heating above the lower critical solution temperature (approximately 36 degrees C) of the PNIPAM block, they self-assemble into micelles possessing P(NIPAM-co-RhBHA) cores and well-solvated PEO coronas, which were fully characterized by dynamic and static laser light scattering. It was found that the detection sensitivity to Hg(2+) ions and pH could be dramatically improved at elevated temperatures due to fluorescence enhancement of RhBHA residues in the acyclic form, which were embedded within hydrophobic cores of thermo-induced micellar aggregates. This work represents a proof-of-concept example of responsive DHBC-based multifunctional fluorescent chemosensors for the highly efficient detection of Hg(2+) ions, pH, and temperatures with tunable detection sensitivity. Compared to reaction-based small molecule Hg(2+) probes in previous literature reports, the integration of stimuli-responsive block copolymers with well-developed small molecule-based selective sensing moieties in the current study are expected to exhibit preferred advantages including enhanced detection sensitivity, water dispersibility, biocompatibility, facile incorporation into devices, and the ability of further functionalization for targeted imaging and detection.

UV-crosslinkable and thermo-responsive chitosan hybrid hydrogel for NIR-triggered localized on-demand drug delivery.

PubMed

Wang, Lei; Li, Baoqiang; Xu, Feng; Xu, Zheheng; Wei, Daqing; Feng, Yujie; Wang, Yaming; Jia, Dechang; Zhou, Yu

2017-10-15

Innovative drug delivery technologies based on smart hydrogels for localized on-demand drug delivery had aroused great interest. To acquire smart UV-crosslinkable chitosan hydrogel for NIR-triggered localized on-demanded drug release, a novel UV-crosslinkable and thermo-responsive chitosan was first designed and synthesized by grafting with poly N-isopropylacrylamide, acetylation of methacryloyl groups and embedding with photothermal carbon. The UV-crosslinkable unit (methacryloyl groups) endowed chitosan with gelation via UV irradiation. The thermo-responsive unit (poly N-isopropylacrylamide) endowed chitosan hydrogel with temperature-triggered volume shrinkage and reversible swelling/de-swelling behavior. The chitosan hybrid hydrogel embedded with photothermal carbon exhibited distinct NIR-triggered volume shrinkage (∼42% shrinkage) in response to temperature elevation as induced by NIR laser irradiation. As a demonstration, doxorubicin release rate was accelerated and approximately 40 times higher than that from non-irradiated hydrogels. The UV-crosslinkable and thermal-responsive hybrid hydrogel served as in situ forming hydrogel-based drug depot is developed for NIR-triggered localized on-demand release. Copyright © 2017 Elsevier Ltd. All rights reserved.

Catalysis by Metallic Nanoparticles in Solution: Thermosensitive Microgels as Nanoreactors

NASA Astrophysics Data System (ADS)

Roa, Rafael; Angioletti-Uberti, Stefano; Lu, Yan; Dzubiella, Joachim; Piazza, Francesco; Ballauff, Matthias

2018-05-01

Metallic nanoparticles have been used as catalysts for various reactions, and the huge literature on the subject is hard to overlook. In many applications, the nanoparticles must be affixed to a colloidal carrier for easy handling during catalysis. These "passive carriers" (e.g. dendrimers) serve for a controlled synthesis of the nanoparticles and prevent coagulation during catalysis. Recently, hybrids from nanoparticles and polymers have been developed that allow us to change the catalytic activity of the nanoparticles by external triggers. In particular, single nanoparticles embedded in a thermosensitive network made from poly(N-isopropylacrylamide) (PNIPAM) have become the most-studied examples of such hybrids: immersed in cold water, the PNIPAM network is hydrophilic and fully swollen. In this state, hydrophilic substrates can diffuse easily through the network, and react at the surface of the nanoparticles. Above the volume transition located at 32°C, the network becomes hydrophobic and shrinks. Now hydrophobic substrates will preferably diffuse through the network and react with other substrates in the reaction catalyzed by the enclosed nanoparticle. Such "active carriers", may thus be viewed as true nanoreactors that open new ways for the use of nanoparticles in catalysis. In this review, we give a survey on recent work done on these hybrids and their application in catalysis. The aim of this review is threefold: we first review hybrid systems composed of nanoparticles and thermosensitive networks and compare these "active carriers" to other colloidal and polymeric carriers (e.g. dendrimers). In a second step we discuss the model reactions used to obtain precise kinetic data on the catalytic activity of nanoparticles in various carriers and environments. These kinetic data allow us to present a fully quantitative comparison of different nanoreactors. In a final section we shall present the salient points of recent efforts in the theoretical modeling of these nanoreactors. By accounting for the presence of a free-energy landscape for the reactants' diffusive approach towards the catalytic nanoparticle, arising from solvent-reactant and polymeric shell-reactant interactions, these models are capable of explaining the emergence of all the important features observed so far in studies of nanoreactors. The present survey also suggests that such models may be used for the design of future carrier systems adapted to a given reaction and solvent.

Temperature sensitive surfaces and methods of making same

DOEpatents

Liang, Liang [Richland, WA; Rieke, Peter C [Pasco, WA; Alford, Kentin L [Pasco, WA

2002-09-10

Poly-n-isopropylacrylamide surface coatings demonstrate the useful property of being able to switch charateristics depending upon temperature. More specifically, these coatings switch from being hydrophilic at low temperature to hydrophobic at high temperature. Research has been conducted for many years to better characterize and control the properties of temperature sensitive coatings. The present invention provides novel temperature sensitive coatings on articles and novel methods of making temperature sensitive coatings that are disposed on the surfaces of various articles. These novel coatings contain the reaction products of n-isopropylacrylamide and are characterized by their properties such as advancing contact angles. Numerous other characteristics such as coating thickness, surface roughness, and hydrophilic-to-hydrophobic transition temperatures are also described. The present invention includes articles having temperature-sensitve coatings with improved properties as well as improved methods for forming temperature sensitive coatings.

Assessing the Efficacy of Poly(N-isopropylacrylamide) for Drug Delivery Applications Using Molecular Dynamics Simulations.

PubMed

Moghadam, Soroush; Larson, Ronald G

2017-02-06

All-atom molecular dynamic simulations (AA-MD) are performed for aqueous solutions of hydrophobic drug molecules (phenytoin) with model polymer excipients, namely, (1) N-isopropylacrylamide, (pNIPAAm), (2) pNIPAAm-co-acrylamide (Am), and (3) pNIPAAm-co-dimethylacrylamide (DMA). After validating the force field parameters using the well-known lower critical solution behavior of pNIPAAm, we simulate the polymer-drug complex in water and its behavior at temperatures below (295 K) and above the LCST (310 K). Using radial distribution functions, we find that there is an optimum comonomer molar fraction of around 20-30% DMA at which interaction with phenytoin drug molecules is strongest, consistent with recent experimental findings. The results provide evidence that molecular simulations are able to provide guidance in the optimization of novel polymer excipients for drug release.

Multiple-stimuli responsive bioelectrocatalysis based on reduced graphene oxide/poly(N-isopropylacrylamide) composite films and its application in the fabrication of logic gates.

PubMed

Wang, Lei; Lian, Wenjing; Yao, Huiqin; Liu, Hongyun

2015-03-11

In the present work, reduced graphene oxide (rGO)/poly(N-isopropylacrylamide) (PNIPAA) composite films were electrodeposited onto the surface of Au electrodes in a fast and one-step manner from an aqueous mixture of a graphene oxide (GO) dispersion and N-isopropylacrylamide (NIPAA) monomer solutions. Reflection-absorption infrared (IR) and Raman spectroscopies were employed to characterize the successful construction of the rGO/PNIPAA composite films. The rGO/PNIPAA composite films exhibited reversible potential-, pH-, temperature-, and sulfate-sensitive cyclic voltammetric (CV) on-off behavior to the electroactive probe ferrocenedicarboxylic acid (Fc(COOH)2). For instance, after the composite films were treated at -0.7 V for 7 min, the CV responses of Fc(COOH)2 at the rGO/PNIPAA electrodes were quite large at pH 8.0, exhibiting the on state. However, after the films were treated at 0 V for 30 min, the CV peak currents became much smaller, demonstrating the off state. The mechanism of the multiple-stimuli switchable behaviors for the system was investigated not only by electrochemical methods but also by scanning electron microscopy and X-ray photoelectron spectroscopy. The potential-responsive behavior for this system was mainly attributed to the transformation between rGO and GO in the films at different potentials. The film system was further used to realize multiple-stimuli responsive bioelectrocatalysis of glucose catalyzed by the enzyme of glucose oxidase and mediated by the electroactive probe of Fc(COOH)2 in solution. On the basis of this, a four-input enabled OR (EnOR) logic gate network was established.

Influence of Temperature on the Colloidal Stability of Polymer-Coated Gold Nanoparticles in Cell Culture Media.

PubMed

Zyuzin, Mikhail V; Honold, Tobias; Carregal-Romero, Susana; Kantner, Karsten; Karg, Matthias; Parak, Wolfgang J

2016-04-06

The temperature-dependence of the hydrodynamic diameter and colloidal stability of gold-polymer core-shell particles with temperature-sensitive (poly(N-isopropylacrylamide)) and temperature-insensitive shells (polyallylaminine hydrochloride/polystyrensulfonate, poly(isobutylene-alt-maleic anhydride)-graft-dodecyl) are investigated in various aqueous media. The data demonstrate that for all nanoparticle agglomeration, i.e., increase in effective nanoparticle size, the presence of salts or proteins in the dispersion media has to be taken into account. Poly(N-isopropylacrylamide) coated nanoparticles show a reversible temperature-dependent increase in size above the volume phase transition of the polymer shell when they are dispersed in phosphate buffered saline or in media containing protein. In contrast, the nanoparticles coated with temperature-insensitive polymers show a time-dependent increase in size in phosphate buffered saline or in medium containing protein. This is due to time-dependent agglomeration, which is particularly strong in phosphate buffered saline, and induces a time-dependent, irreversible increase in the hydrodynamic diameter of the nanoparticles. This demonstrates that one has to distinguish between temperature- and time-induced agglomerations. Since the size of nanoparticles regulates their uptake by cells, temperature-dependent uptake of thermosensitive and non-thermosensitive nanoparticles by cells lines is compared. No temperature-specific difference between both types of nanoparticles could be observed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Combining cell sheet technology and electrospun scaffolding for engineered tubular, aligned, and contractile blood vessels.

PubMed

Rayatpisheh, Shahrzad; Heath, Daniel E; Shakouri, Amir; Rujitanaroj, Pim-On; Chew, Sing Yian; Chan-Park, Mary B

2014-03-01

Herein we combine cell sheet technology and electrospun scaffolding to rapidly generate circumferentially aligned tubular constructs of human aortic smooth muscles cells with contractile gene expression for use as tissue engineered blood vessel media. Smooth muscle cells cultured on micropatterned and N-isopropylacrylamide-grafted (pNIPAm) polydimethylsiloxane (PDMS), a small portion of which was covered by aligned electrospun scaffolding, resulted in a single sheet of unidirectionally aligned cells. Upon cooling to room temperature, the scaffold, its adherent cells, and the remaining cell sheet detached and were collected on a mandrel to generating tubular constructs with circumferentially aligned smooth muscle cells which possess contractile gene expression and a single layer of electrospun scaffold as an analogue to a small diameter blood vessel's internal elastic lamina (IEL). This method improves cell sheet handling, results in rapid circumferential alignment of smooth muscle cells which immediately express contractile genes, and introduction of an analogue to small diameter blood vessel IEL. Copyright © 2013 Elsevier Ltd. All rights reserved.

Synthesis and characterization of smart N-isopropylacrylamide-based magnetic nanocomposites containing doxorubicin anti-cancer drug.

PubMed

Motaali, Soheila; Pashaeiasl, Maryam; Akbarzadeh, Abolfazl; Davaran, Soodabeh

2017-05-01

In the present study, magnetic and thermo/pH-sensitive (multiresponsive) nanocomposites based on N-isopropylacrylamide (NIPAAM) were synthesized and characterized. Nanocomposites were synthesized by free radical emulsion polymerization of NIPAAM as thermosensitive monomer and N,N-dimethyl-aminoethyl methacrylate (DMAEMA) as pH-sensitive monomer in the presence of methylene-bis-acrylamide as cross-linking agent. Doxorubicin, an anti-cancer drug, was loaded into these nanocomposites via equilibrium swelling method. Thermo/pH-sensitive cross-linked poly (NIPAAM-DMAEMA)-Fe 3 O 4 nanocomposites were characterized by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and vibrating sample magnetometer (VSM). The volume of the loaded drug and drug release amount was determined by UV measurements. The results showed that this thermo/pH-sensitive magnetic nanocomposite has a high drug-loading efficiency. Doxorubicin was released at 40 °C and pH 5.8 more than the 37 °C and pH 7.4.

Inflammation-sensitive in situ smart scaffolding for regenerative medicine.

PubMed

Patra, Hirak K; Sharma, Yashpal; Islam, Mohammad Mirazul; Jafari, Mohammad Javad; Murugan, N Arul; Kobayashi, Hisatoshi; Turner, Anthony P F; Tiwari, Ashutosh

2016-10-06

To cope with the rapid evolution of the tissue engineering field, it is now essential to incorporate the use of on-site responsive scaffolds. Therefore, it is of utmost importance to find new 'Intelligent' biomaterials that can respond to the physicochemical changes in the microenvironment. In this present report, we have developed biocompatible stimuli responsive polyaniline-multiwalled carbon nanotube/poly(N-isopropylacrylamide), (PANI-MWCNT/PNIPAm) composite nanofiber networks and demonstrated the physiological temperature coordinated cell grafting phenomenon on its surface. The composite nanofibers were prepared by a two-step process initiated with an assisted in situ polymerization followed by electrospinning. To obtain a smooth surface in individual nanofibers with the thinnest diameter, the component ratios and electrospinning conditions were optimized. The temperature-gated rearrangements of the molecular structure are characterized by FTIR spectroscopy with simultaneous macromolecular architecture changes reflected on the surface morphology, average diameter and pore size as determined by scanning electron microscopy. The stimuli responsiveness of the nanofibers has first been optimized with computational modeling of temperature sensitive components (coil-like and globular conformations) to tune the mechanism for temperature dependent interaction during in situ scaffolding with the cell membrane. The nanofiber networks show excellent biocompatibility, tested with fibroblasts and also show excellent sensitivity to inflammation to combat loco-regional acidosis that delay the wound healing process by an in vitro model that has been developed for testing the proposed responsiveness of the composite nanofiber networks. Cellular adhesion and detachment are regulated through physiological temperature and show normal proliferation of the grafted cells on the composite nanofibers. Thus, we report for the first time, the development of physiological temperature gated inflammation-sensitive smart biomaterials for advanced tissue regeneration and regenerative medicine.

Thermo-and pH-sensitive hydrogel membranes composed of poly(N-isopropylacrylamide)-hyaluronan for biomedical applications: Influence of hyaluronan incorporation on the membrane properties.

PubMed

Kamoun, Elbadawy A; Fahmy, Alaa; Taha, Tarek H; El-Fakharany, Esmail M; Makram, Mohamed; Soliman, Hesham M A; Shehata, Hassan

2018-01-01

Interpenetrating hydrogel membranes consisting of pH-sensitive hyaluronan (HA) and thermo-sensitive poly(N-isopropylacrylamide) (PNIPAAM) were synthesized using redox polymerization, followed by N,N-methylenebisacrylamide (BIS) and epichlorohydrin (EPI) were added as chemical crosslinkers. The interaction between membrane compositions has been characterized by FTIR spectroscopy and discussed intensively. The result indicates that HA incorporation in membranes increase the gel fraction, swelling uptake, and the flexibility/elasticity of crosslinked membranes, however it reduced oppositely the mechanical elongation of membranes. PNIPAAm-HA hydrogels responded to both temperature and pH changes and the stimuli-responsiveness was reversible. However, in vitro bioevaluation results revealed that the released ampicillin during the burst release time was sharply influenced and increased with increasing HA contents in membranes; afterwards it became sustainable. Whereas, high HA contents in hydrogels unexpectedly impacted negatively on the cells viability, owing to the viscosity of cell culture media changed. A big resistance was observed against microbial growth of Staphylococcus aureus, Salmonella typhi, and Candida albicans in case of pure PNIPAAm hydrogel membranes without HA or ampicillin. However, HA incorporation or the loaded ampicillin in membranes showed unexpected easily microbial growth. The fast release performance with dual pH-thermo-sensitive hydrogels were suggested as promising materials for quick drug carrier in the biomedical field. Copyright © 2017 Elsevier B.V. All rights reserved.

Biological preconcentrator

DOEpatents

Manginell, Ronald P [Albuquerque, NM; Bunker, Bruce C [Albuquerque, NM; Huber, Dale L [Albuquerque, NM

2008-09-09

A biological preconcentrator comprises a stimulus-responsive active film on a stimulus-producing microfabricated platform. The active film can comprise a thermally switchable polymer film that can be used to selectively absorb and desorb proteins from a protein mixture. The biological microfabricated platform can comprise a thin membrane suspended on a substrate with an integral resistive heater and/or thermoelectric cooler for thermal switching of the active polymer film disposed on the membrane. The active polymer film can comprise hydrogel-like polymers, such as poly(ethylene oxide) or poly(n-isopropylacrylamide), that are tethered to the membrane. The biological preconcentrator can be fabricated with semiconductor materials and technologies.

Intelligent anticancer drug delivery performances of two poly(N-isopropylacrylamide)-based magnetite nanohydrogels.

PubMed

Poorgholy, Nahid; Massoumi, Bakhshali; Ghorbani, Marjan; Jaymand, Mehdi; Hamishehkar, Hamed

2018-08-01

This article evaluates the anticancer drug delivery performances of two nanohydrogels composed of poly(N-isopropylacrylamide-co-itaconic anhydride) [P(NIPAAm-co-IA)], poly(ethylene glycol) (PEG), and Fe 3 O 4 nanoparticles. For this purpose, the magnetite nanohydrogels (MNHGs) were loaded with doxorubicin hydrochloride (DOX) as a universal anticancer drug. The morphologies and magnetic properties of the DOX-loaded MNHGs were investigated using transmission electron microscopy (TEM) and vibrating-sample magnetometer (VSM), respectively. The sizes and zeta potentials (ξ) of the MNHGs and their corresponding DOX-loaded nanosystems were also investigated. The DOX-loaded MNHGs showed the highest drug release values at condition of 41 °C and pH 5.3. The drug-loaded MNHGs at physiological condition (pH 7.4 and 37 °C) exhibited negligible drug release values. In vitro cytotoxic effects of the DOX-loaded MNHGs were extensively evaluated through the assessing survival rate of HeLa cells using the MTT assay, and there in vitro cellular uptake into the mentioned cell line were examined using fluorescent microscopy and fluorescence-activated cell sorting (FACS) flow cytometry analyses. As the results, the DOX-loaded MNHG1 exhibited higher anticancer drug delivery performance in the terms of cytotoxic effect and in vitro cellular uptake. Thus, the developed MNHG1 can be considered as a promising de novo drug delivery system, in part due to its pH and thermal responsive drug release behavior as well as proper magnetite character toward targeted drug delivery.

Effects of Complementary DNA and Salt on the Thermoresponsiveness of Poly(N-isopropylacrylamide)-b-DNA.

PubMed

Fujita, Masahiro; Hiramine, Hayato; Pan, Pengju; Hikima, Takaaki; Maeda, Mizuo

2016-02-02

The thermoresponsive structural transition of poly(N-isopropylacrylamide) (PNIPAAm)-b-DNA copolymers was explored. Molecular assembly of the block copolymers was facilitated by adding salt, and this assembly was not nucleated by the association between DNA strands but by the coil-globule transition of PNIPAAm blocks. Below the lower critical solution temperature (LCST) of PNIPAAm, the copolymer solution remained transparent even at high salt concentrations, regardless of whether DNA was hybridized with its complementary partner to form a double-strand (or single-strand) structure. At the LCST, the hybridized copolymer assembled in spherical nanoparticles, surrounded by double-stranded DNA; subsequently, the non-cross-linking aggregation occurred, while the nanoparticles were dispersed if the salt concentration was low or DNA blocks were unhybridized. When the DNA duplex was denatured to a single-stranded state by heating, the aggregated nanoparticles redispersed owing to the recovery of the steric repulsion of the DNA strands. The changes in the steric and electrostatic effects by hybridization and the addition of salt did not result in any specific attraction between DNA strands but merely decreased the repulsive interactions. The van der Waals attraction between the nanoparticles overcame such repulsive interactions so that the non-cross-linking aggregation of the micellar particles was mediated.

Magnetic Poly(N-isopropylacrylamide) Nanocomposites: Effect of Preparation Method on Antibacterial Properties

NASA Astrophysics Data System (ADS)

Nguyen, Nhung H. A.; Darwish, Mohamed S. A.; Stibor, Ivan; Kejzlar, Pavel; Ševců, Alena

2017-10-01

The most challenging task in the preparation of magnetic poly(N-isopropylacrylamide) (Fe3O4-PNIPAAm) nanocomposites for bio-applications is to maximise their reactivity and stability. Emulsion polymerisation, in situ precipitation and physical addition were used to produce Fe3O4-PNIPAAm-1, Fe3O4-PNIPAAm-2 and Fe3O4-PNIPAAm-3, respectively. Their properties were characterised using scanning electron microscopy (morphology), zeta-potential (surface charge), thermogravimetric analysis (stability), vibrating sample magnetometry (magnetisation) and dynamic light scattering. Moreover, we investigated the antibacterial effect of each nanocomposite against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Both Fe3O4-PNIPAAm-1 and Fe3O4-PNIPAAm-2 nanocomposites displayed high thermal stability, zeta potential and magnetisation values, suggesting stable colloidal systems. Overall, the presence of Fe3O4-PNIPAAm nanocomposites, even at lower concentrations, caused significant damage to both E. coli and S. aureus DNA and led to a decrease in cell viability. Fe3O4-PNIPAAm-1 displayed a stronger antimicrobial effect against both bacterial strains than Fe3O4-PNIPAAm-2 and Fe3O4-PNIPAAm-3. Staphylococcus aureus was more sensitive than E. coli to all three magnetic PNIPAAm nanocomposites.

Rapid thermal responsive conductive hybrid cryogels with shape memory properties, photothermal properties and pressure dependent conductivity.

PubMed

Deng, Zexing; Guo, Yi; Ma, Peter X; Guo, Baolin

2018-09-15

Stimuli responsive cryogels with multi-functionality have potential application for electrical devices, actuators, sensors and biomedical devices. However, conventional thermal sensitive poly(N-isopropylacrylamide) cryogels show slow temperature response speed and lack of multi-functionality, which greatly limit their practical application. Herein we present conductive fast (2 min for both deswelling and reswelling behavior) thermally responsive poly(N-isopropylacrylamide) cryogels with rapid shape memory properties (3 s for shape recovery), near-infrared (NIR) light sensitivity and pressure dependent conductivity, and further demonstrated their applications as temperature sensitive on-off switch, NIR light sensitive on-off switch, water triggered shape memory on-off switch and pressure dependent device. These cryogels were first prepared in dimethyl sulfoxide below its melting temperature in ice bath and subsequently put into aniline or pyrrole solution to in situ deposition of conducting polyaniline or polypyrrole nanoparticles. The continuous macroporous sponge-like structure provides cryogels with rapid responsivity both in deswelling, reswelling kinetics and good elasticity. After incorporating electrically conductive polyaniline or polypyrrole nanoaggregates, the hybrid cryogels exhibit desirable conductivity, photothermal property, pressure dependent conductivity and good cytocompatibility. These multifunctional hybrid cryogels make them great potential as stimuli responsive electrical device, tissue engineering scaffolds, drug delivery vehicle and electronic skin. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of the Z- and Macro-R-Group on the Thermal Desulfurization of Polymers Synthesized with Acid/Base "Switchable" Dithiocarbamate RAFT Agents.

PubMed

Stace, Sarah J; Fellows, Christopher M; Moad, Graeme; Keddie, Daniel J

2018-05-11

Thermolysis is examined as a method for complete desulfurization of reversible addition-fragmentation chain transfer (RAFT)-synthesized polymers prepared with acid/base "switchable" N-methyl-N-pyridyldithiocarbamates [RS 2 CZ or RS 2 CZH + ]. Macro-RAFT agents from more activated monomers (MAMs) (i.e., styrene (St), N-isopropylacrylamide (NIPAm), and methyl methacrylate (MMA)) with RS 2 CZH + and less activated monomers (LAMs) (i.e., vinyl acetate (VAc) and N-vinylpyrolidone (NVP)) with RS 2 CZ are prepared by RAFT polymerization and analyzed by thermogravimetric analysis. In all cases, a mass loss consistent with loss of the end group (ZCS 2 H) is observed at temperatures lower than, and largely discrete from, that required for further degradation of the polymer. The temperatures for end group loss and the new end groups formed are strongly dependent on the identity of the R(P) n and the state of the pyridyl Z group; increasing in the series poly(MMA) < poly(St) ∼ poly(NIPAm) < poly(VAc) ∼ poly(NVP) for S 2 CZ and poly(MMA) < poly(St) ∼ poly(NIPAm) for S 2 CZH + . Clean end group removal is possible for poly(St) and poly(NVP). For poly(NIPAm), the thiocarbonyl chain end is removed, but the end group identity is less certain. For poly(MMA) and poly(VAc), some degradation of the polymer accompanies end group loss under the conditions used and further refinement of the process is required. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Thomas, Carla S.; Xu, Liza; Olsen, Bradley D.

Blending the small molecule osmolytes glycerol and trehalose with the model globular protein–polymer block copolymer mCherry-b-poly(N-isopropyl acrylamide) (mCherry-b-PNIPAM) is demonstrated to improve protein functionality in self-assembled nanostructures. The incorporation of either additive into block copolymers results in functionality retention in the solid state of 80 and 100% for PNIPAM volume fractions of 40 and 55%, respectively. This represents a large improvement over the 50–60% functionality observed in the absence of any additive. Furthermore, glycerol decreases the thermal stability of block copolymer films by 15–20 °C, while trehalose results in an improvement in the thermal stability by 15–20 °C. These resultsmore » suggest that hydrogen bond replacement is responsible for the retention of protein function but suppression or enhancement of thermal motion based on the glass transition of the osmolyte primarily determines thermal stability. While both osmolytes are observed to have a disordering effect on the nanostructure morphology with increasing concentration, this effect is less pronounced in materials with a larger polymer volume fraction. Glycerol preferentially localizes in the protein domains and swells the nanostructures, inducing disordering or a change in morphology depending on the PNIPAM coil fraction. In contrast, trehalose is observed to macrophase separate from the block copolymer, which results in nanodomains becoming more disordered without changing significantly in size.« less

Preparation of thermo-responsive polymer brushes on hydrophilic polymeric beads by surface-initiated atom transfer radical polymerization for a highly resolutive separation of peptides.

PubMed

Mizutani, Aya; Nagase, Kenichi; Kikuchi, Akihiko; Kanazawa, Hideko; Akiyama, Yoshikatsu; Kobayashi, Jun; Annaka, Masahiko; Okano, Teruo

2010-09-17

Poly(N-isopropylacrylamide-co-N-tert-butylacrylamide) [P(IPAAm-co-tBAAm)] brushes were prepared on poly(hydroxy methacrylate) (PHMA) [hydrolyzed poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate)] beads having large pores by surface-initiated atom transfer radical polymerization (ATRP) and applied to the stationary phases of thermo-responsive chromatography. Optimized amount of copolymer brushes grafted PHMA beads were able to separate peptides and proteins with narrow peaks and a high resolution. The beads were found to have a specific surface area of 43.0 m(2)/g by nitrogen gas adsorption method. Copolymer brush of P(IPAAm-co-tBAAm) grafted PHMA beads improved the stationary phase of thermo-responsive chromatography for the all-aqueous separation of peptides and proteins. 2010 Elsevier B.V. All rights reserved.

Block Copolymers and Ionic Liquids: A New Class of Functional Nanocomposites

NASA Astrophysics Data System (ADS)

Lodge, Timothy

2009-03-01

Block copolymers provide a remarkably versatile platform for achieving desired nanostructures by self-assembly, with lengthscales varying from a few nanometers up to several hundred nanometers. Ionic liquids are an emerging class of solvents, with an appealing set of physical attributes. These include negligible vapor pressure, high chemical and thermal stability, tunable solvation properties, high ionic conductivity, and wide electrochemical windows. For various applications it will be necessary to solidify the ionic liquid into particular spatial arrangements, such as membranes or gels, or to partition the ionic liquid in coexisting phases, such as microemulsions and micelles. One example includes formation of spherical, cylindrical, and vesicular micelles by poly(butadiene-b-ethylene oxide) and poly(styrene-b-methylmethacrylate) in the common hydrophobic ionic liquids [BMI][PF6] and [EMI][TFSI]. This work has been extended to the formation of reversible micelle shuttles between ionic liquids and water, whereby entire micelles transfer from one phase to the other, reversibly, depending on temperature and solvent quality. Formation of ion gels has been achieved by self-assembly of poly(styrene-b-ethylene oxide-b-styrene) triblocks in ionic liquids, and by the thermoreversible system poly(N-isopropylacrylamide-b-ethylene oxide-b-N-isopropylacrylamide), using as little as 4% copolymer. Further, these gels have been shown to be remarkably effective as gate dielectrics in organic thin film transistors. The remarkably high capacitance of the ion gels (> 10 μF/cm^2) supports a very high carrier density in an organic semiconductor such as poly(3-hexylthiophene), leading to milliamp currents for low applied voltages. Furthermore, the rapid mobility of the ions enables switching speeds approaching 10 kHz, orders of magnitude higher than achievable with other polymer-based dielectrics such as PEO/LiClO4. Finally, we have shown that ordered nanostructures of block copolymers plus ionic liquids show the characteristic self-assembly properties of strongly-segregated systems. Prospects for anisotropic ionic conductivity are also being explored.

Control the wettability of poly(n-isopropylacrylamide-co-1-adamantan-1-ylmethyl acrylate) modified surfaces: the more Ada, the bigger impact?

PubMed

Shi, Xiu-Juan; Chen, Gao-Jian; Wang, Yan-Wei; Yuan, Lin; Zhang, Qiang; Haddleton, David M; Chen, Hong

2013-11-19

Surface-initiated SET-LRP was used to synthesize polymer brush containing N-isopropylacrylamide and adamantyl acrylate using Cu(I)Cl/Me6-TREN as precursor catalyst and isopropanol/H2O as solvent. Different reaction conditions were explored to investigate the influence of different parameters (reaction time, catalyst concentration, monomer concentration) on the polymerization. Copolymers with variable 1-adamantan-1-ylmethyl acrylate (Ada) content and comparable thickness were synthesized onto silicon surfaces. Furthermore, the hydrophilic and bioactive molecule β-cyclodextrin-(mannose)7 (CDm) was synthesized and complexed with adamantane via host-guest interaction. The effect of adamantane alone and the effect of CDm together with adamantane on the wettability and thermoresponsive property of surface were investigated in detail. Experimental and molecular structure analysis showed that Ada at certain content together with CDm has the greatest impact on surface wettability. When Ada content was high (20%), copolymer-CDm surfaces showed almost no CDm complexed with Ada as the result of steric hindrance.

Polymers as directing agents for motions of chemical and biological species

NASA Astrophysics Data System (ADS)

Tanyeri, Nihan Yonet

This thesis involves descriptions of solid surface modifications with various polymeric materials which were used as a guiding agent for motion of chemical and biological species. Quasi-two dimensional poly(oligoethylene glycol) acrylate polymer brush based molecular conduits have been designed with the goal of regulating and controlling the diffusive transport of molecular, e.g. organic dyes, and ionic species, e.g. AuCl4-, and Cu2+ ions, along predefined 2-D pathways. The transport of these chemical species has been examined by both fluorescence and dark field microscopy. The polymer brushes were formed through microcontact printing of an initiator, followed by surface-initiated Atom Transfer Radical Polymerization (SI-ATRP). SI-ATRP enables both 2-D patterning with a resolution of about 1 micrometer, and control over the resultant polymer brush thickness (which was varied from 10-100 nm). A hydrophilic poly(oligoethylene glycol) acrylate brushe was selected because of its potential to dissolve a wide range of hydrophilic species. The transport of fluorescent species can be directly followed. A non-lithographic fabrication method was developed for mufluidic devices used in the diffusion studies. Singular channel mufluidic device was utilized to study the directed organic dye diffusion. The AuCl4-, and Cu 2+ ion transport was studied by designing molecular devices with two mufluidic channels. We have demonstrated that the various species of interest diffuse much more rapidly along the predefined pathway than along the bare (polymer brush free) regions of the substrate, demonstrating that diffusive conduits for molecular transport can indeed be formed. The protein resistance of poly(N-isopropylacrylamide) (PNIPAM) brushes grafted from silicon wafers was investigated as a function of the chain molecular weight, grafting density, and temperature. Above the lower critical solution temperature (LCST) of 32°C, the collapse of the water swollen chains, determined by ellipsometry, depends on the grafting density and molecular weight. Ellipsometry, radio assay, and fluorescence imaging demonstrated that, below the LCST, the brushes repel protein as effectively as oligoethylene oxide terminated monolayers. Above 32°C, very low levels of protein adsorb on densely grafted brushes, and the amounts of adsorbed protein increase with decreasing brush grafting densities. Brushes that do not exhibit a collapse transition also bind protein, even though the chains remain extended above the LCST. These findings suggest possible mechanisms underlying protein interactions with end-grafted PNIPAM brushes. 3D porous materials on solid surfaces were built to mimic the corneal basement membrane so that we can monitor direction of the corneal epithelia cells behaviors as the surface topography changes. We have used colloidal crystal templating approach to build the 3D porous structures. Polystyrene (PS) colloids were crystallized in a flow cell. The crystals were filled with acrylamide precursor (including photoinitiator, crosslinker) in the oxygen free aqueous solution. After polymerization of acrylamide under UV exposure, PS colloids were dissolved in chloroform. Thus, 3D porous polyacrylamide hydrogels have been fabricated. The various pore sizes at the 3D porous surface have been obtained by using PS colloids with the colloid diameters ranging from 450 nm to 4 mum. Human corneal epithelial cell growth, morphology change and adhesion studies have been conducted on the porous polyacrylamide scaffolds. The effect of pore size on human corneal epithelial cell function has been investigated.

Temperature- and pH-Sensitive Nanohydrogels of Poly(N-Isopropylacrylamide) for Food Packaging Applications: Modelling the Swelling-Collapse Behaviour

PubMed Central

Fuciños, Clara; Fuciños, Pablo; Míguez, Martín; Katime, Issa; Pastrana, Lorenzo M.; Rúa, María L.

2014-01-01

Temperature-sensitive poly(N-isopropylacrylamide) (PNIPA) nanohydrogels were synthesized by nanoemulsion polymerization in water-in-oil systems. Several cross-linking degrees and the incorporation of acrylic acid as comonomer at different concentrations were tested to produce nanohydrogels with a wide range of properties. The physicochemical properties of PNIPA nanohydrogels, and their relationship with the swelling-collapse behaviour, were studied to evaluate the suitability of PNIPA nanoparticles as smart delivery systems (for active packaging). The swelling-collapse transition was analyzed by the change in the optical properties of PNIPA nanohydrogels using ultraviolet-visible spectroscopy. The thermodynamic parameters associated with the nanohydrogels collapse were calculated using a mathematical approach based on the van't Hoff analysis, assuming a two-state equilibrium (swollen to collapsed). A mathematical model is proposed to predict both the thermally induced collapse, and the collapse induced by the simultaneous action of two factors (temperature and pH, or temperature and organic solvent concentration). Finally, van't Hoff analysis was compared with differential scanning calorimetry. The results obtained allow us to solve the problem of determining the molecular weight of the structural repeating unit in cross-linked NIPA polymers, which, as we show, can be estimated from the ratio of the molar heat capacity (obtained from the van't Hoff analysis) to the specific heat capacity (obtained from calorimetric measurements). PMID:24520326

Temperature- and pH-sensitive nanohydrogels of poly(N-Isopropylacrylamide) for food packaging applications: modelling the swelling-collapse behaviour.

PubMed

Fuciños, Clara; Fuciños, Pablo; Míguez, Martín; Katime, Issa; Pastrana, Lorenzo M; Rúa, María L

2014-01-01

Temperature-sensitive poly(N-isopropylacrylamide) (PNIPA) nanohydrogels were synthesized by nanoemulsion polymerization in water-in-oil systems. Several cross-linking degrees and the incorporation of acrylic acid as comonomer at different concentrations were tested to produce nanohydrogels with a wide range of properties. The physicochemical properties of PNIPA nanohydrogels, and their relationship with the swelling-collapse behaviour, were studied to evaluate the suitability of PNIPA nanoparticles as smart delivery systems (for active packaging). The swelling-collapse transition was analyzed by the change in the optical properties of PNIPA nanohydrogels using ultraviolet-visible spectroscopy. The thermodynamic parameters associated with the nanohydrogels collapse were calculated using a mathematical approach based on the van't Hoff analysis, assuming a two-state equilibrium (swollen to collapsed). A mathematical model is proposed to predict both the thermally induced collapse, and the collapse induced by the simultaneous action of two factors (temperature and pH, or temperature and organic solvent concentration). Finally, van't Hoff analysis was compared with differential scanning calorimetry. The results obtained allow us to solve the problem of determining the molecular weight of the structural repeating unit in cross-linked NIPA polymers, which, as we show, can be estimated from the ratio of the molar heat capacity (obtained from the van't Hoff analysis) to the specific heat capacity (obtained from calorimetric measurements).

Construction of a thermoresponsive magnetic porous polymer membrane enzyme reactor for glutaminase kinetics study.

PubMed

Zhao, Liping; Qiao, Juan; Moon, Meyong Hee; Qi, Li

2018-06-16

Fabrication of polymer membranes with nanopores and a confinement effect toward enzyme immobilization has been an enabling endeavor. In the work reported here, an enzyme reactor based on a thermoresponsive magnetic porous block copolymer membrane was designed and constructed. Reversible addition-fragmentation chain transfer polymerization was used to synthesize the block copolymer, poly(maleic anhydride-styrene-N-isopropylacrylamide), with poly(N-isopropylacrylamide) as the thermoresponsive moiety. The self-assembly property of the block copolymer was used for preparation of magnetic porous thin film matrices with iron oxide nanoparticles. By covalent bonding of glutaminase onto the surface of the membrane matrices and changing the temperature to tune the nanopore size, we observed enhanced enzymolysis efficiency due to the confinement effect. The apparent Michaelis-Menten constant and the maximum rate of the enzyme reactor were determined (K m = 32.3 mM, V max = 33.3 mM min -1 ) by a chiral ligand exchange capillary electrochromatography protocol with L-glutamine as the substrate. Compared with free glutaminase in solution, the proposed enzyme reactor exhibits higher enzymolysis efficiency, greater stability, and greater reusability. Furthermore, the enzyme reactor was applied for a glutaminase kinetics study. The tailored pore sizes and the thermoresponsive property of the block copolymer result in the designed porous membrane based enzyme reactor having great potential for high enzymolysis performance. Graphical abstract ᅟ.

Poly(N-isopropylacrylamide) hydrogel/chitosan scaffold hybrid for three-dimensional stem cell culture and cartilage tissue engineering.

PubMed

Mellati, Amir; Kiamahalleh, Meisam Valizadeh; Madani, S Hadi; Dai, Sheng; Bi, Jingxiu; Jin, Bo; Zhang, Hu

2016-11-01

Providing a controllable and definable three-dimensional (3D) microenvironment for chondrogenic differentiation of mesenchymal stem cells (MSCs) remains a great challenge for cartilage tissue engineering. In this work, poly(N-isopropylacrylamide) (PNIPAAm) polymers with the degrees of polymerization of 100 and 400 (NI100 and NI400) were prepared and the polymer solutions were introduced into the preprepared chitosan porous scaffolds (CS) to form hybrids (CSNI100 and CSNI400, respectively). SEM images indicated that the PNIPAAm gel partially occupied chitosan pores while the interconnected porous structure of chitosan was preserved. MSCs were incorporated within the hybrid and cell proliferation and chondrogenic differentiation were monitored. After 7-day incubation of the cell-laden constructs in a growth medium, the cell viability in CSNI100 and CSNI400 were 54 and 108% higher than that in CS alone, respectively. Glycosaminoglycan and total collagen contents increased 2.6- and 2.5-fold after 28-day culture of cell-laden CSNI400 in the chondrogenic medium. These results suggest that the hybrid structure composed of the chitosan porous scaffold and the well-defined PNIPAAm hydrogel, in particular CSNI400, is suitable for 3D stem cell culture and cartilage tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2764-2774, 2016. © 2016 Wiley Periodicals, Inc.

Epigallocatechin Gallate-Loaded Gelatin-g-Poly(N-Isopropylacrylamide) as a New Ophthalmic Pharmaceutical Formulation for Topical Use in the Treatment of Dry Eye Syndrome.

PubMed

Luo, Li-Jyuan; Lai, Jui-Yang

2017-08-24

Given that biodegradable in situ gelling delivery systems may have potential applications in the design of ophthalmic pharmaceutical formulations, this study, for the first time, aims to develop gelatin-g-poly(N-isopropylacrylamide) (GN) carriers for topical epigallocatechin gallate (EGCG) administration in the treatment of dry eye disease (DED). By temperature triggered sol-gel phase transition of copolymers, EGCG-loaded GN was prepared at 32 °C and characterized by FTIR, NMR, and HPLC analyses. Results of WST-1 and live/dead assays showed that GN materials have good compatibility with corneal epithelial cells. Gradual biodegradation of delivery carriers allowed sustained release of EGCG without drug toxicity. Anti-inflammatory and antioxidant activity studies also indicated effective therapeutic drug levels at each time point within 3 days of release. In a rabbit dry eye model, corneal epithelial defects was ameliorated by treatment with single-dose administration of EGCG-containing GN. Furthermore, drug molecules released from carrier materials could prevent further tear evaporation and loss of mucin-secreting goblet cells in diseased animals. Our findings suggest that GN carrier is responsible for enhanced pharmacological efficacy of topically instilled EGCG, thereby demonstrating the benefits of using biodegradable in situ gelling delivery system to overcome the drawbacks of limited dry eye relief associated with eye drop dosage form.

Poly(N-isopropylacrylamide)-chitosan as thermosensitive in situ gel-forming system for ocular drug delivery.

PubMed

Cao, Yanxia; Zhang, Can; Shen, Wenbin; Cheng, Zhihong; Yu, Liangli Lucy; Ping, Qineng

2007-07-31

A novel copolymer, poly(N-isopropylacrylamide)-chitosan (PNIPAAm-CS), was investigated for its thermosensitive in situ gel-forming properties and potential utilization for ocular drug delivery. The thermal sensitivity and low critical solution temperature (LCST) were determined by the cloud point method. PNIPAAm-CS had a LCST of 32 degrees C, which is close to the surface temperature of the eye. The in vivo ocular pharmacokinetics of timolol maleate in PNIPAAm-CS solution were evaluated and compared to that in conventional eye drop solution by using rabbits according to the microdialysis method. The C(max) of timolol maleate in aqueous fluid for the PNIPAAm-CS solution was 11.2 microg/ml, which is two-fold higher than that of the conventional eye drop, along with greater AUC. Furthermore, the PNIPAAm-CS gel-forming solution of timolol maleate had a stronger capacity to reduce the intra-ocular pressure (IOP) than that of the conventional eye drop of same concentration over a period of 12 h. In addition, the MTT assay showed that there is little cytotoxicity of PNIPAAm-CS at concentration range of 0.5-400 microg/ml. These results suggest that PNIPAAm-CS is a potential thermosensitive in situ gel-forming material for ocular drug delivery, and it may improve the bio-availability, efficacy, and compliance of some eye drugs.

Fabrication and characterization of thermo-responsive gold nanorod assemblies

NASA Astrophysics Data System (ADS)

Bustamante, Gilbert; Carrizales, Katherine; DeLuna, Frank; Large, Nicolas; Ye, Jing Yong

2018-02-01

Advancements in nanotechnology sensors have aided in the detection of subtle, but significant cellular deviations that may mark certain stages of diseases. Gold nanorods (GNRs) are often studied for this purpose due to their tunable optical properties and ease in surface functionalization. The absorption properties of GNRs are governed by the localized surface plasmon resonance (LSPR), which strongly depends on the GNR's aspect ratio and on interparticle interactions. By controlling the coupling of nearby rods, a sensor can be created to respond to temperature fluctuations in the local environment. Here, we fabricated thermo-responsive gold nanorod assemblies by conjugating GNRs in end-to-end or side-by-side configurations using Poly(N-isopropyl acrylamide) (PNIPAM). End-to-end assemblies were fabricated through mixture of GNRs and PNIPAM in DI water. GNRs and PNIPAM were combined in DI water and dimethylformamide (DMF) under sonication to achieve side-by-side configuration. The optical absorption of the assemblies was measured by UV-Visible spectroscopy at different temperatures. As the temperature increased, the polymer contracted and initiated plasmon coupling between the GNRs. The optical spectrum experienced a blue- or red-shift for side-by-side or end-to-end configurations, respectively. Spectral tunability reversal was observed when cooled. Experimental results were verified by finite-difference time-domain (FDTD) calculations, which demonstrated spectral shifts under similar parameters. We present methods for fabrication of thermo-responsive gold nanorods for use as a local thermal nanosensor.

Biodegradable in situ gelling delivery systems containing pilocarpine as new antiglaucoma formulations: effect of a mercaptoacetic acid/N-isopropylacrylamide molar ratio

PubMed Central

Lai, Jui-Yang

2013-01-01

Ocular drug delivery is one of the most commonly used treatment modalities in the management of glaucoma. We have recently proposed the use of gelatin and poly(N-isopropylacrylamide) (PNIPAAm) graft copolymers as biodegradable in situ forming delivery systems for the intracameral administration of antiglaucoma medications. In this study, we further investigated the influence of carrier characteristics on drug delivery performance. The carboxyl-terminated PNIPAAm samples with different molecular weights were synthesized by varying the molar ratio of mercaptoacetic acid (MAA)/N-isopropylacrylamide (NIPAAm) from 0.05 to 1.25, and were determined by end-group titration. The preparation of gelatin-g-PNIPAAm (GN) copolymers from these thermoresponsive polymers was achieved using carbodiimide chemistry. Our results showed that the carboxylic end-capped PNIPAAm of high molecular weight may lead to the lower thermal phase transition temperature and slower degradation rate of GN vehicles than its low molecular weight counterparts. With a decreasing MAA/NIPAAm molar ratio, the drug encapsulation efficiency of copolymers was increased due to fast temperature-triggered capture of pilocarpine nitrate. The degradation of the gelatin network could greatly affect the drug release profiles. All of the GN copolymeric carriers demonstrated good corneal endothelial cell and tissue compatibility. It is concluded that different types of GN-based delivery systems exhibit noticeably distinct intraocular pressure-lowering effect and miosis action, thereby reflecting the potential value of a MAA/NIPAAm molar ratio in the development of new antiglaucoma formulations. PMID:24187486

Biodegradable in situ gelling delivery systems containing pilocarpine as new antiglaucoma formulations: effect of a mercaptoacetic acid/N-isopropylacrylamide molar ratio.

PubMed

Lai, Jui-Yang

2013-01-01

Ocular drug delivery is one of the most commonly used treatment modalities in the management of glaucoma. We have recently proposed the use of gelatin and poly(N-isopropylacrylamide) (PNIPAAm) graft copolymers as biodegradable in situ forming delivery systems for the intracameral administration of antiglaucoma medications. In this study, we further investigated the influence of carrier characteristics on drug delivery performance. The carboxyl-terminated PNIPAAm samples with different molecular weights were synthesized by varying the molar ratio of mercaptoacetic acid (MAA)/N-isopropylacrylamide (NIPAAm) from 0.05 to 1.25, and were determined by end-group titration. The preparation of gelatin-g-PNIPAAm (GN) copolymers from these thermoresponsive polymers was achieved using carbodiimide chemistry. Our results showed that the carboxylic end-capped PNIPAAm of high molecular weight may lead to the lower thermal phase transition temperature and slower degradation rate of GN vehicles than its low molecular weight counterparts. With a decreasing MAA/NIPAAm molar ratio, the drug encapsulation efficiency of copolymers was increased due to fast temperature-triggered capture of pilocarpine nitrate. The degradation of the gelatin network could greatly affect the drug release profiles. All of the GN copolymeric carriers demonstrated good corneal endothelial cell and tissue compatibility. It is concluded that different types of GN-based delivery systems exhibit noticeably distinct intraocular pressure-lowering effect and miosis action, thereby reflecting the potential value of a MAA/NIPAAm molar ratio in the development of new antiglaucoma formulations.

PNIPAm grafted amino-functionalized mesoporous silica for thermo-responsive chromium elimination

NASA Astrophysics Data System (ADS)

Chang, Jeong Ho; Kim, Jinwon; Lee, Hyesun

2017-12-01

In this study, the effective elimination of Cr(VI) was achieved by thermo-responsive polymer-grafted amino-functionalized mesoporous silica (MS@APTES@PNIPAm) in aqueous solution. The MS@APTES@PNIPAm was successfully synthesized by the coupling of 3-MOP and N-isopropyl acrylamide (NIPAm) in 3-aminoproyltriethoxysilane (APTES) grafted mesoporous silica surface. The thermo-responsive elimination of Cr(VI) was demonstrated at various pH levels and at room temperature and 40 °C, respectively. The characterization of the synthesized materials was achieved by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT-IR) and nitrogen (N2) adsorption-desorption. The maximum adsorption of hexavalent chromium on MS@APTES@PNIPAm in aqueous solution was 123.8 mg g-1 at 40 °C in pH 2.5. Furthermore, the results of isotherm and kinetic experiments demonstrated that the adsorption behavior of Cr(VI) on MS@APTES@PNIPAm was well fitted to a Langmuir plot with a pseudo-second-order and intra-particle diffusion model.

Enhancing cisplatin delivery to hepatocellular carcinoma HepG2 cells using dual sensitive smart nanocomposite.

PubMed

Salimi, Farzaneh; Dilmaghani, Karim Akbari; Alizadeh, Effat; Akbarzadeh, Abolfazl; Davaran, Soodabeh

2017-07-07

Targeted entrance and accumulation of higher doses of drugs into malignant cells could help in intensification of tumor specific cytotoxicity. A dual-responsive nanogel, poly(N-isopropylacrylamide)-co-poly(N,N-(dimethylamino)ethyl methacrylate) [P(NIPAM-co-DMA)] containing N-isopropylacrylamide (NIPAM) as thermoresponsive monomer and N,N-(dimethylamino)ethyl methacrylate (DMA) as pH-responsive monomer and methylene-bis-acrylamide (MBA) as cross-linking agent, was synthesized by free radical emulsion polymerization. Cisplatin along with magnetic Fe 3 O 4 nanoparticles (MNPs) was loaded into the nanogel by physically embedding the magnetic nanoparticles into hydrogel matrix after gelation to obtain drug-loaded magnetic nanocomposite [P(NIPAM-co-DMA)/Fe 3 O 4 ]. Drug loading efficiencies and drug release profiles of cisplatin-loaded P(NIPAM-co-DMA) nanogel and P(NIPAM-co-DMA)/Fe 3 O 4 nanocomposite were evaluated in vitro for controlled drug delivery in different temperature and pH conditions. Finally, the anticancer activity of P(NIPAM-co-DMA)/Fe 3 O 4 nanocomposite on human liver HepG2 cells was evaluated. Nanogel and nanocomposite showed significantly higher (p < .05) cisplatin release at 40 °C compared to 37 °C and at pH 5.7 compared to pH 7.4, demonstrating their temperature and pH sensitivity, respectively. The cytotoxicity assay of drug free nanogel on HepG2 cell line indicated that the nanogel is biocompatible and suitable as drug carrier. Moreover, MTT assay revealed that the cisplatin-loaded nanocomposite represented significant superior cytotoxicity (p < .05) to HepG2 cells as compared with free cisplatin.

Temperature responsive hydrogel magnetic nanocomposites for hyperthermia and metal extraction applications

NASA Astrophysics Data System (ADS)

Reddy, N. Narayana; Ravindra, S.; Reddy, N. Madhava; Rajinikanth, V.; Raju, K. Mohana; Vallabhapurapu, Vijaya Srinivasu

2015-11-01

The present work deals with the development of temperature and magnetic responsive hydrogel networks based on poly (N-isopropylacrylamide)/acrylamido propane sulfonic acid. The hydrogel matrices are synthesized by polymerizing N-isopropylacrylamide (NIPAM) monomer in the presence of acrylamido propane sulphonicacid (AMPS) using a cross-linker (N,N-methylenebisacrylamide, MBA) and redox initiating system [ammonium persulphate (APS)/tetramethylethylenediamine (TMEDA)]. The magnetic nanoparticles are generated throughout the hydrogel networks using in situ method by incorporating iron ions and subsequent treatment with ammonia. A series of hydrogel-magnetic nanocomposites (HGMNC) are developed by varying AMPS composition. The synthesized hydrogel magnetic nanocomposites (HGMNC) are characterized by using Fourier Transform Infrared (FTIR) Spectroscopy, X-ray diffraction (XRD), Thermal Analyses and Electron Microscopy analysis (Scanning and Transmission Electron Microscope). The metal extraction capacities of the prepared hydrogel (HG) and hydrogel magnetic nanocomposites (HGMNC) were studied at different temperatures. The results suggest that HGMNCs have higher extraction capacity compared to HG and HG loaded iron ions. This data also reveals that the extraction of metals by hydrogel magnetic nanocomposites (HGMNCs) is higher at higher temperatures than room temperature. The prepared HGMNCs are also subjected to hyperthermia (cancer therapy) studies.

Physicochemical characteristics of Fe3O4 magnetic nanocomposites based on Poly(N-isopropylacrylamide) for anti-cancer drug delivery.

PubMed

Davaran, Soodabeh; Alimirzalu, Samira; Nejati-Koshki, Kazem; Nasrabadi, Hamid Tayef; Akbarzadeh, Abolfazl; Khandaghi, Amir Ahmad; Abbasian, Mojtaba; Alimohammadi, Somayeh

2014-01-01

Hydrogels are a class of polymers that can absorb water or biological fluids and swell to several times their dry volume, dependent on changes in the external environment. In recent years, hydrogels and hydrogel nanocomposites have found a variety of biomedical applications, including drug delivery and cancer treatment. The incorporation of nanoparticulates into a hydrogel matrix can result in unique material characteristics such as enhanced mechanical properties, swelling response, and capability of remote controlled actuation. In this work, synthesis of hydrogel nanocomposites containing magnetic nanoparticles are studied. At first, magnetic nanoparticles (Fe3O4) with an average size 10 nm were prepared. At second approach, thermo and pH-sensitive poly (N-isopropylacrylamide -co-methacrylic acid-co-vinyl pyrrolidone) (NIPAAm-MAA- VP) were prepared. Swelling behavior of co-polymer was studied in buffer solutions with different pH values (pH=5.8, pH=7.4) at 37 °C. Magnetic iron oxide nanoparticles (Fe3O4) and doxorubicin were incorporated into copolymer and drug loading was studied. The release of drug, carried out at different pH and temperatures. Finally, chemical composition, magnetic properties and morphology of doxorubicin-loaded magnetic hydrogel nanocomposites were analyzed by FT- IR, vibrating sample magnetometry (VSM), scanning electron microscopy (SEM). The results indicated that drug loading efficiency was increased by increasing the drug ratio to polymer. Doxorubicin was released more at 40 °C and in acidic pH compared to that 37 °C and basic pH. This study suggested that the poly (NIPAAm-MAA-VP) magnetic hydrogel nanocomposite could be an effective carrier for targeting drug delivery systems of anti-cancer drugs due to its temperature sensitive properties.

Temperature-responsive copolymeric hydrogel systems synthetized by ionizing radiation

NASA Astrophysics Data System (ADS)

López-Barriguete, Jesús Eduardo; Bucio, Emilio

2017-06-01

Eight different systems of hydrogel copolymers with diverse temperature responsiveness were prepared to elaborate membranes for their biomedical application. The hydrogels were synthesized using poly(N-isopropylacrylamide) (PNIPAAm) and poly(N-vinylcaprolactam) (PNVCL), which have a low critical solution temperature (LCST) close to that of the human body temperature. The networks were synthesized using gamma radiation at a dose rate of 11.2 kGy h-1, and dose of 50 kGy. The LCST of each system was measured by differential scanning calorimetry (DSC). The effect of using hydrophilic monomers of acrylic acid (AAc), methacrylic acid (MAAc), dimethyl acrylamide (DMAAm), and hydroxyethyl methacrylate (HEMA) for the copolymerization on the critical point was evaluated. Five viable systems were obtained, with the best hydrogel being that of poly(NIPAAm-co-DMAAm), which an LCST at 39.8 °C. All the samples were characterized by FTIR-ATR, DSC, TGA, X-Ray Diffraction, and SEM. The proportion of monomers during the formation of the copolymers was decisive in the displacement of the LCST.

Preparation and drug release behavior of temperature-responsive mesoporous carbons

NASA Astrophysics Data System (ADS)

Wang, Xiufang; Liu, Ping; Tian, Yong

2011-06-01

A temperature-responsive composite based on poly (N-isopropylacrylamide) (PNIPAAm) and ordered mesoporous carbons (OMCs) has been successfully prepared by a simple wetness impregnation technique. The structures and properties of the composite were characterized by infrared spectroscopy (IR), X-ray diffraction (XRD), transmission electron microscopy (TEM), N 2 sorption, thermogravimetric analysis (TG) and differential scanning calorimetry (DSC). The results showed that the inclusion of PNIPAAm had not greatly changed the basic ordered pore structure of the OMCs. Ibuprofen (IBU) was selected as model drug, and in vitro test of IBU release exhibited a temperature-responsive controlled release delivery.

A perspective on two chemometrics tools: PCA and MCR, and introduction of a new one: Pattern recognition entropy (PRE), as applied to XPS and ToF-SIMS depth profiles of organic and inorganic materials

NASA Astrophysics Data System (ADS)

Chatterjee, Shiladitya; Singh, Bhupinder; Diwan, Anubhav; Lee, Zheng Rong; Engelhard, Mark H.; Terry, Jeff; Tolley, H. Dennis; Gallagher, Neal B.; Linford, Matthew R.

2018-03-01

X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) are much used analytical techniques that provide information about the outermost atomic and molecular layers of materials. In this work, we discuss the application of multivariate spectral techniques, including principal component analysis (PCA) and multivariate curve resolution (MCR), to the analysis of XPS and ToF-SIMS depth profiles. Multivariate analyses often provide insight into data sets that is not easily obtained in a univariate fashion. Pattern recognition entropy (PRE), which has its roots in Shannon's information theory, is also introduced. This approach is not the same as the mutual information/entropy approaches sometimes used in data processing. A discussion of the theory of each technique is presented. PCA, MCR, and PRE are applied to four different data sets obtained from: a ToF-SIMS depth profile through ca. 100 nm of plasma polymerized C3F6 on Si, a ToF-SIMS depth profile through ca. 100 nm of plasma polymerized PNIPAM (poly (N-isopropylacrylamide)) on Si, an XPS depth profile through a film of SiO2 on Si, and an XPS depth profile through a film of Ta2O5 on Ta. PCA, MCR, and PRE reveal the presence of interfaces in the films, and often indicate that the first few scans in the depth profiles are different from those that follow. PRE and backward difference PRE provide this information in a straightforward fashion. Rises in the PRE signals at interfaces suggest greater complexity to the corresponding spectra. Results from PCA, especially for the higher principal components, were sometimes difficult to understand. MCR analyses were generally more interpretable.

Preparation and characterization of maleoylagarose/PNIPAAm graft copolymers and formation of polyelectrolyte complexes with chitosan.

PubMed

Ortiz, J Andrés; Matsuhiro, Betty; Zapata, Paula A; Corrales, Teresa; Catalina, Fernando

2018-02-15

A water soluble derivative in 98% yield with 23.1% incorporation of maleoyl groups was obtained by esterification of agarose with maleic anhydride. Graft copolymers were synthesized through vinyl groups of maleoylagarose with N-isopropylacrylamide using ceric ammonium nitrate or ammonium persulfate as initiator, by conventional method or microwave irradiation. High nitrogen content (4.6%) was obtained in the grafting process using ceric ammonium nitrate as initiator without microwave irradiation. Copolymers were characterized by FT-IR and NMR spectroscopies, TGA, DSC and morphological analysis by AFM and SEM microscopy, confirming the grafting of PNIPAAm onto polysaccharide backbone. Hydrogel films were obtained by ionic complexation between opposite charged groups of maleoylagarose-g-poly(N-isopropylacrylamide) and chitosan. The swelling of 1:1w/v maleoylagarose-g-PNIPAAm:chitosan film was higher than 2:1w/v film at 25 and 37°C. 53% release in vitro of diclofenac sodium from 1:1w/v maleoylagarose-g-PNIPAAm:chitosan was obtained at 37°C and pH 6.0 with <0.5 diffusional constant values. Copyright © 2017 Elsevier Ltd. All rights reserved.

Preparation of a thermoresponsive polymer grafted polystyrene monolithic capillary for the separation of bioactive compounds.

PubMed

Koriyama, Takuya; Asoh, Taka-Aki; Kikuchi, Akihiko

2016-11-01

To develop aqueous microseparation columns for bioactive compounds, a thermoresponsive polymer grafted polymer monolith was prepared inside silica capillaries having an I.D. of 100μm by polymerization of styrene (St) with m/p-divinylbenzene (DVB) in the presence of polydimethylsiloxane as porogen, followed by surface-initiated atom transfer radical polymerization (SI-ATRP) of N-isopropylacrylamide (NIPAAm). SEM analysis indicated that the resulting poly(N-isopropylacrylamide) (PNIPAAm) grafted polystyrene monolith had a consecutive three-dimensionally interconnected structure and through-pores, similar to the base polystyrene (PSt) monolith. The elution behavior of steroids with different hydrophobicity was evaluated using micro-high-performance liquid chromatography in sole aqueous mobile phase. Temperature dependent interaction changes were observed between steroids and the PNIPAAm modified surfaces. Furthermore, the interaction between bioactive compounds and the PNIPAAm grafted PSt surfaces was controlled and eventually separate these molecules with different hydrophobicities by simple temperature modulation in aqueous environment. The PNIPAAm grafted PSt monolithic capillary showed improved separation properties of bioactive compounds, compared with a PNIPAAm grafted hollow capillary in aqueous environment. Copyright © 2016 Elsevier B.V. All rights reserved.

Characterization of temperature and pH-responsive poly-N-isopropylacrylamide-co-polymer nanoparticles for the release of antimicrobials

NASA Astrophysics Data System (ADS)

Hill, Laura E.; Gomes, Carmen L.

2014-09-01

Chitosan and alginate are both pH-responsive biopolymers extracted from crustacean exoskeletons and brown algae, respectively. Poly-N-isopropylacrylamide (PNIPAAM) is a hydrogel that becomes hydrophobic at a lower-critical solution temperature. This study sought to combine pH- and temperature-responsive polymers via crosslinking, in order to create a dual-stimuli responsive polymer for hydrophobic antimicrobial compounds delivery, improving their antimicrobial effects. Cinnamon bark extract (CBE) was used as a model for hydrophobic antimicrobial. Two co-polymers were synthesized to create two nanoparticles types: chitosan-co-PNIPAAM and alginate-co-PNIPAAM. Nanoparticles were formed from the resulting co-polymers using a self-assembly top-down process followed by glutaraldehyde or calcium chloride crosslinking. These nanoparticles were then used as controlled delivery vehicles for CBE, whose rapid release could be triggered by specific external stimuli. For the same pH and temperature conditions, the chitosan-co-PNIPAAM nanoparticles were significantly more potent bacterial inhibitors against both pathogens and also exhibited a faster CBE release over time as well as slightly higher entrapment efficiency. The alginate-co-PNIPAAM nanoparticles were significantly smaller and exhibited a slow, gradual release over a long time period. Although both nanoparticles were able to effectively inhibit pathogen growth at lower (P < 0.05) concentration than free CBE, the chitosan-co-PNIPAAM nanoparticles were more effective in delivering a natural antimicrobial with controlled release against foodborne pathogens.

Surface sulfonamide modification of poly(N-isopropylacrylamide)-based block copolymer micelles to alter pH and temperature responsive properties for controlled intracellular uptake.

PubMed

Cyphert, Erika L; von Recum, Horst A; Yamato, Masayuki; Nakayama, Masamichi

2018-06-01

Two different surface sulfonamide-functionalized poly(N-isopropylacrylamide)-based polymeric micelles were designed as pH-/temperature-responsive vehicles. Both sulfadimethoxine- and sulfamethazine-surface functionalized micelles were characterized to determine physicochemical properties, hydrodynamic diameters, zeta potentials, temperature-dependent size changes, and lower critical solution temperatures (LCST) in both pH 7.4 and 6.8 solutions (simulating both physiological and mild low pH conditions), and tested in the incorporation of a proof-of-concept hydrophobic antiproliferative drug, paclitaxel. Cellular uptake studies were conducted using bovine carotid endothelial cells and fluorescently labeled micelles to evaluate if there was enhanced cellular uptake of the micelles in a low pH environment. Both variations of micelles showed enhanced intracellular uptake under mildly acidic (pH 6.8) conditions at temperatures slightly above their LCST and minimal uptake at physiological (pH 7.4) conditions. Due to the less negative zeta potential of the sulfamethazine-surface micelles compared to sulfadimethoxine-surface micelles, and the proximity of their LCST to physiological temperature (37°C), the sulfamethazine variation was deemed more amenable for clinically relevant temperature and pH-stimulated applications. Nevertheless, we believe both polymeric micelle variations have the capacity to be implemented as an intracellular drug or gene delivery system in response to mildly acidic conditions. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1552-1560, 2018. © 2018 Wiley Periodicals, Inc.

Fabricating core (Au)-shell (different stimuli-responsive polymers) nanoparticles via inverse emulsion polymerization: Comparing DOX release behavior in dark room and under NIR lighting.

PubMed

Mazloomi-Rezvani, Mahsa; Salami-Kalajahi, Mehdi; Roghani-Mamaqani, Hossein

2018-06-01

Different core-shell nanoparticles with Au as core and stimuli-responsive polymers such as poly(acrylic acid) (PAA), poly(methacrylic acid) (PMAA), poly(N-isopropylacrylamide) (PNIPAAm), poly(N,N'-methylenebis(acrylamide)) (PMBA), poly(2-hydroxyethyl methacrylate) (PHEMA) and poly((2-dimethylamino)ethyl methacrylate) (PDMAEMA) as shells were fabricated via inverse emulsion polymerization. Dynamic light scattering (DLS) was used to investigate particles sizes and particle size distributions and transmission electron microscopy (TEM) was applied to observe the core-shell structure of Au-polymer nanoparticles. Also, surface charge of all samples was studied by measurement of zeta potentials. Synthesized core-shell nanoparticles were utilized as nanocarriers of DOX as anti-cancer drug and drug release behaviors were investigated in dark room and under irradiation of near-infrared (NIR) light. Results showed that all core-shell samples have particle sizes less than 100 nm with narrow particle size distributions. Moreover, amount of drug loading decreased by increasing zeta potential. In dark room, lower pH resulted in higher cumulative drug release due to better solubility of DOX in acidic media. Also, NIR lighting on DOX-loaded samples led to increasing cumulative drug release significantly. However, DOX-loaded Au-PAA and Au-PMAA showed higher drug release at pH = 7.4 compared to 5.3 under NIR lighting. Copyright © 2018 Elsevier B.V. All rights reserved.

Synthesis and Characterization of pH and Thermo Dual-Responsive Hydrogels with a Semi-IPN Structure Based on N-Isopropylacrylamide and Itaconamic Acid.

PubMed

Rwei, Syang-Peng; Tuan, Huynh Nguyen Anh; Chiang, Whe-Yi; Way, Tun-Fun

2018-04-28

A series of semi-interpenetrating polymer network (semi-IPN) hydrogels were synthesized and investigated in this study. Linear copolymer poly( N -isopropylacrylamide-co-itaconamic acid) p(NIPAM-co-IAM), which is formed by copolymerization of N -isopropylacrylamide (NIPAM) and itaconamic acid (IAM, 4-amino-2-ethylene-4-oxobutanoic acid), was introduced into a solution of NIPAM to form a series of pH and thermo dual-responsive p(NIPAM-co-IAM)/pNIPAM semi-IPN hydrogels by free radical polymerization. The structural, morphological, chemical, and physical properties of the linear copolymer and semi-IPN hydrogels were investigated. The semi-IPN hydrogel showed high thermal stability according to thermal gravimetric analyzer (TGA). Scanning electronic microscopy (SEM) images showed that the pore size was in the range of 119~297 µm and could be controlled by the addition ratio of the linear copolymer in the semi-IPN structure. The addition of linear copolymer increased the fracture strain from 57.5 ± 2.9% to 91.1 ± 4.9% depending on the added amount, while the compressive modulus decreased as the addition increased. Moreover, the pH and thermo dual-responsive properties were investigated using differential scanning calorimetry (DSC) and monitoring the swelling behavior of the hydrogels. In deionized (DI) water, the equilibrium swelling ratio of the hydrogels decreased as the temperature increased from 20 °C to 50 °C, while it varied in various pH buffer solutions. In addition, the swelling and deswelling rates of the hydrogels also significantly increased. The results indicate that the novel pH-thermo dual-responsive semi-IPN hydrogels were synthesized successfully and may be a potential material for biomedical, drug delivery, or absorption application.

Multifunctional Core–Shell Nanoparticles: Discovery of Previously Invisible Biomarkers

PubMed Central

2011-01-01

Many low-abundance biomarkers for early detection of cancer and other diseases are invisible to mass spectrometry because they exist in body fluids in very low concentrations, are masked by high-abundance proteins such as albumin and immunoglobulins, and are very labile. To overcome these barriers, we created porous, buoyant, core–shell hydrogel nanoparticles containing novel high affinity reactive chemical baits for protein and peptide harvesting, concentration, and preservation in body fluids. Poly(N-isopropylacrylamide-co-acrylic acid) nanoparticles were functionalized with amino-containing dyes via zero-length cross-linking amidation reactions. Nanoparticles functionalized in the core with 17 different (12 chemically novel) molecular baits showed preferential high affinities (KD < 10–11 M) for specific low-abundance protein analytes. A poly(N-isopropylacrylamide-co-vinylsulfonic acid) shell was added to the core particles. This shell chemistry selectively prevented unwanted entry of all size peptides derived from albumin without hindering the penetration of non-albumin small proteins and peptides. Proteins and peptides entered the core to be captured with high affinity by baits immobilized in the core. Nanoparticles effectively protected interleukin-6 from enzymatic degradation in sweat and increased the effective detection sensitivity of human growth hormone in human urine using multiple reaction monitoring analysis. Used in whole blood as a one-step, in-solution preprocessing step, the nanoparticles greatly enriched the concentration of low-molecular weight proteins and peptides while excluding albumin and other proteins above 30 kDa; this achieved a 10,000-fold effective amplification of the analyte concentration, enabling mass spectrometry (MS) discovery of candidate biomarkers that were previously undetectable. PMID:21999289

Implications of poly(N-isopropylacrylamide)-g-poly(ethylene glycol) with codissolved brain-derived neurotrophic factor injectable scaffold on motor function recovery rate following cervical dorsolateral funiculotomy in the rat

PubMed Central

Grous, Lauren Conova; Vernengo, Jennifer; Jin, Ying; Himes, B. Timothy; Shumsky, Jed S.; Fischer, Itzhak; Lowman, Anthony

2016-01-01

Object In a follow-up study to their prior work, the authors evaluated a novel delivery system for a previously established treatment for spinal cord injury (SCI), based on a poly(N-isopropylacrylamide) (PNIPAAm), lightly cross-linked with a polyethylene glycol (PEG) injectable scaffold. The primary aim of this work was to assess the recovery of both spontaneous and skilled forelimb function following a cervical dorsolateral funiculotomy in the rat. This injury ablates the rubrospinal tract (RST) but spares the dorsal and ventral corticospinal tract and can severely impair reaching and grasping abilities. Methods Animals received an implant of either PNIPAAm-g-PEG or PNIPAAm-g-PEG + brain-derived neurotrophic factor (BDNF). The single-pellet reach-to-grasp task and the staircase-reaching task were used to assess skilled motor function associated with reaching and grasping abilities, and the cylinder task was used to assess spontaneous motor function, both before and after injury. Results Because BDNF can stimulate regenerating RST axons, the authors showed that animals receiving an implant of PNIPAAm-g-PEG with codissolved BDNF had an increased recovery rate of fine motor function when compared with a control group (PNIPAAm-g-PEG only) on both a staircase-reaching task at 4 and 8 weeks post-SCI and on a single-pellet reach-to-grasp task at 5 weeks post-SCI. In addition, spontaneous motor function, as measured in the cylinder test, recovered to preinjury values in animals receiving PNIPAAm-g-PEG + BDNF. Fluorescence immunochemistry indicated the presence of both regenerating axons and BDA-labeled fibers growing up to or within the host-graft interface in animals receiving PNIPAAm-g-PEG + BDNF. Conclusions Based on their results, the authors suggest that BDNF delivered by the scaffold promoted the growth of RST axons into the lesion, which may have contributed in part to the increased recovery rate. PMID:23581453

Novel thermoresponsive assemblies of co-grafted natural and synthetic polymers for water purification.

PubMed

Paneysar, Joginder Singh; Barton, Stephen; Chandra, Sudeshna; Ambre, Premlata; Coutinho, Evans

2017-03-01

Water contamination and its purification are a global problem. The current approach to purify water is reduction of impurities to acceptable levels. One of the ways to achieve this is by use of water-soluble polymers that extract organic and metallic contaminants, from water. This paper presents a blend of composite polymers that eliminates both the contaminants simultaneously by the principle of adsorption at lower critical solution temperature. These composite polymers have been synthesized by grafting poly(N,N-diethylacrylamide), poly(N-isopropylacrylamide) and poly(N-vinylcaprolactam) on-to the natural polymer chitosan or its derivatives, giving smart graft polymeric assemblies (GPAs). One of the graft polymers, GPA-2, exhibits excellent adsorption properties able to remove metal ions like cadmium, cobalt, copper, lead, iron and also organic impurities like chlorophenol and phthalic anhydride. Studies reveal that 6 mg/ml GPA-2 is able to effect a 100% removal of organic impurities - chlorophenol (50 ppm) and phthalic anhydride (70 ppm) - from water, while complete removal of the heavy metal ions (Cu +2 , Co +2 and Cd +2 ) together at 30 ppm concentration has been achieved with 7.5 mg/ml GPA-2. The reduction in level of impurities along with recyclability and reproducibility in the elimination spectrum makes these assemblies promising materials in water treatment.

In Situ Integration of Ultrathin PtCu Nanowires with Reduced Graphene Oxide Nanosheets for Efficient Electrocatalytic Oxygen Reduction.

PubMed

Yan, Xiaoxiao; Chen, Yifan; Deng, Sihui; Yang, Yifan; Huang, Zhenna; Ge, Cunwang; Xu, Lin; Sun, Dongmei; Fu, Gengtao; Tang, Yawen

2017-11-27

Ultrathin Pt-based nanowires are considered as promising electrocatalysts owing to their high atomic utilization efficiency and structural robustness. Moreover, integration of Pt-based nanowires with graphene oxide (GO) could further increase the electrocatalytic performance, yet remains challenging to date. Herein, for the first time we demonstrate the in situ synthesis of ultrathin PtCu nanowires grown over reduced GO (PtCu-NWs/rGO) by a one-pot hydrothermal approach with the aid of amine-terminated poly(N-isopropyl acrylamide) (PNIPAM-NH 2 ). The judicious selection of PNIPAM-NH 2 facilitates the in situ nucleation and anisotropic growth of nanowires on the rGO surface and oriented attachment mechanism accounts for the formation of PtCu ultrathin nanowires. Owing to the synergy between PtCu NWs and rGO support, the PtCu-NWs/rGO outperforms the rGO supported PtCu nanoparticles (PtCu-NPs/rGO), PtCu-NWs, and commercial Pt/C toward the oxygen reduction reaction (ORR) with higher activity and better stability, making it a promising cathodic electrocatalyst for both fuel cells and metal-air cells. Moreover, the present synthetic strategy could inspire the future design of other metal alloy nanowires/carbon hybrid catalysts. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rheology of Poly(N-isopropylacrylamide)-Clay Nanocomposite Hydrogels

NASA Astrophysics Data System (ADS)

Lombardi, Jack; Xu, Di; Bhatnagar, Divya; Gersappe, Dilip; Sokolov, Jonathan; Rafailovich, Miriam

2015-03-01

The stiffness of PNIPA Gels has been reported could be significant improved by gelation with clay fillers. Here we conducted systematic rheology study of synthesized PNIPA-Clay Composites at different clay concentration, in a range from fluid to strong gel, where G'' dominant changed to G' dominant. Molecular dynamics simulation was employed to analyze the structure of composites and corresponding mechanical changes with increased clays. Where we found viscoelastic behavior become significant only 1.5 times above percolation threshold. The yield stress extrapolated from our rheology results shows good fitting to modified Mooney's theory of suspension viscosity.

Modular microfluidic valve structures based on reversible thermoresponsive ionogel actuators.

PubMed

Benito-Lopez, Fernando; Antoñana-Díez, Marta; Curto, Vincenzo F; Diamond, Dermot; Castro-López, Vanessa

2014-09-21

This paper reports for the first time the use of a cross-linked poly(N-isopropylacrylamide) ionogel encapsulating the ionic liquid 1-ethyl-3-methylimidazolium ethyl sulphate as a thermoresponsive and modular microfluidic valve. The ionogel presents superior actuation behaviour to its equivalent hydrogel. Ionogel swelling and shrinking mechanisms and kinetics are investigated as well as the performance of the ionogel when integrated as a valve in a microfluidic device. The modular microfluidic valve demonstrates fully a reversible on-off behaviour without failure for up to eight actuation cycles and a pressure resistance of 1100 mbar.

Spatially controlled, in situ synthesis of polymers

DOEpatents

Caneba, Gerard T.; Tirumala, Vijaya Raghavan; Mancini, Derrick C.; Wang, Hsien-Hau

2005-03-22

An in situ polymer microstructure formation method. The monomer mixture is polymerized in a solvent/precipitant through exposure to ionizing radiation in the absence any chemical mediators. If an exposure mask is employed to block out certain regions of the radiation cross section, then a patterned microstructure is formed. The polymerization mechanism is based on the so-called free-radical retrograde-precipitation polymerization process, in which polymerization occurs while the system is phase separating above the lower critical solution temperature. This method was extended to produce a crosslinked line grid-pattern of poly (N-isopropylacrylamide), which has been known to have thermoreversible properties.

Surface design with self-heating smart polymers for on-off switchable traps

NASA Astrophysics Data System (ADS)

Techawanitchai, Prapatsorn; Yamamoto, Kazuya; Ebara, Mitsuhiro; Aoyagi, Takao

2011-08-01

We have developed a novel self-heating, temperature-responsive chromatography system for the effective separation of biomolecules. Temperature-responsive poly(N-isopropylacrylamide-co-N-hydroxymethylacrylamide), poly(NIPAAm-co-HMAAm), was covalently grafted onto the surface of magnetite/silica composites as 'on-off' switchable surface traps. The lower critical solution temperature (LCST) of the poly(NIPAAm-co-HMAAm)s was controlled from 35 to 55 °C by varying the HMAAm content. Using the heat generated by magnetic particles in an alternating magnetic field (AMF) we were able to induce the hydrophilic to hydrophobic phase separation of the grafted temperature-responsive polymers. To assess the feasibility of the poly(NIPAAm-co-HMAAm)-grafted magnetite/silica particles as the stationary phase for chromatography, we packed the particles into the glass column of a liquid chromatography system and analyzed the elusion profiles for steroids. The retention time for hydrophobic steroids markedly increased in the AMF, because the hydrophobic interaction was enhanced via self-heating of the grafted magnetite/silica particles, and this effect could be controlled by changing the AMF irradiation time. Turning off the AMF shortened the total analysis time for steroids. The proposed system is useful for separating bioactive compounds because their elution profiles can be easily controlled by an AMF.

Comment on "Relating side chain organization of PNIPAm with its conformation in aqueous methanol" by D. Mukherji, M. Wagner, M. D. Watson, S. Winzen, T. E. de Oliveira, C. M. Marques and K. Kremer, Soft Matter, 2016, 12, 7995.

PubMed

van der Vegt, Nico F A; Rodríguez-Ropero, Francisco

2017-03-22

In a recent paper, Mukherji et al. describe the collapse of poly(N-isopropyl acrylamide) in methanol-water mixtures based on experiments and molecular dynamics simulations. The conclusion of their work is that chain collapse is dominated by enthalpic bridging interactions while entropic effects play no major role. Here we show that this claim arises from an improper interpretation of preferential binding and the corresponding thermodynamic data presented. When interpreted correctly, the data instead provide evidence for repulsive enthalpic interactions of methanol with the polymer, supporting the emerging view of entropic chain collapse.

Optimization of synthesis process of thermally-responsive poly-n-isopropylacrylamide nanoparticles for controlled release of antimicrobial hydrophobic compounds

NASA Astrophysics Data System (ADS)

Hill, Laura E.; Gomes, Carmen L.

2014-12-01

The goal of this study was to develop an effective method to synthesize poly-n-isopropylacrylamide (PNIPAAM) nanoparticles with entrapped cinnamon bark extract (CBE) to improve its delivery to foodborne pathogens and control its release with temperature stimuli. CBE was used as a model for hydrophobic natural antimicrobials. A top-down procedure using crosslinked PNIPAAM was compared to a bottom-up procedure using NIPAAM monomer. Both processes relied on self-assembly of the molecules into micelles around the CBE at 40 °C. Processing conditions were compared including homogenization time of the polymer, hydration time prior to homogenization, lyophilization, and the effect of particle ultrafiltration. The top-down versus bottom-up synthesis methods yielded particles with significantly different characteristics, especially their release profiles and antimicrobial activities. The synthesis methods affected particle size, with the bottom-up procedure resulting in smaller (P < 0.05) diameters than the top-down procedure. The controlled release profile of CBE from nanoparticles was dependent on the release media temperature. A faster, burst release was observed at 40 °C and a slower, more sustained release was observed at lower temperatures. PNIPAAM particles containing CBE were analyzed for their antimicrobial activity against Salmonella enterica serovar Typhimurium LT2 and Listeria monocytogenes Scott A. The PNIPAAM particles synthesized via the top-down procedure had a much faster release, which led to a greater (P < 0.05) antimicrobial activity. Both of the top-down nanoparticles performed similarly, therefore the 7 min homogenization time nanoparticles would be the best for this application, as the process time is shorter and little improvement was seen by using a slightly longer homogenization.

N-Isopropylacrylamide-co-glycidylmethacrylate as a Thermoresponsive Substrate for Corneal Endothelial Cell Sheet Engineering

PubMed Central

Madathil, Bernadette K.; Anil Kumar, Pallickaveedu RajanAsari; Kumary, Thrikkovil Variyath

2014-01-01

Endothelial keratoplasty is a recent shift in the surgical treatment of corneal endothelial dystrophies, where the dysfunctional endothelium is replaced whilst retaining the unaffected corneal layers. To overcome the limitation of donor corneal shortage, alternative use of tissue engineered constructs is being researched. Tissue constructs with intact extracellular matrix are generated using stimuli responsive polymers. In this study we evaluated the feasibility of using the thermoresponsive poly(N-isopropylacrylamide-co-glycidylmethacrylate) polymer as a culture surface to harvest viable corneal endothelial cell sheets. Incubation below the lower critical solution temperature of the polymer allowed the detachment of the intact endothelial cell sheet. Phase contrast and scanning electron microscopy revealed the intact architecture, cobble stone morphology, and cell-to-cell contact in the retrieved cell sheet. Strong extracellular matrix deposition was also observed. The RT-PCR analysis confirmed functionally active endothelial cells in the cell sheet as evidenced by the positive expression of aquaporin 1, collagen IV, Na+-K+ ATPase, and FLK-1. Na+-K+ ATPase protein expression was also visualized by immunofluorescence staining. These results suggest that the in-house developed thermoresponsive culture dish is a suitable substrate for the generation of intact corneal endothelial cell sheet towards transplantation for endothelial keratoplasty. PMID:25003113

Molecularly designed water soluble, intelligent, nanosize polymeric carriers.

PubMed

Pişkin, Erhan

2004-06-11

Intelligent polymers, also referred as "stimuli-responsive polymers" undergo strong property changes (in shape, surface characteristics, solubility, etc.) when only small changes in their environment (changes in temperature, pH, ionic strength light, electrical and magnetic field, etc.). They have been used in several novel applications, drug delivery systems, tissue engineering scaffolds, bioseparation, biomimetic actuators, etc. The most popular member of these type of polymers is poly(N-isopropylacrylamide) (poly(NIPA)) which exhibits temperature-sensitive character, in which the polymer chains change from water-soluble coils to water-insoluble globules in aqueous solution as temperature increases above the lower critical solution temperature (LCST) of the polymer. Copolymerization of NIPA with acrylic acid (AAc) allows the synthesis of both pH and temperature-responsive copolymers. This paper summarizes some of our related studies in which NIPA and its copolymers were synthesized and used as intelligent carriers in diverse applications.

Thio-amide functionalized polymers via polymerization or post-polymerization modification

NASA Astrophysics Data System (ADS)

Ozcam, Ali; Henke, Adam; Stibingerova, Iva; Srogl, Jiri; Genzer, Jan

2011-03-01

Decreasing supplies of fresh water and increasing population necessitates development of advanced water cleaning technologies, which would facilitate the removal of water pollutants. Amongst the worst of such contaminants are heavy metals and cyanides, infamous for their high toxicity. To assist the water purification processes, we aim to synthesize functionalized macromolecules that would contribute in the decontamination processes by scavenging detrimental chemicals. Epitomizing this role thio-amide unit features remarkable chemical flexibility that facilitates reversible catch-release of the ions, where the behavior controlled by subtle red-ox changes in the environment. Chemical tunability of the thio-amide moiety enables synthesis of thio-amide based monomers and post-polymerization modification agents. Two distinct synthetic pathways, polymerization and post-polymerization modification, have been exploited, leading to functional thioamide-based macromolecules: thioamide-monomers were copolymerized with N-isopropylacrylamide and post-polymerization modifications of poly(dimethylaminoethyl methacrylate) and poly(propargyl methacrylate) were accomplished via quarternization and ``click'' reactions, respectively.

Collapse in two good solvents, swelling in two poor solvents: defying the laws of polymer solubility?

NASA Astrophysics Data System (ADS)

Mukherji, Debashish; Marques, Carlos M.; Kremer, Kurt

2018-01-01

In this work we discuss two mirror but distinct phenomena of polymer paradoxical properties in mixed solvents: co-non-solvency and co-solvency. When a polymer collapses in a mixture of two miscible good solvents the phenomenon is known as co-non-solvency, while co-solvency is a phenomenon that is associated with the swelling of a polymer in poor solvent mixtures. A typical example of co-non-solvency is provided by poly(N-isopropylacrylamide) in aqueous alcohol, while poly(methyl methacrylate) in aqueous alcohol shows co-solvency. We discuss these two phenomena to compare their microscopic origins and show that both can be understood within generic universal concepts. A broad range of polymers is therefore expected to exhibit these phenomena where specific chemical details play a lesser role than the appropriate combination of interactions between the trio of molecular components.

Graphical analysis for gel morphology II. New mathematical approach for stretched exponential function with β>1

NASA Astrophysics Data System (ADS)

Hashimoto, Chihiro; Panizza, Pascal; Rouch, Jacques; Ushiki, Hideharu

2005-10-01

A new analytical concept is applied to the kinetics of the shrinking process of poly(N-isopropylacrylamide) (PNIPA) gels. When PNIPA gels are put into hot water above the critical temperature, two-step shrinking is observed and the secondary shrinking of gels is fitted well by a stretched exponential function. The exponent β characterizing the stretched exponential is always higher than one, although there are few analytical concepts for the stretched exponential function with β>1. As a new interpretation for this function, we propose a superposition of step (Heaviside) function and a new distribution function of characteristic time is deduced.

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

Gasser, U., E-mail: urs.gasser@psi.ch; Hyatt, J. S.; Lietor-Santos, J.-J.

We study the form factor of thermoresponsive microgels based on poly(N-isopropylacrylamide) at high generalized volume fractions, ζ, where the particles must shrink or interpenetrate to fit into the available space. Small-angle neutron scattering with contrast matching techniques is used to determine the particle form factor. We find that the particle size is constant up to a volume fraction roughly between random close packing and space filling. Beyond this point, the particle size decreases with increasing particle concentration; this decrease is found to occur with little interpenetration. Noteworthily, the suspensions remain liquid-like for ζ larger than 1, emphasizing the importance ofmore » particle softness in determining suspension behavior.« less

Thermally tunable grating using thermo-responsive magnetic fluid

NASA Astrophysics Data System (ADS)

Zaibudeen, A. W.; Philip, John

2017-04-01

We report a thermally tunable grating prepared using poly(N-isopropylacrylamide) and super paramagnetic iron oxide nanoparticles. The array spacing is reversibly tuned by varying the temperature between 5 and 38 °C. Here, the ability of thermo-responsive polymer brushes to alter their conformation at an interface is exploited to control the grating spacing in nanoscale. The underlying mechanism for the temperature dependent conformational changes are studied by measuring the subtle intermolecular forces between the polymer covered interfaces. It is observed that the interparticle forces are repulsive and exponentially decaying with distance. The thermo-responsive grating is simple to use and offers a wide range of applications.

Functionalization of chitosan by click chemistry

NASA Astrophysics Data System (ADS)

Cheaburu-Yilmaz, Catalina Natalia; Karavana, Sinem Yaprak; Yilmaz, Onur

2017-12-01

Chitosan modification represents a challenge nowadays. The variety of compounds which can be obtained with various architectures and different functionalities made it attractive to be used in fields like pharmacy and material science. Presents study deals with the chemical modification of chitosan by using click chemistry technique. The study adopted the approach of clicking azidated chitosan with a synthesized alkyne terminated polymer i.e. poly N isopropylacrylamide with thermoresponsive properties. Structures were confirmed by the FT-IR and HNMR spectra. Thermal characterization was performed showing different thermal behaviour with the chemical modification. The final synthesized graft copolymer can play important role within pharmaceutical formulations carrying drugs for topical or oral treatments.

Investigating Langmuir films at the air-water interface using a planar array infrared reflection-absorption spectrograph

NASA Astrophysics Data System (ADS)

Kim, Young Shin

In this work, a new planar array infrared reflection-absorption spectrograph (PA-IRRAS) was developed to investigate a broad range of Langmuir films at the air-water interface. This instrument is capable of recording sample and reference spectra simultaneously with an optical setup that is the same as that of a single-beam instrument but splits the incident infrared beam into two sections on a plane mirror (H) or a water trough. With this design, the instrument could accommodate large infrared accessories, such as a water trough. In addition, water bands were subtracted to obtain a high quality spectrum for a poly(lactic acid) (PLA) Langmuir film on the water subphase with a resolution of about 8 cm-1 in 10.8 sec. With this instrument, two types of monolayer systems were studied; polymeric and lipid Langmuir films at the air-water interface. For the polymeric monolayer system, PA-IRRAS was used as a probe to follow the real-time conformational changes associated with intermolecular interactions of the polymer chains during the compression of the monolayers. It was found that the mixture of poly(D-lactic acid) (PDLA) and poly(L-lactic acid) (PLLA) (D/L) formed a stereocomplex when the mixed solution developed the two-dimensional monolayer at the air-water interface. The stereocomplexation occurred before film compression, indicating that there is no direct correlation between film compression and stereocomplexation. For the lipid monolayer system, PA-IRRAS was also used as a probe to investigate the origin of the disruption of a lipid monolayer upon protein adsorption at the air-water interface. Analysis of the time-resolved PA-IRRAS spectra revealed that Cu(II) ion-chelated DSIDA lipid monolayer (Cu 2+-DSIDA) was readily disrupted by myoglobin adsorption as demonstrated by a blue shift of 1.7 cm-1 and a lower intensity in the vas(CH2) stretch mode of the lipid monolayer over a period of five hours. To find the origin of the disruption of the lipid monolayer, a postulated model, employing a DSIDA monolayer-deposited ZnSe window, was investigated. An FT-IR spectroscopic study demonstrated that the Cu(II) ion formed stronger chelation with an iminodiacetatic acid (IDA) lipid head group than that formed with a Zn(II) ion. In addition, no distinct difference was observed in the secondary structures of myoglobin as myoglobin was adsorbed to Cu2+-DSIDA over a period of five hours. Dynamic light scattering (DLS) data revealed that, by the addition of Cu(II) or Zn(II) ion, lysozyme was rapidly aggregated and readily precipitated. However, the hydrodynamic volume of myoglobin was not responsive to the addition of Zn(II) ion. When Cu(II) ion was added, aggregation of myoglobin was sustained without precipitation over a period of five hours. Therefore, these results strongly suggest that the disruption of Cu2+-DSIDA lipid monolayer upon myoglobin adsorption is due to myoglobin aggregation, mediated by the chelated Cu(II) ion, rather than a conformational change in adsorbed myoglobin. Besides the above monolayer systems, PA-IRRAS is used for the rapid detection of a low concentration of aqueous species. The previous designs for a PA-IR spectrograph were not applicable to detect a low concentration of aqueous species due to the contribution from a stray light and high relative humidity (in the vicinity of 25-40%). To overcome this problem, newly designed PA-IRRAS optical setup was purged with dry nitrogen gas to keep the relative humidity at approximately 15%. In addition, baffles constructed from corrugated cardboard were placed throughout the optical setup to prevent any stray light from reaching the detector. The PA-IRRAS results obtained from poly(N-isopropylacrylamide) (PNIPAM) revealed that solutions down to a concentration of 0.005% w/w could be successfully studied. These results are quite remarkable, given the acquisition time of only 10 seconds and the direct overlap of the Amide I band of PNIPAM and the H-O-H stretch of H2O. (Abstract shortened by UMI.)

Poly(Ionic Liquid) Semi-Interpenetrating Network Multi-Responsive Hydrogels

PubMed Central

Tudor, Alexandru; Florea, Larisa; Gallagher, Simon; Burns, John; Diamond, Dermot

2016-01-01

Herein we describe poly(ionic liquid) hydrogel actuators that are capable of responding to multiple stimuli, namely temperature, ionic strength and white light irradiation. Using two starting materials, a crosslinked poly ionic liquid (PIL) and a linear poly(N-isopropylacrylamide-co-spiropyran-co-acrylic acid), several semi-interpenetrating (sIPN) hydrogels were synthesised. The dimensions of hydrogels discs were measured before and after applying the stimuli, to quantify their response. Samples composed of 100% crosslinked PIL alone showed an average area reduction value of ~53% when the temperature was raised from 20 °C to 70 °C, ~24% when immersed in 1% w/w NaF salt solution and no observable photo-response. In comparison, sIPNs containing 300% w/w linear polymer showed an average area reduction of ~45% when the temperature was raised from 20 °C to 70 °C, ~36% when immersed in 1% NaF w/w salt solution and ~10% after 30 min exposure to white light irradiation, respectively. Moreover, by varying the content of the linear component, fine-control over the photo-, thermo- and salt response, swelling-deswelling rate and mechanical properties of the resulting sIPN was achieved. PMID:26861339

Multicompartmental Microcapsules with Orthogonal Programmable Two-Way Sequencing of Hydrophobic and Hydrophilic Cargo Release.

PubMed

Xu, Weinan; Ledin, Petr A; Iatridi, Zacharoula; Tsitsilianis, Constantinos; Tsukruk, Vladimir V

2016-04-11

Multicompartmental responsive microstructures with the capability for the pre-programmed sequential release of multiple target molecules of opposite solubility (hydrophobic and hydrophilic) in a controlled manner have been fabricated. Star block copolymers with dual-responsive blocks (temperature for poly(N-isopropylacrylamide) chains and pH for poly(acrylic acid) and poly(2-vinylpyridine) arms) and unimolecular micellar structures serve as nanocarriers for hydrophobic molecules in the microcapsule shell. The interior of the microcapsule can be loaded with water-soluble hydrophilic macromolecules. For these dual-loaded microcapsules, a programmable and sequential release of hydrophobic and hydrophilic molecules from the shell and core, respectively, can be triggered independently by temperature and pH variations. These stimuli affect the hydrophobicity and chain conformation of the star block copolymers to initiate out-of-shell release (elevated temperature), or change the overall star conformation and interlayer interactions to trigger increased permeability of the shell and out-of-core release (pH). Reversing stimulus order completely alters the release process. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Phospholipid—polymer amphiphile hybrid assemblies and their interaction with macrophages

PubMed Central

Panneerselvam, Karthiga; Lynge, Martin E.; Riber, Camilla Frich; Mena-Hernando, Sofia; Smith, Anton A. A.; Goldie, Kenneth N.; Zelikin, Alexander N.; Städler, Brigitte

2015-01-01

Recently, the combination of lipids and block copolymers has become an alternative to liposomes and polymersomes as nano-sized drug carriers. We synthesize novel block copolymers consisting of poly(cholesteryl acrylate) as the hydrophobic core and poly(N-isopropylacrylamide) (PNIPAAm) as the hydrophilic extensions. Their successful phospholipid-assisted assembly into vesicles is demonstrated using the evaporation-hydration method. The preserved thermo-responsive property of the lipid-polymer hybrids is shown by a temperature dependent adsorption behaviour of the vesicles to poly(l lysine) coated surfaces. As expected, the vesicle adsorption is found to be higher at elevated temperatures. The cellular uptake efficiency of hybrids is assessed using macrophages with applied shear stress. The amount of adhering macrophages is affected by the time and level of applied shear stress. Further, it is found that shorter PNIPAAm extensions lead to higher uptake of the assemblies by the macrophages with applied shear stress. No inherent cytotoxicity is observed at the tested conditions. Taken together, this first example of responsive lipid-polymer hybrids, and their positive biological evaluation makes them promising nano-sized drug carrier candidates. PMID:26339330

The use of radiation-induced graft polymerization for modification of polymer track membranes

NASA Astrophysics Data System (ADS)

Shtanko, N. I.; Kabanov, V. Ya.; Apel, P. Yu.; Yoshida, M.

1999-05-01

Track membranes (TM) made of poly(ethylene terephtalate) (PET) and polypropylene (PP) films have a number of peculiarities as compared with other ones. They have high mechanical strength at a low thickness, narrow pore size distribution, low content of extractables. However, TM have some disadvantages such as low chemical resistance in alkaline media (PET TM), the low water flow rate due to the hydrophobic nature of their surface. The use of radiation-induced graft polymerization makes it possible to improve the basic characteristics of TM. In this communication our results on the modification of PET and PP TM are presented. The modified membranes were prepared by radiation-induced graft polymerization from the liquid phase. Three methods of grafting were used: (a) the direct method in argon atmosphere; (b) the pre-irradiation of TM in air followed by grafting in argon atmosphere; (c) pre-irradiation in vacuum followed by grafting in vacuum without contacting oxygen. The aim of the work was to investigate some properties of TM modified by grafted poly(methylvinyl pyridine) (PMVP) and poly(N-isopropylacrylamide) (PNIPAAM). It was shown that the modification of TM with hydrophilic polymer results in the growth of the water flow rate. In the past few years many works have been devoted to the synthesis of new polymers - the so-called "intelligent" materials - such as PNIPAAM. However, it is very difficult to make thin membranes of this polymer. Recently, it has been proposed to manufacture composite membranes by grafting stimulus-responsive polymers onto TM. Following this principle, we prepared thermosensitive membranes by the radiation-induced graft polymerization of N-isopropylacrylamide (NIPAAM) onto PET TM. PET TM with the pore size of about 1 μm and pore density of 10 6 cm -2 were first inserted into a solution of NIPAAM containing inhibitor of homopolymerization (CuCl 2) and then exposed to the γ-rays from a 60Co source. The transport properties of the grafted TM were investigated. The permeation of water through the TM was controlled by temperature. The grafted TM exhibited almost the same transition temperature (about 33°C) as that of PNIPAAM.

Responsive polymer-fluorescent carbon nanoparticle hybrid nanogels for optical temperature sensing, near-infrared light-responsive drug release, and tumor cell imaging

NASA Astrophysics Data System (ADS)

Wang, Hui; Ke, Fuyou; Mararenko, Anton; Wei, Zengyan; Banerjee, Probal; Zhou, Shuiqin

2014-06-01

Fluorescent carbon nanoparticles (FCNPs) have been successfully immobilized into poly(N-isopropylacrylamide-co-acrylamide) [poly(NIPAM-AAm)] nanogels based on one-pot precipitation copolymerization of NIPAM monomers with hydrogen bonded FCNP-AAm complex monomers in water. The resultant poly(NIPAM-AAm)-FCNP hybrid nanogels can combine functions from each building block for fluorescent temperature sensing, cell imaging, and near-infrared (NIR) light responsive drug delivery. The FCNPs in the hybrid nanogels not only emit bright and stable photoluminescence (PL) and exhibit up-conversion PL properties, but also increase the loading capacity of the nanogels for curcumin drug molecules. The reversible thermo-responsive swelling/shrinking transition of the poly(NIPAM-AAm) nanogel can not only modify the physicochemical environment of the FCNPs to manipulate the PL intensity for sensing the environmental temperature change, but also regulate the releasing rate of the loaded anticancer drug. In addition, the FCNPs embedded in the nanogels can convert the NIR light to heat, thus an exogenous NIR irradiation can further accelerate the drug release and enhance the therapeutic efficacy. The hybrid nanogels can overcome cellular barriers to enter the intracellular region and light up the mouse melanoma B16F10 cells upon laser excitation. The demonstrated hybrid nanogels with nontoxic and optically active FCNPs immobilized in responsive polymer nanogels are promising for the development of a new generation of multifunctional materials for biomedical applications.Fluorescent carbon nanoparticles (FCNPs) have been successfully immobilized into poly(N-isopropylacrylamide-co-acrylamide) [poly(NIPAM-AAm)] nanogels based on one-pot precipitation copolymerization of NIPAM monomers with hydrogen bonded FCNP-AAm complex monomers in water. The resultant poly(NIPAM-AAm)-FCNP hybrid nanogels can combine functions from each building block for fluorescent temperature sensing, cell imaging, and near-infrared (NIR) light responsive drug delivery. The FCNPs in the hybrid nanogels not only emit bright and stable photoluminescence (PL) and exhibit up-conversion PL properties, but also increase the loading capacity of the nanogels for curcumin drug molecules. The reversible thermo-responsive swelling/shrinking transition of the poly(NIPAM-AAm) nanogel can not only modify the physicochemical environment of the FCNPs to manipulate the PL intensity for sensing the environmental temperature change, but also regulate the releasing rate of the loaded anticancer drug. In addition, the FCNPs embedded in the nanogels can convert the NIR light to heat, thus an exogenous NIR irradiation can further accelerate the drug release and enhance the therapeutic efficacy. The hybrid nanogels can overcome cellular barriers to enter the intracellular region and light up the mouse melanoma B16F10 cells upon laser excitation. The demonstrated hybrid nanogels with nontoxic and optically active FCNPs immobilized in responsive polymer nanogels are promising for the development of a new generation of multifunctional materials for biomedical applications. Electronic supplementary information (ESI) available: Fig. S1-S5. See DOI: 10.1039/c4nr01030b

Injectable nanoengineered stimuli-responsive hydrogels for on-demand and localized therapeutic delivery.

PubMed

Jalili, Nima A; Jaiswal, Manish K; Peak, Charles W; Cross, Lauren M; Gaharwar, Akhilesh K

2017-10-19

"Smart" hydrogels are an emerging class of biomaterials that respond to external stimuli and have been investigated for a range of biomedical applications, including therapeutic delivery and regenerative engineering. Stimuli-responsive nanogels constructed of thermoresponsive polymers such as poly(N-isopropylacrylamide-co-acrylamide) (poly(NIPAM-co-AM)) and magnetic nanoparticles (MNPs) have been developed as "smart carriers" for on-demand delivery of therapeutic biomolecules via magneto-thermal activation. However, due to their small size and systemic introduction, these poly(NIPAM-co-AM)/MNP nanogels result in limited control over long-term, localized therapeutic delivery. Here, we developed an injectable nanoengineered hydrogel loaded with poly(NIPAM-co-AM)/MNPs for localized, on-demand delivery of therapeutics (doxorubicin (DOX)). We have engineered shear-thinning and self-recoverable hydrogels by modulating the crosslinking density of a gelatin methacrylate (GelMA) network. Poly(NIPAM-co-AM)/MNP nanogels loaded with DOX were entrapped within a GelMA pre-polymer solution prior to crosslinking. The temperature and magnetic field dependent release of loaded DOX was observed from the nanoengineered hydrogels (GelMA/(poly(NIPAM-co-AM)/MNPs)). Finally, the in vitro efficacy of DOX released from injectable nanoengineered hydrogels was investigated using preosteoblast and osteosarcoma cells. Overall, these results demonstrated that the injectable nanoengineered hydrogels could be used for on-demand and localized therapeutic delivery for biomedical applications.

Fabrication and characterization of anisotropic nanofiber scaffolds for advanced drug delivery systems

PubMed Central

Jalani, Ghulam; Jung, Chan Woo; Lee, Jae Sang; Lim, Dong Woo

2014-01-01

Stimuli-responsive, polymer-based nanostructures with anisotropic compartments are of great interest as advanced materials because they are capable of switching their shape via environmentally-triggered conformational changes, while maintaining discrete compartments. In this study, a new class of stimuli-responsive, anisotropic nanofiber scaffolds with physically and chemically distinct compartments was prepared via electrohydrodynamic cojetting with side-by-side needle geometry. These nanofibers have a thermally responsive, physically-crosslinked compartment, and a chemically-crosslinked compartment at the nanoscale. The thermally responsive compartment is composed of physically crosslinkable poly(N-isopropylacrylamide) poly(NIPAM) copolymers, and poly(NIPAM-co-stearyl acrylate) poly(NIPAM-co-SA), while the thermally-unresponsive compartment is composed of polyethylene glycol dimethacrylates. The two distinct compartments were physically crosslinked by the hydrophobic interaction of the stearyl chains of poly(NIPAM-co-SA) or chemically stabilized via ultraviolet irradiation, and were swollen in physiologically relevant buffers due to their hydrophilic polymer networks. Bicompartmental nanofibers with the physically-crosslinked network of the poly(NIPAM-co-SA) compartment showed a thermally-triggered shape change due to thermally-induced aggregation of poly(NIPAM-co-SA). Furthermore, when bovine serum albumin and dexamethasone phosphate were separately loaded into each compartment, the bicompartmental nanofibers with anisotropic actuation exhibited decoupled, controlled release profiles of both drugs in response to a temperature. A new class of multicompartmental nanofibers could be useful for advanced nanofiber scaffolds with two or more drugs released with different kinetics in response to environmental stimuli. PMID:24872702

Cell sheet engineering: a unique nanotechnology for scaffold-free tissue reconstruction with clinical applications in regenerative medicine.

PubMed

Elloumi-Hannachi, I; Yamato, M; Okano, T

2010-01-01

Cell sheet technology (CST) is based on the use of thermoresponsive polymers, poly(N-isopropylacrylamide) (PIPAAm). The surface of PIPAAms is formulated in such a way as to make its typical thickness <100 nm. In this review, we first focus on how the methods of PIPAAm-grafted surface preparations and functionalization are important to be able to harvest a functional cell sheet, to be further transplanted. Then, we present aspects of tissue mimics and three-dimensional reconstruction of a tissue in vitro. Finally, we give an overview of clinical applications and clinically relevant animal experimentations of the technology, such as cardiomyopathy, visual acuity, periodonty, oesophageal ulcerations and type 1 diabetes.

Preparation and mechanical characterization of a PNIPA hydrogel composite.

PubMed

Liu, Kaifeng; Ovaert, Timothy C; Mason, James J

2008-04-01

A poly (N-isopropylacrylamide) (PNIPA) hydrogel was synthesized by free radical polymerization and reinforced with a polyurethane foam to make a hydrogel composite. The temperature dependence of the elastic modulus of the PNIPA hydrogel and the composite due to volume phase transition was found using a uniaxial compression test, and the swelling property was investigated using an equilibrium swelling ratio experiment. The gel composite preserves the ability to undergo the volume phase transition and its elastic modulus has strong temperature dependence. The temperature dependence of the elastic modulus and swelling ratio of the gel composite were compared to the PNIPA hydrogel. Not surprisingly, the modulus and swelling ratio of the composite were less dramatic than in the gel.

Injectable gentamicin-loaded thermo-responsive hyaluronic acid derivative prevents infection in a rabbit model.

PubMed

Ter Boo, Gert-Jan A; Arens, Daniel; Metsemakers, Willem-Jan; Zeiter, Stephan; Richards, R Geoff; Grijpma, Dirk W; Eglin, David; Moriarty, T Fintan

2016-10-01

Despite the use of systemic antibiotic prophylaxis, the surgical fixation of open fractures with osteosynthesis implants is associated with high infection rates. Antibiotic-loaded biomaterials (ALBs) are increasingly used in implant surgeries across medical specialties to deliver high concentrations of antibiotics to the surgical site and reduce the risk of implant-associated infection. ALBs which are either less or not restricted in terms of spatial distribution and which may be applied throughout complex wounds could offer improved protection against infection in open fracture care. A thermo-responsive hyaluronic acid derivative (hyaluronic acid-poly(N-isopropylacrylamide) (HApN)) was prepared by a direct amidation reaction between the tetrabutyl ammonium (TBA) salt of hyaluronic acid and amine-terminated poly(N-isopropylacrylamide) (pN). The degree of grafting, and gelation properties of this gel were characterized, and the composition was loaded with gentamicin. The rheological- and release properties of this gentamicin-loaded HApN composition were tested in vitro and its efficacy in preventing infection was tested in a rabbit model of osteosynthesis contaminated with Staphylococcus aureus. The gentamicin-loaded HApN composition was able to prevent bacterial colonization of the implant site as shown by quantitative bacteriology. This finding was supported by histopathological evaluation of the humeri samples where no bacteria were found in the stained sections. In conclusion, this gentamicin-loaded HApN hydrogel effectively prevents infection in a complex wound, simulating a contaminated fracture treated with plating osteosynthesis. Fracture fixation after trauma is associated with high infection rates. Antibiotic loaded biomaterials (ALBs) can provide high local concentrations without systemic side effects. However, the currently available ALBs have limited accessibility to contaminated tissues in open fractures because of predetermined shape. Thus, a novel thermo-responsive hyaluronan based hydrogel with control over gelation temperature is reported. The efficacy of this gentamicin loaded hyaluronan derivative is demonstrated in an in vivo fracture model in the presence of fracture fixation hardware. The bacterial burden is cleared in all of the inoculated rabbits in the presence of the ALB. Thus, the proposed injectable thermo-responsive hyaluronan presents an effective ALB for the prevention of infection. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Smart stimuli sensitive nanogels in cancer drug delivery and imaging: a review.

PubMed

Maya, S; Sarmento, Bruno; Nair, Amrita; Rejinold, N Sanoj; Nair, Shantikumar V; Jayakumar, R

2013-01-01

Nanogels are nanosized hydrogel particles formed by physical or chemical cross-linked polymer networks. The advantageous properties of nanogels related to the ability of retaining considerable amount of water, the biocompatibility of the polymers used, the ability to encapsulate and protect a large quantity of payload drugs within the nanogel matrix, the high stability in aqueous media, their stimuli responsively behavior potential, and the versatility in release drugs in a controlled manner make them very attractive for use in the area of drug delivery. The materials used for the preparation of nanogels ranged from natural polymers like ovalbumin, pullulan, hyaluronic acid, methacrylated chondroitin sulfate and chitosan, to synthetic polymers like poly (N-isopropylacrylamide), poly (Nisopropylacrylamide- co-acrylic acid) and poly (ethylene glycol)-b-poly (methacrylic acid). The porous nanogels have been finding application as anti-cancer drug and imaging agent reservoirs. Smart nanogels responding to external stimuli such as temperature, pH etc can be designed for diverse therapeutic and diagnostic applications. The nanogels have also been surface functionalized with specific ligands aiding in targeted drug delivery. This review focus on stimuli-sensitive, multi-responsive, magnetic and targeted nanogels providing a brief insight on the application of nanogels in cancer drug delivery and imaging in detail.

Functional and surface-active membranes from poly(vinylidene fluoride)-graft-poly(acrylic acid) prepared via RAFT-mediated graft copolymerization.

PubMed

Ying, L; Yu, W H; Kang, E T; Neoh, K G

2004-07-06

Poly (vinylidene fluoride) (PVDF) with "living" poly (acrylic acid) (PAAc) side chains (PVDF-g-PAAc) was prepared by reversible addition-fragmentation chain transfer (RAFT)-mediated graft copolymerization of acrylic acid (AAc) with the ozone-pretreated PVDF. The chemical composition and structure of the copolymers were characterized by elemental analysis, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The copolymer could be readily cast into pH-sensitive microfiltration (MF) membranes with enriched living PAAc graft chains on the surface (including the pore surfaces) by phase inversion in an aqueous medium. The surface composition of the membranes was determined by X-ray photoelectron spectroscopy. The morphology of the membranes was characterized by scanning electron microscopy. The pore size distribution of the membranes was found to be much more uniform than that of the corresponding membranes cast from PVDF-g-PAAc prepared by the "conventional" free-radical graft copolymerization process. Most important of all, the MF membranes with surface-tethered PAAc macro chain transfer agents, or the living membrane surfaces, could be further functionalized via surface-initiated block copolymerization with N-isopropylacrylamide (NIPAAM) to obtain the PVDF-g-PAAc-b-PNIPAAM MF membranes, which exhibited both pH- and temperature-dependent permeability to aqueous media.

The study of N-isopropylacrylamide gel dosimeter doped iodinated contrast agents

NASA Astrophysics Data System (ADS)

Chang, Y. J.; Hsieh, L. L.; Liu, M. H.; Liu, J. S.; Hsieh, B. T.

2013-06-01

Low toxicity of N-isopropylacrylamide (NIPAM) dosimeter was doped with clinical iodinated contrast medium agents(Iobitridol (Xenetix® 350) and organically bound iodine (Conray® 60) as radiation sensitizers; The suitable gel dosimeter preparation formula in this research was 5 w/w% gelatin, 5 w/w% N-isopropylacrylamide, 3 w/w% N,N-methylene-bis-acrylamide, and 5 mM Tetrakis phosphonium chloride. The spiral CT was irradiator, and 120 kVp was the operating tube voltage. The maximum radiation dose was 0.6 Gy, and optical CT was the gel measurement device used. The results showed SERs with the addition of radiosensitizers were 10.70 (Xenetix® 350) and 9.67 (Conray® 60), respectively. Thus, the polymerized gel dosimeter could be used in the efficacy evaluation of low-energy and low-radiation dose.

Synthesis of Thermogelling Poly(N-isopropylacrylamide)-graft-chondroitin Sulfate Composites with Alginate Microparticles for Tissue Engineering

PubMed Central

Christiani, Thomas R.; Toomer, Katelynn; Sheehan, Joseph; Nitzl, Angelika; Branda, Amanda; England, Elizabeth; Graney, Pamela; Iftode, Cristina; Vernengo, Andrea J.

2016-01-01

Injectable biomaterials are defined as implantable materials that can be introduced into the body as a liquid and solidify in situ. Such materials offer the clinical advantages of being implanted minimally invasively and easily forming space-filling solids in irregularly shaped defects. Injectable biomaterials have been widely investigated as scaffolds for tissue engineering. However, for the repair of certain load-bearing areas in the body, such as the intervertebral disc, scaffolds should possess adhesive properties. This will minimize the risk of dislocation during motion and ensure intimate contact with the surrounding tissue, providing adequate transmission of forces. Here, we describe the preparation and characterization of a scaffold composed of thermally sensitive poly(N-isopropylacrylamide)-graft-chondroitin sulfate (PNIPAAM-g-CS) and alginate microparticles. The PNIPAAm-g-CS copolymer forms a viscous solution in water at RT, into which alginate particles are suspended to enhance adhesion. Above the lower critical solution temperature (LCST), around 30 °C, the copolymer forms a solid gel around the microparticles. We have adapted standard biomaterials characterization procedures to take into account the reversible phase transition of PNIPAAm-g-CS. Results indicate that the incorporation of 50 or 75 mg/ml alginate particles into 5% (w/v) PNIPAAm-g-CS solutions quadruple the adhesive tensile strength of PNIPAAm-gCS alone (p<0.05). The incorporation of alginate microparticles also significantly increases swelling capacity of PNIPAAm-g-CS (p<0.05), helping to maintain a space-filling gel within tissue defects. Finally, results of the in vitro toxicology assay kit, 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) and Live/Dead viability assay indicate that the adhesive is capable of supporting the survival and proliferation of encapsulated Human Embryonic Kidney (HEK) 293 cells over 5 days. PMID:27805604

Accelerated cell-sheet recovery from a surface successively grafted with polyacrylamide and poly(N-isopropylacrylamide).

PubMed

Akiyama, Yoshikatsu; Kikuchi, Akihiko; Yamato, Masayuki; Okano, Teruo

2014-08-01

A double polymeric nanolayer consisting of poly(N-isopropylacrylamide) (PIPAAm) and hydrophilic polyacrylamide (PAAm) was deposited on tissue culture polystyrene (TCPS) surfaces using electron beam irradiation to form a new temperature-responsive cell culture surface in which the basal hydrophilic PAAm component in the double polymeric layer promotes the hydration of the upper PIPAAm layer and induces rapid cell detachment compared to a conventional temperature-responsive cell culture surface, PIPAAm-grafted TCPS (PIPAAm-TCPS). Take-off angle-dependent X-ray photoelectron spectroscopy spectral analysis demonstrated that the grafted PIPAAm and PAAm components were located in the upper and basal regions of the double polymeric layer, respectively, suggesting that the double polymeric layer forms an inter-penetrating-network-like structure with PAAm at the basal portion of the PIPAAm grafted chains. The wettability of the temperature-responsive cell culture surfaces with the double polymeric layer tended to be more hydrophilic, with an increase in the basal PAAm graft density at a constant PIPAAm graft density. However, when the graft densities of the upper PIPAAm and basal PAAm were optimized, the resulting temperature-responsive cell culture surface with the double polymeric layer exhibited rapid cell detachment while maintaining cell adhesive character comparable to that of PIPAAm-TCPS. The cell adhesive character was altered from cell-adhesive to cell-repellent with increasing PAAm or PIPAAm graft density. The cell adhesive character of the temperature-responsive cell culture surfaces was relatively consistent with their contact angles. These results strongly suggest that the basal PAAm surface properties affect the degree of hydration and dehydration of the subsequently grafted PIPAAm. In addition, the roles of the hydrophilic component in accelerating cell detachment are further discussed in terms of the mobility of the grafted PIPAAm chains. Applications of this insight might be useful for designing temperature-responsive cell culture surfaces for achieving efficient cell culture and quick target cell detachment. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Facile Fabrication of Hierarchically Thermoresponsive Binary Polymer Pattern for Controlled Cell Adhesion.

PubMed

Hou, Jianwen; Cui, Lele; Chen, Runhai; Xu, Xiaodong; Chen, Jiayue; Yin, Ligang; Liu, Jingchuan; Shi, Qiang; Yin, Jinghua

2018-03-01

A versatile platform allowing capture and detection of normal and dysfunctional cells on the same patterned surface is important for accessing the cellular mechanism, developing diagnostic assays, and implementing therapy. Here, an original and effective method for fabricating binary polymer brushes pattern is developed for controlled cell adhesion. The binary polymer brushes pattern, composed of poly(N-isopropylacrylamide) (PNIPAAm) and poly[poly(ethylene glycol) methyl ether methacrylate] (POEGMA) chains, is simply obtained via a combination of surface-initiated photopolymerization and surface-activated free radical polymerization. This method is unique in that it does not utilize any protecting groups or procedures of backfilling with immobilized initiator. It is demonstrated that the precise and well-defined binary polymer patterns with high resolution are fabricated using this facile method. PNIPAAm chains capture and release cells by thermoresponsiveness, while POEGMA chains possess high capability to capture dysfunctional cells specifically, inducing a switch of normal red blood cells (RBCs) arrays to hemolytic RBCs arrays on the pattern with temperature. This novel platform composed of binary polymer brush pattern is smart and versatile, which opens up pathways to potential applications as microsensors, biochips, and bioassays. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Patterning methods for polymers in cell and tissue engineering.

PubMed

Kim, Hong Nam; Kang, Do-Hyun; Kim, Min Sung; Jiao, Alex; Kim, Deok-Ho; Suh, Kahp-Yang

2012-06-01

Polymers provide a versatile platform for mimicking various aspects of physiological extracellular matrix properties such as chemical composition, rigidity, and topography for use in cell and tissue engineering applications. In this review, we provide a brief overview of patterning methods of various polymers with a particular focus on biocompatibility and processability. The materials highlighted here are widely used polymers including thermally curable polydimethyl siloxane, ultraviolet-curable polyurethane acrylate and polyethylene glycol, thermo-sensitive poly(N-isopropylacrylamide) and thermoplastic and conductive polymers. We also discuss how micro- and nanofabricated polymeric substrates of tunable elastic modulus can be used to engineer cell and tissue structure and function. Such synergistic effect of topography and rigidity of polymers may be able to contribute to constructing more physiologically relevant microenvironment.

Assessment of polyaniline nanoparticles toxicity and teratogenicity in aquatic environment using Rhinella arenarum model.

PubMed

Ibarra, Luis E; Tarres, Lucrecia; Bongiovanni, Silvestre; Barbero, César A; Kogan, Marcelo J; Rivarola, Viviana A; Bertuzzi, Mabel L; Yslas, Edith I

2015-04-01

With the rapid growth of nanotechnology and the applications of nanoparticles, environmental exposure to these particles is increasing. However, their impact in human and environmental health is not well studied. Anurans, with life stage comprising embryos, tadpoles and adults, have an extremely permeable skin which makes them excellent indicators of environmental health. This study evaluated the acute toxicity effects of polyaniline nanoparticles (PANI-Np) in different dispersant on embryos and larvae of Rhinella arenarum. The results showed that LC50 of PANI-Np dispersed in polyvinylpyrrolidone (PVP) were 1,500 mg/L, while LC50 by PANI-Np dispersed in PVP+PNIPAM (polyN-isopropylacrilamide) showed a highest toxicity (1,170 mg/L). The embryo teratogenicity increased with increasing exposure concentration in both kinds of PANI-Np although in PANI-Np1, there is an increased teratogenic effect associated with the polymer stabilizer PVP. Copyright © 2015 Elsevier Inc. All rights reserved.

A thermodynamically-consistent large deformation theory coupling photochemical reaction and electrochemistry for light-responsive gels

NASA Astrophysics Data System (ADS)

Dehghany, Mohammad; Zhang, Haohui; Naghdabadi, Reza; Hu, Yuhang

2018-07-01

Gels are composed of crosslinked polymer network and solvent molecules. When the main chain network is incorporated with functional groups that can undergo photo-chemical reaction upon light irradiation, the gel becomes light-responsive. Under irradiation, the photosensitive groups may undergo photo-ionization process and generate charges that are attached to the main chain or diffuse into the solvent. The newly generated ions disturb the osmotic balance of the gel medium. As a result, water molecules and mobile ions are driven into or out of the network to compensate the osmotic imbalance, which eventually leads to macroscopic swelling or shrinking of the gel. In this work, we develop a rigorous nonequilibrium thermodynamic framework to study the coupled photo-chemo-electro-mechanical responses of the photo-ionizable gels. We first discuss the mathematical descriptions of the light propagation and photo-induced chemical reactions inside the gel, as well as the equations governing the kinetics of the photo-chemical reactions. We then explore the consequences of the fundamental laws of thermodynamics in deriving the governing equations of the photo-ionizable gels. The continuous light irradiation drives the gel system towards a new thermodynamic stationary state that is away from equilibrium and is accompanied by energy dissipation. Next, we focus on the photo stationary state of the gel and explore the consequences of the continuous irradiation on the mechanical response of the gel in both optically thin and optically thick configurations. In the optically thin cases, we quantitatively compare the theoretical prediction with experimental data available in the literature. In one example, we show that the model can quantitatively capture the photo-tunable volume-phase transition of the Poly(N-isopropylacrylamide) (PNIPAM) gel grafted with photo-responsive triphenylmethane leucocyanide groups. In another example, we show that the model can quantitatively study the effect of salt concentration and pH value of the external solution on the photo-induced swelling of the polyacrylamide gels incorporated with triphenylmethane leucohydroxide groups. Finally, for the optically thick gels, we develop a finite element code to study their inhomogeneous deformations due to the light attenuation. This work will be of great importance for precise control and optimal design of photo-ionizable gels in future applications.

Temperature and anion responsive self-assembly of ionic liquid block copolymers coating gold nanoparticles

NASA Astrophysics Data System (ADS)

Li, Junbo; Zhao, Jianlong; Wu, Wenlan; Liang, Ju; Guo, Jinwu; Zhou, Huiyun; Liang, Lijuan

2016-06-01

In this paper, double hydrophilic ionic liquid block copolymers (ILBCs), poly poly[1-methyl-3-(2-methacryloyloxy propylimidazolium bromine)]- block-(N-isopropylacrylamide) (PMMPImB- b-PNIPAAm) was first synthesized by reversible additionfragmentation chain transfer (RAFT) and then attached on the surface of gold nanoparticles (Au NPs) via a strong gold-sulfur bonding for preparing hybrid nanoparticles (PMMPImB- b-PNIPAAm-@-Au NPs). The hybrid NPs had a three layers micelle-like structure, including a gold core, thermo-responsive inner shell and anion responsive outer corona. The self-assembling behavior of thermal- and anion-response from shell and corona were respectively investigated by change of temperature and addition of (CF3SO2)2N-. The results showed the hybrid NPs retained a stable dispersion beyond the lower critical solution temperature (LCST) because of the space or electrostatic protecting by outer PMMPImB. However, with increasing concentration of (CF3SO2)2N-, the micellization of self-assembling PMMPImB- b-PNIPAAm-@-Au NPs was induced to form micellar structure containing the core with hydrophobic PMMPImB-(CF3SO2)2N- surrounded by composite shell of Au NPs-PNIPAAm via the anionresponsive properties of ILBCs. These results indicated that the block copolymers protected plasmonic nanoparticles remain self-assembling properties of block copolymers when phase transition from outer corona polymer.

Patterning Methods for Polymers in Cell and Tissue Engineering

PubMed Central

Kim, Hong Nam; Kang, Do-Hyun; Kim, Min Sung; Jiao, Alex; Kim, Deok-Ho; Suh, Kahp-Yang

2017-01-01

Polymers provide a versatile platform for mimicking various aspects of physiological extracellular matrix properties such as chemical composition, rigidity, and topography for use in cell and tissue engineering applications. In this review, we provide a brief overview of patterning methods of various polymers with a particular focus on biocompatibility and processability. The materials highlighted here are widely used polymers including thermally curable polydimethyl siloxane, ultraviolet-curable polyurethane acrylate and polyethylene glycol, thermo-sensitive poly(N-isopropylacrylamide) and thermoplastic and conductive polymers. We also discuss how micro- and nanofabricated polymeric substrates of tunable elastic modulus can be used to engineer cell and tissue structure and function. Such synergistic effect of topography and rigidity of polymers may be able to contribute to constructing more physiologically relevant microenvironment. PMID:22258887

Fast IR laser mapping ellipsometry for the study of functional organic thin films.

PubMed

Furchner, Andreas; Sun, Guoguang; Ketelsen, Helge; Rappich, Jörg; Hinrichs, Karsten

2015-03-21

Fast infrared mapping with sub-millimeter lateral resolution as well as time-resolved infrared studies of kinetic processes of functional organic thin films require a new generation of infrared ellipsometers. We present a novel laboratory-based infrared (IR) laser mapping ellipsometer, in which a laser is coupled to a variable-angle rotating analyzer ellipsometer. Compared to conventional Fourier-transform infrared (FT-IR) ellipsometers, the IR laser ellipsometer provides ten- to hundredfold shorter measurement times down to 80 ms per measured spot, as well as about tenfold increased lateral resolution of 120 μm, thus enabling mapping of small sample areas with thin-film sensitivity. The ellipsometer, equipped with a HeNe laser emitting at about 2949 cm(-1), was applied for the optical characterization of inhomogeneous poly(3-hexylthiophene) [P3HT] and poly(N-isopropylacrylamide) [PNIPAAm] organic thin films used for opto-electronics and bioapplications. With the constant development of tunable IR laser sources, laser-based infrared ellipsometry is a promising technique for fast in-depth mapping characterization of thin films and blends.

Stimuli-enabled zipper-like graphene interface for auto-switchable bioelectronics.

PubMed

Mishra, Sachin; Ashaduzzaman, Md; Mishra, Prashant; Swart, Hendrik C; Turner, Anthony P F; Tiwari, Ashutosh

2017-03-15

Graphene interfaces with multi-stimuli responsiveness are of particular interest due to their diverse super-thin interfacial behaviour, which could be well suited to operating complex physiological systems in a single miniaturised domain. In general, smart graphene interfaces switch bioelectrodes from the hydrophobic to hydrophilic state, or vice versa, upon triggering. In the present work, a stimuli encoded zipper-like graphene oxide (GrO)/polymer interface was fabricated with in situ poly(N-isopropylacrylamide-co-diethylaminoethylmethylacrylate), i.e., poly(NIPAAm-co-DEAEMA) directed hierarchical self-assembly of GrO and glucose oxidase (GOx). The designed interface exhibited reversible on/off-switching of bio-electrocatalysis on changing the pH between 5 and 8, via phase transition from super hydrophilic to hydrophobic. The study further indicated that the zipper-like interfacial bioelectrochemical properties could be tuned over a modest change of temperature (i.e., 20-40°C). The resulting auto-switchable interface has implications for the design of novel on/off-switchable biodevices with 'in-built' self-control. Copyright © 2016 Elsevier B.V. All rights reserved.

Characterization of stable, electroactive protein cage/synthetic polymer multilayer thin films prepared by layer-by-layer assembly

NASA Astrophysics Data System (ADS)

Uto, Koichiro; Yamamoto, Kazuya; Kishimoto, Naoko; Muraoka, Masahiro; Aoyagi, Takao; Yamashita, Ichiro

2013-04-01

We have fabricated electroactive multilayer thin films containing ferritin protein cages. The multilayer thin films were prepared on a solid substrate by the alternate electrostatic adsorption of (apo)ferritin and poly( N-isopropylacrylamide- co-2-carboxyisopropylacrylamide) (NIPAAm- co-CIPAAm) in pH 3.5 acetate buffer solution. The assembly process was monitored using a quartz crystal microbalance. The (apo)ferritin/poly(NIPAAm- co-CIPAAm) multilayer thin films were then cross-linked using a water-soluble carbodiimide, 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide. The cross-linked films were stable under a variety of conditions. The surface morphology and thickness of the multilayer thin films were characterized by atomic force microscopy, and the ferritin iron cores were observed by scanning electron microscopy to confirm the assembly mechanism. Cyclic voltammetry measurements showed different electrochemical properties for the cross-linked ferritin and apoferritin multilayer thin films, and the effect of stability of the multilayer film on its electrochemical properties was also examined. Our method for constructing multilayer films containing protein cages is expected to be useful in building more complex functional inorganic nanostructures.

Spatiotemporal control of synergistic gel disintegration consisting of boroxole- and glyco-based polymers via photoinduced proton transfer.

PubMed

Kotsuchibashi, Yohei; Ebara, Mitsuhiro; Sato, Takeshi; Wang, Yinan; Rajender, Rajender; Hall, Dennis G; Narain, Ravin; Aoyagi, Takao

2015-02-12

We demonstrate here a local- and remote-control of gel disintegration by using photoinduced proton transfer chemistry of photoacid generator (PAG). The gels were prepared by simply mixing two polymers, poly(N-isopropylacrylamide-co-5-methacrylamido-1,2-benzoxaborole) (P(NIPAAm-co-MAAmBO)) and poly(3-gluconamidopropyl methacrylamide) (PGAPMA) via the synergistic interaction of benzoxaborole and diol groups. The o-nitrobenzaldehyde (o-NBA) was then loaded into the gel as a PAG. The benzoxaborole-diol interaction was successfully disintegrated upon UV irradiation due to the local pH decrease inside the gel. When the gel was irradiated to a specific gel region, the synergistic interactions were disintegrated only at the exposed region. Of special interest is that the whole material eventually transitioned from gel to sol state, as the generated protons diffused gradually toward the nonilluminated region. The ability of the proposed gel-sol transition system via photoinduced proton diffusion may be beneficial for not only prompt pH changes within the gel but also the design of predictive and programmable devices for drug delivery.

Alternating Magnetic Field Controlled, Multifunctional Nano-Reservoirs: Intracellular Uptake and Improved Biocompatibility

NASA Astrophysics Data System (ADS)

Ghosh, Santaneel; Ghoshmitra, Somesree; Cai, Tong; Diercks, David R.; Mills, Nathaniel C.; Hynds, Dianna L.

2010-01-01

Biocompatible magnetic nanoparticles hold great therapeutic potential, but conventional particles can be toxic. Here, we report the synthesis and alternating magnetic field dependent actuation of a remotely controllable, multifunctional nano-scale system and its marked biocompatibility with mammalian cells. Monodisperse, magnetic nanospheres based on thermo-sensitive polymer network poly(ethylene glycol) ethyl ether methacrylate- co-poly(ethylene glycol) methyl ether methacrylate were synthesized using free radical polymerization. Synthesized nanospheres have oscillating magnetic field induced thermo-reversible behavior; exhibiting desirable characteristics comparable to the widely used poly- N-isopropylacrylamide-based systems in shrinkage plus a broader volumetric transition range. Remote heating and model drug release were characterized for different field strengths. Nanospheres containing nanoparticles up to an iron concentration of 6 mM were readily taken up by neuron-like PC12 pheochromocytoma cells and had reduced toxicity compared to other surface modified magnetic nanocarriers. Furthermore, nanosphere exposure did not inhibit the extension of cellular processes (neurite outgrowth) even at high iron concentrations (6 mM), indicating minimal negative effects in cellular systems. Excellent intracellular uptake and enhanced biocompatibility coupled with the lack of deleterious effects on neurite outgrowth and prior Food and Drug Administration (FDA) approval of PEG-based carriers suggest increased therapeutic potential of this system for manipulating axon regeneration following nervous system injury.

PNIPAAm-based biohybrid injectable hydrogel for cardiac tissue engineering.

PubMed

Navaei, Ali; Truong, Danh; Heffernan, John; Cutts, Josh; Brafman, David; Sirianni, Rachael W; Vernon, Brent; Nikkhah, Mehdi

2016-03-01

Injectable biomaterials offer a non-invasive approach to deliver cells into the myocardial infarct region to maintain a high level of cell retention and viability and initiate the regeneration process. However, previously developed injectable matrices often suffer from low bioactivity or poor mechanical properties. To address this need, we introduced a biohybrid temperature-responsive poly(N-isopropylacrylamide) PNIPAAm-Gelatin-based injectable hydrogel with excellent bioactivity as well as mechanical robustness for cardiac tissue engineering. A unique feature of our work was that we performed extensive in vitro biological analyses to assess the functionalities of cardiomyocytes (CMs) alone and in co-culture with cardiac fibroblasts (CFs) (2:1 ratio) within the hydrogel matrix. The synthesized hydrogel exhibited viscoelastic behavior (storage modulus: 1260 Pa) and necessary water content (75%) to properly accommodate the cardiac cells. The encapsulated cells demonstrated a high level of cell survival (90% for co-culture condition, day 7) and spreading throughout the hydrogel matrix in both culture conditions. A dense network of stained F-actin fibers (∼ 6 × 10(4) μm(2) area coverage, co-culture condition) illustrated the formation of an intact and three dimensional (3D) cell-embedded matrix. Furthermore, immunostaining and gene expression analyses revealed mature phenotypic characteristics of cardiac cells. Notably, the co-culture group exhibited superior structural organization and cell-cell coupling, as well as beating behavior (average ∼ 45 beats per min, co-culture condition, day 7). The outcome of this study is envisioned to open a new avenue for extensive in vitro characterization of injectable matrices embedded with 3D mono- and co-culture of cardiac cells prior to in vivo experiments. In this work, we synthesized a new class of biohybrid temperature-responsive poly(N-isopropylacrylamide) PNIPAAm-Gelatin-based injectable hydrogel with suitable bioactivity and mechanical properties for cardiac tissue engineering. A significant aspect of our work was that we performed extensive in vitro biological analyses to assess the functionality of cardiomyocytes alone and in co-culture with cardiac fibroblasts encapsulated within the 3D hydrogel matrix. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

One-pot synthesis of iniferter-bound polystyrene core nanoparticles for the controlled grafting of multilayer shells

NASA Astrophysics Data System (ADS)

Marchyk, Nataliya; Maximilien, Jacqueline; Beyazit, Selim; Haupt, Karsten; Sum Bui, Bernadette Tse

2014-02-01

A novel approach using one-pot synthesis for the production of uniform, iniferter-bound polystyrene core nanoparticles of size 30-40 nm is described. Conventional oil-in-water emulsion polymerisation of styrene and divinylbenzene, combining a hybrid initiation system (thermal and UV), triggered sequentially, was employed to form the surface-bound thiocarbamate iniferters in situ. The iniferter cores were then used as seeds for re-initiating further polymerisation by UV irradiation to produce water-compatible core-shell nanoparticles. Grafting of various shell-types is demonstrated: linear polymers of poly(N-isopropylacrylamide) brushes, crosslinked polymers bearing different surface charges and molecularly imprinted polymers. The shell thickness was readily tuned by varying the monomers' concentration and polymerisation time. Our method is straightforward and in addition, gives access to the preparation of fluorescent seeds and the possibility of grafting nanosized multiple shells. The core-shell nanoparticles were fully characterised by dynamic light scattering, transmission electron microscopy, Fourier transform infrared spectroscopy and microelemental analysis.A novel approach using one-pot synthesis for the production of uniform, iniferter-bound polystyrene core nanoparticles of size 30-40 nm is described. Conventional oil-in-water emulsion polymerisation of styrene and divinylbenzene, combining a hybrid initiation system (thermal and UV), triggered sequentially, was employed to form the surface-bound thiocarbamate iniferters in situ. The iniferter cores were then used as seeds for re-initiating further polymerisation by UV irradiation to produce water-compatible core-shell nanoparticles. Grafting of various shell-types is demonstrated: linear polymers of poly(N-isopropylacrylamide) brushes, crosslinked polymers bearing different surface charges and molecularly imprinted polymers. The shell thickness was readily tuned by varying the monomers' concentration and polymerisation time. Our method is straightforward and in addition, gives access to the preparation of fluorescent seeds and the possibility of grafting nanosized multiple shells. The core-shell nanoparticles were fully characterised by dynamic light scattering, transmission electron microscopy, Fourier transform infrared spectroscopy and microelemental analysis. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr05295h

Synthesis of Poly(N-isopropylacrylamide) Microcapsules for Drug Delivery Applications via UV Aerosol Photopolymerization

NASA Astrophysics Data System (ADS)

Roberson, Nicole; Denmark, Daniel; Witanachchi, Sarath

Hybrid drug delivery systems composed of thermoresponsive polymers and magnetic nanoparticles have been developed using chemical methods to deliver controlled amounts of a biotherapeutic to target tissue. These methods can be expensive, time intensive, and produce impure composites due to the use of surfactants during polymer synthesis. In this study, UV aerosol photopolymerization is used to synthesize N-isoplopylacrylamide (NIPAM) monomers, N,N-methylenebisacrylamide (MBA) crosslinker, and irgacure 2959 photoinitiator into the transporting microcapsule for drug delivery. The method of UV aerosol photopolymerization allows for the continuous, cost effective, and time efficient synthesis of a high concentration of pure polymers in a short amount of time; toxic surfactants are not necessary. Optimal NIPAM monomer, MBA crosslinker, and irgacure 2959 photoinitiator concentrations were tested and analyzed to synthesize a microcapsule with optimal conditions for controlled drug delivery. Scanning Electron Microscope (SEM) imaging reveals that synthesis of polymer microcapsules of about 30 micrometers in size is effective through UV aerosol photopolymerization. Findings will contribute greatly to the field of emergency medicine. This work was supported by the United States Army (Grant No. W81XWH1020101/3349).

Breathable NIPAAm Network with Controllable Hydration Supports Model Lipid Membrane

NASA Astrophysics Data System (ADS)

Jablin, Michael; Smith, Hillary; Zhernenkov, Mikhail; Vidyasagar, Ajay; Toomey, Ryan; Saiz, Jessica; Toperverg, Boris; Watkins, Erik; Kuhl, Tonya; Hurd, Alan; Majewski, Jaroslaw

2009-03-01

The interaction of a model lipid bilayer composed of DPPC with a surface-tethered poly(N-isopropylacrylamide) (NIPAAm) was explored with neutron reflectometry (NR). The Langmuir-Blodgett / Langmuir-Schaeffer method was used to deposit a lipid bilayer onto the polymer. NR measurements were used to probe the in- and out-of-plane structure of the system as a function of temperature. NR with fluorescence microscopy show that the polymer supports a lipid bilayer, and hydration of the support can be controlled. At low temp. the membrane develops out-of-plane undulations visible in off-specular scattering. Analysis of the off-specular reveals in-plane correlation of the bilayer fluctuations. The separation of the lipid bilayer from the solid support of a substrate constitutes a significant step towards a more realistic model of biological membranes.

Serum-Stable, Long-Circulating, pH-Sensitive PEGylated Liposomes.

PubMed

Bertrand, Nicolas; Simard, Pierre; Leroux, Jean-Christophe

2017-01-01

pH-sensitive liposomes have been designed to deliver active compounds, specifically to acidic intracellular organelles, and to augment their cytoplasmic concentrations. These systems combine the protective effects of other liposomal formulations with specific environment-controlled drug release. They are stable at physiological pH, but abruptly discharge their contents when endocytosed into acidic compartments, allowing the drug to be released before it is exposed to the harsh environment of the lysosomes.Serum-stable formulations with minimal leakage at physiological pH and rapid drug release at pH 5.0 to 5.5 can be easily prepared by inserting a hydrophobically modified N-isopropylacrylamide/methacrylic acid copolymer (poly(NIPAM-co-MAA)) in the lipid bilayer of sterically stabilized liposomes. The present chapter describes polymer synthesis, as well as the preparation and characterization of large unilamellar pH-sensitive vesicles.

Thermosensitive block copolymer [(PNIPAM)-b-(Glycine)] thin film as protective layer for drug loaded mesoporous silica nanoparticles

NASA Astrophysics Data System (ADS)

Amgoth, Chander; Joshi, Suman

2017-10-01

Synthesis and characterization of [(PNIPAM)-b-(Gly)] and mesoporous silica nanoparticles (MP-SiO2 NPs) were carried out separately and used to develop [(PNIPAM)-b-(Gly)]-(MP-SiO2 NPs). The synthesized MP-SiO2 NPs were meso porous in nature. The size of SiO2 NPs is in the range of ~180-250 nm (in diameter) with an average pore size of 2.8 nm within the particles. Interestingly, these mesoporous SiO2 NPs were loaded with anticancer drug (ITM-imatinib mesylate) fallow by the incubation for 24 h at RT. However, ITM loaded MP-SiO2 NPs were capped or covered with synthesized [(PNIPAM)-b-(Gly)] thin film. Here, thin film acts as protective layer for drug loaded MP-SiO2 NPs, with that leakage of drug molecules throughout its transport pathway can be avoided. Significantly, thermosensitive [(PNIPAM)-b-(Gly)] polymer thin film depletes at body temperature (~37 °C) and drug molecules come out from the pores of SiO2 NPs. However, developed [(PNIPAM)-b-(Gly)]-(MP-SiO2 NPs) is compatible and used for cell inhibition studies. After 24 h treatment, drug ITM released from [(PNIPAM)-b-(Gly)]-(MP-SiO2 NPs) shows significant (>90%) inhibition on leukemia blood cancer (K562) cells.

Preparation of end-grafted polymer brushes by nitroxide-mediated free radical polymerization of vaporized vinyl monomers.

PubMed

Li, Jun; Chen, Xiaoru; Chang, Ying-Chih

2005-10-11

In this work, we report a gas-phase polymerization approach to create end-grafted vinyl based polymer films on silicon oxide based substrates. The "surface-initiated vapor deposition polymerization" (SI-VDP) of vaporized vinyl monomers, via the nitroxide-mediated free radical polymerization mechanism, was developed to fabricate various homo- and block copolymer brushes from surface-bound initiators, 1-(4'-oxa-2'-phenyl-12'-trimethoxysilyldodecyloxy)-2,2,6,6-tetra-methylpiperidine ("TEMPO"). The resulting polymer thin films were characterized by the Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, ellipsometry, and contact angle goniometry, respectively, to identify the surface composition, film thickness, surface coverage, and water contact angles. Through the SI-VDP, end-grafted polymer films of polystyrene (PSt), poly(acrylic acid) (PAAc), poly(N-(2-hydroxypropyl) methacrylamide) (PHPMA), and poly(N-isopropylacrylamide) (PNIPAAm) with 10-200 nm thicknesses were fabricated. Furthermore, the block copolymer films of PAAc (1st block)-b-PSt (2nd block), PSt (1st block)-b-PAAc (2nd block), and a triblock copolymer film of PAAc (1st)-b-PSt (2nd)-b-PHPMA (3rd), were also fabricated, suggesting the "renewability" of the TEMPO-initiated polymerization in the SI-VDP scheme. It is also noticed that the SI-VDP is more efficient than the conventional solution phase polymerization in producing functional polymer brushes such as PNIPAAm, PAAc, or PAAc-b-PSt end-grafted films. In summary, our studies have shown clear advantages of the SI-VDP setup for the nitroxide-mediated polymerization scheme in controlling synthesis of end-grafted homo- and copolymer thin films.

Synthesis of high generation thermo-sensitive dendrimers for extraction of rivaroxaban from human fluid and pharmaceutic samples.

PubMed

Parham, Negin; Panahi, Homayon Ahmad; Feizbakhsh, Alireza; Moniri, Elham

2018-04-13

In this present study, poly (N-isopropylacrylamide) as a thermo-sensitive agent was grafted onto magnetic nanoparticles, then ethylenediamine and methylmethacrylate were used to synthesize the first generation of poly amidoamine (PAMAM) dendrimers successively and the process continued alternatively until the ten generations of dendrimers. The synthesized nanocomposite was investigated using Fourier transform infrared spectrometry, thermalgravimetry analysis, X-ray diffractometry, elemental analysis and vibrating-sample magnetometer. The particle size and morphology were characterized using dynamic light scattering, field emission scanning electron microscopy and transmission electron microscopy. Batch experiments were conducted to investigate the parameters affecting adsorption and desorption of rivaroxaban by synthesized nanocomposite. The maximum sorption of rivaroxaban by the synthesized nanocomposite was obtained at pH of 8. The resulting grafted magnetic nanoparticle dendrimers were applied for extraction of rivaroxaban from biologic human liquids and medicinal samples. The specifications of rivaroxaban sorbed by a magnetic nanoparticle dendrimer showed good accessibility and high capacity of the active sites within the dendrimers. Urine and drug matrix extraction recoveries of more than 92.5 and 99.8 were obtained, respectively. Copyright © 2018 Elsevier B.V. All rights reserved.

Development of a self-cleaning sensor membrane for implantable biosensors.

PubMed

Gant, Rebecca M; Hou, Yaping; Grunlan, Melissa A; Coté, Gerard L

2009-09-01

Fibrous tissue encapsulation may slow the diffusion of the target analyte to an implanted sensor and compromise the optical signal. Poly(N-isopropylacrylamide) (PNIPAAm) hydrogels are thermoresponsive, exhibiting temperature-modulated swelling behavior that could be used to prevent biofouling. Unfortunately, PNIPAAm hydrogels are limited by poor mechanical strength. In this study, a unique thermoresponsive nanocomposite hydrogel was developed to create a mechanically robust self-cleaning sensor membrane for implantable biosensors. This hydrogel was prepared by the photochemical cure of an aqueous solution of NIPAAm and copoly(dimethylsiloxane/methylvinylsiloxane) colloidal nanoparticles ( approximately 219 nm). At temperatures above the volume phase transition temperature (VPTT) of approximately 33-34 degrees C, the hydrogel deswells and becomes hydrophobic, whereas lowering the temperature below the VPTT causes the hydrogel to swell and become hydrophilic. The potential of this material to minimize biofouling via temperature-modulation while maintaining sensor viability was investigated using glucose as a target analyte. PNIPAAm composite hydrogels with and without poration were compared to a pure PNIPAAm hydrogel and a nonthermoresponsive poly(ethylene glycol) (PEG) hydrogel. Poration led to a substantial increase in diffusion. Cycling the temperature of the nanocomposite hydrogels around the VPTT caused significant detachment of GFP-H2B 3T3 fibroblast cells.

Strategies for the chemical and biological functionalization of scaffolds for cardiac tissue engineering: a review.

PubMed

Tallawi, Marwa; Rosellini, Elisabetta; Barbani, Niccoletta; Cascone, Maria Grazia; Rai, Ranjana; Saint-Pierre, Guillaume; Boccaccini, Aldo R

2015-07-06

The development of biomaterials for cardiac tissue engineering (CTE) is challenging, primarily owing to the requirement of achieving a surface with favourable characteristics that enhances cell attachment and maturation. The biomaterial surface plays a crucial role as it forms the interface between the scaffold (or cardiac patch) and the cells. In the field of CTE, synthetic polymers (polyglycerol sebacate, polyethylene glycol, polyglycolic acid, poly-l-lactide, polyvinyl alcohol, polycaprolactone, polyurethanes and poly(N-isopropylacrylamide)) have been proven to exhibit suitable biodegradable and mechanical properties. Despite the fact that they show the required biocompatible behaviour, most synthetic polymers exhibit poor cell attachment capability. These synthetic polymers are mostly hydrophobic and lack cell recognition sites, limiting their application. Therefore, biofunctionalization of these biomaterials to enhance cell attachment and cell material interaction is being widely investigated. There are numerous approaches for functionalizing a material, which can be classified as mechanical, physical, chemical and biological. In this review, recent studies reported in the literature to functionalize scaffolds in the context of CTE, are discussed. Surface, morphological, chemical and biological modifications are introduced and the results of novel promising strategies and techniques are discussed.

Strategies for the chemical and biological functionalization of scaffolds for cardiac tissue engineering: a review

PubMed Central

Tallawi, Marwa; Rosellini, Elisabetta; Barbani, Niccoletta; Cascone, Maria Grazia; Rai, Ranjana; Saint-Pierre, Guillaume; Boccaccini, Aldo R.

2015-01-01

The development of biomaterials for cardiac tissue engineering (CTE) is challenging, primarily owing to the requirement of achieving a surface with favourable characteristics that enhances cell attachment and maturation. The biomaterial surface plays a crucial role as it forms the interface between the scaffold (or cardiac patch) and the cells. In the field of CTE, synthetic polymers (polyglycerol sebacate, polyethylene glycol, polyglycolic acid, poly-l-lactide, polyvinyl alcohol, polycaprolactone, polyurethanes and poly(N-isopropylacrylamide)) have been proven to exhibit suitable biodegradable and mechanical properties. Despite the fact that they show the required biocompatible behaviour, most synthetic polymers exhibit poor cell attachment capability. These synthetic polymers are mostly hydrophobic and lack cell recognition sites, limiting their application. Therefore, biofunctionalization of these biomaterials to enhance cell attachment and cell material interaction is being widely investigated. There are numerous approaches for functionalizing a material, which can be classified as mechanical, physical, chemical and biological. In this review, recent studies reported in the literature to functionalize scaffolds in the context of CTE, are discussed. Surface, morphological, chemical and biological modifications are introduced and the results of novel promising strategies and techniques are discussed. PMID:26109634

Polymer-Based Protein Engineering: Synthesis and Characterization of Armored, High Graft Density Polymer-Protein Conjugates.

PubMed

Carmali, Sheiliza; Murata, Hironobu; Cummings, Chad; Matyjaszewski, Krzysztof; Russell, Alan J

2017-01-01

Atom transfer radical polymerization (ATRP) from the surface of a protein can generate remarkably dense polymer shells that serve as armor and rationally tune protein function. Using straightforward chemistry, it is possible to covalently couple or display multiple small molecule initiators onto a protein surface. The chemistry is fine-tuned to be sequence specific (if one desires a single targeted site) at controlled density. Once the initiator is anchored on the protein surface, ATRP is used to grow polymers on protein surface, in situ. The technique is so powerful that a single-protein polymer conjugate molecule can contain more than 90% polymer coating by weight. If desired, stimuli-responsive polymers can be "grown" from the initiated sites to prepare enzyme conjugates that respond to external triggers such as temperature or pH, while still maintaining enzyme activity and stability. Herein, we focus mainly on the synthesis of chymotrypsin-polymer conjugates. Control of the number of covalently coupled initiator sites by changing the stoichiometric ratio between enzyme and the initiator during the synthesis of protein-initiator complexes allowed fine-tuning of the grafting density. For example, very high grafting density chymotrypsin conjugates were prepared from protein-initiator complexes to grow the temperature-responsive polymers, poly(N-isopropylacrylamide), and poly[N,N'-dimethyl(methacryloyloxyethyl) ammonium propane sulfonate]. Controlled growth of polymers from protein surfaces enables one to predictably manipulate enzyme kinetics and stability without the need for molecular biology-dependent mutagenesis. © 2017 Elsevier Inc. All rights reserved.

Removal of radioactive contaminants by polymeric microspheres.

PubMed

Osmanlioglu, Ahmet Erdal

2016-11-01

Radionuclide removal from radioactive liquid waste by adsorption on polymeric microspheres is the latest application of polymers in waste management. Polymeric microspheres have significant immobilization capacity for ionic substances. A laboratory study was carried out by using poly(N-isopropylacrylamide) for encapsulation of radionuclide in the liquid radioactive waste. There are numbers of advantages to use an encapsulation technology in radioactive waste management. Results show that polymerization step of radionuclide increases integrity of solidified waste form. Test results showed that adding the appropriate polymer into the liquid waste at an appropriate pH and temperature level, radionuclide was encapsulated into polymer. This technology may provide barriers between hazardous radioactive ions and the environment. By this method, solidification techniques became easier and safer in nuclear waste management. By using polymer microspheres as dust form, contamination risks were decreased in the nuclear industry and radioactive waste operations.

Hydrogels Containing Prussian Blue Nanoparticles Toward Removal of Radioactive Cesium Ions.

PubMed

Kamachi, Yuichiro; Zakaria, Mohamed B; Torad, Nagy L; Nakato, Teruyuki; Ahamad, Tansir; Alshehri, Saad M; Malgras, Victor; Yamauchil, Yusuke

2016-04-01

Recent reports have demonstrated the practical application of Prussian blue (PB) nanoparticles toward environmental clean-up of radionuclide 173Cs. Herein, we prepared a large amount of PB nanoparticles by mixing both iron(III) chloride and sodium ferrocyanide hydrate as starting precursors. The obtained PB nanoparticles show a high surface area (440 m2. g-1) and consequently an excellent uptake ability of Cs ions from aqueous solutions. The uptake ability of Cs ions into poly(N-isopropylacrylamide (PNIPA) hydrogel is drastically increased up to 156.7 m2. g-1 after incorporating our PB nanoparticles, compared to 30.2 m2 . g-1 after using commercially available PB. Thus, our PB-containing PNIPA hydrogel can be considered as an excellent candidate for the removal of Cs ions from aqueous solutions, which will be useful for the remediation of the nuclear waste.

Reversible gating of smart plasmonic molecular traps using thermoresponsive polymers for single-molecule detection

PubMed Central

Zheng, Yuanhui; Soeriyadi, Alexander H.; Rosa, Lorenzo; Ng, Soon Hock; Bach, Udo; Justin Gooding, J.

2015-01-01

Single-molecule surface-enhanced Raman spectroscopy (SERS) has attracted increasing interest for chemical and biochemical sensing. Many conventional substrates have a broad distribution of SERS enhancements, which compromise reproducibility and result in slow response times for single-molecule detection. Here we report a smart plasmonic sensor that can reversibly trap a single molecule at hotspots for rapid single-molecule detection. The sensor was fabricated through electrostatic self-assembly of gold nanoparticles onto a gold/silica-coated silicon substrate, producing a high yield of uniformly distributed hotspots on the surface. The hotspots were isolated with a monolayer of a thermoresponsive polymer (poly(N-isopropylacrylamide)), which act as gates for molecular trapping at the hotspots. The sensor shows not only a good SERS reproducibility but also a capability to repetitively trap and release molecules for single-molecular sensing. The single-molecule sensitivity is experimentally verified using SERS spectral blinking and bianalyte methods. PMID:26549539

Amplification of hofmeister effect by alcohols.

PubMed

Xu, Yun; Liu, Guangming

2014-07-03

We have demonstrated that Hofmeister effect can be amplified by adding alcohols to aqueous solutions. The lower critical solution temperature behavior of poly(N-isopropylacrylamide) has been employed as the model system to study the amplification of Hofmeister effect. The alcohols can more effectively amplify the Hofmeister effect following the series methanol < ethanol < 1-propanol < 2-propanol for the monohydric alcohols and following the series d-sorbitol ≈ xylitol ≈ meso-erythritol < glycerol < ethylene glycol < methanol for the polyhydric alcohols. Our study reveals that the relative extent of amplification of Hofmeister effect is determined by the stability of the water/alcohol complex, which is strongly dependent on the chemical structure of alcohols. The more stable solvent complex formed via stronger hydrogen bonds can more effectively differentiate the anions through the anion-solvent complex interactions, resulting in a stronger amplification of Hofmeister effect. This study provides an alternative method to tune the relative strength of Hofmeister effect besides salt concentration.

A Smart Superwetting Surface with Responsivity in Both Surface Chemistry and Microstructure.

PubMed

Zhang, Dongjie; Cheng, Zhongjun; Kang, Hongjun; Yu, Jianxin; Liu, Yuyan; Jiang, Lei

2018-03-26

Recently, smart surfaces with switchable wettability have aroused much attention. However, only single surface chemistry or the microstructure can be changed on these surfaces, which significantly limits their wetting performances, controllability, and applications. A new surface with both tunable surface microstructure and chemistry was prepared by grafting poly(N-isopropylacrylamide) onto the pillar-structured shape memory polymer on which multiple wetting states from superhydrophilicity to superhydrophobicity can be reversibly and precisely controlled by synergistically regulating the surface microstructure and chemistry. Meanwhile, based on the excellent controllability, we also showed the application of the surface as a rewritable platform, and various gradient wettings can be obtained. This work presents for the first time a surface with controllability in both surface chemistry and microstructure, which starts some new ideas for the design of novel superwetting materials. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Thermo-responsive gels that absorb moisture and ooze water.

PubMed

Matsumoto, Kazuya; Sakikawa, Nobuki; Miyata, Takashi

2018-06-13

The water content of thermo-responsive hydrogels can be drastically altered by small changes in temperature because their polymer chains change from hydrophilic to hydrophobic above their low critical solution temperature (LCST). In general, such smart hydrogels have been utilized in aqueous solutions or in their wet state, and no attempt has been made to determine the phase-transition behavior of the gels in their dried states. Here we demonstrate an application of the thermo-responsive behavior of an interpenetrating polymer network (IPN) gel comprising thermo-responsive poly(N-isopropylacrylamide) and hydrophilic sodium alginate networks in their dried states. The dried IPN gel absorbs considerable moisture from air at temperatures below its LCST and oozes the absorbed moisture as liquid water above its LCST. These phenomena provide energy exchange systems in which moisture from air can be condensed to liquid water using the controllable hydrophilic/hydrophobic properties of thermo-responsive gels with a small temperature change.

Selective adsorption of oppositely charged PNIPAAM on halloysite surfaces: a route to thermo-responsive nanocarriers.

PubMed

Cavallaro, Giuseppe; Lazzara, Giuseppe; Lisuzzo, Lorenzo; Milioto, Stefana; Parisi, Filippo

2018-08-10

Halloysite nanotubes were functionalized with stimuli-responsive macromolecules to generate smart nanohybrids. Poly(N-isopropylacrylamide)-co-methacrylic acid (PNIPAAM-co-MA) was selectively adsorbed into halloysite lumen by exploiting electrostatic interactions. Amine-terminated PNIPAAM polymer was also investigated that selectively interacts with the outer surface of the nanotubes. The adsorption site has a profound effect on the thermodynamic behavior and therefore temperature responsive features of the hybrid material. The drug release kinetics was investigated by using diclofenac as a non-steroidal anti-inflammatory drug model. The release kinetics depends on the nanoarchitecture of the PNIPAAM/halloysite based material. In particular, diclofenac release was slowed down above the LCST for PNIPAAM-co-MA/halloysite. Opposite trends occurred for halloysite functionalized with PNIPAAM at the outer surface. This work represents a further step toward the opportunity to extend and control the delivery conditions of active species, which represent a key point in technological applications.

Biocompatibility and intradiscal application of a thermoreversible celecoxib-loaded poly-N-isopropylacrylamide MgFe-layered double hydroxide hydrogel in a canine model.

PubMed

Willems, Nicole; Yang, Hsiao-Yin; Langelaan, Marloes L P; Tellegen, Anna R; Grinwis, Guy C M; Kranenburg, Hendrik-Jan C; Riemers, Frank M; Plomp, Saskia G M; Craenmehr, Eric G M; Dhert, Wouter J A; Papen-Botterhuis, Nicole E; Meij, Björn P; Creemers, Laura B; Tryfonidou, Marianna A

2015-08-20

Chronic low back pain due to intervertebral disc (IVD) degeneration is associated with increased levels of inflammatory mediators. Current medical treatment consists of oral anti-inflammatory drugs to alleviate pain. In this study, the efficacy and safety of a novel thermoreversible poly-N-isopropylacrylamide MgFe-layered double hydroxide (pNIPAAM MgFe-LDH) hydrogel was evaluated for intradiscal controlled delivery of the selective cyclooxygenase (COX) 2 inhibitor and anti-inflammatory drug celecoxib (CXB). Degradation, release behavior, and the ability of a CXB-loaded pNIPAAM MgFe-LDH hydrogel to suppress prostaglandin E2 (PGE2) levels in a controlled manner in the presence of a proinflammatory stimulus (TNF-α) were evaluated in vitro. Biocompatibility was evaluated histologically after subcutaneous injection in mice. Safety of intradiscal application of the loaded and unloaded hydrogels was studied in a canine model of spontaneous mild IVD degeneration by histological, biomolecular, and biochemical evaluation. After the hydrogel was shown to be biocompatible and safe, an in vivo dose-response study was performed in order to determine safety and efficacy of the pNIPAAM MgFe-LDH hydrogel for intradiscal controlled delivery of CXB. CXB release correlated to hydrogel degradation in vitro. Furthermore, controlled release from CXB-loaded hydrogels was demonstrated to suppress PGE2 levels in the presence of TNF-α. The hydrogel was shown to exhibit a good biocompatibility upon subcutaneous injection in mice. Upon intradiscal injection in a canine model, the hydrogel exhibited excellent biocompatibility based on histological evaluation of the treated IVDs. Gene expression and biochemical analyses supported the finding that no substantial negative effects of the hydrogel were observed. Safety of application was further confirmed by the absence of clinical symptoms, IVD herniation or progression of degeneration. Controlled release of CXB resulted in a nonsignificant maximal inhibition (approximately 35 %) of PGE2 levels in the mildly degenerated canine IVDs. In conclusion, this study showed biocompatibility and safe intradiscal application of an MgFe LDH-pNIPAAM hydrogel. Controlled release of CXB resulted in only limited inhibition of PGE2 in this model with mild IVD degeneration, and further studies should concentrate on application of controlled release from this type of hydrogel in animal models with more severe IVD degeneration.

Metal-organic framework tethering PNIPAM for ON-OFF controlled release in solution.

PubMed

Nagata, Shunjiro; Kokado, Kenta; Sada, Kazuki

2015-05-21

A smart metal-organic framework (MOF) exhibiting controlled release was achieved by modification with a thermoresponsive polymer (PNIPAM) via a surface-selective post-synthetic modification technique. Simple temperature variation readily switches "open" (lower temperature) and "closed" (higher temperature) states of the polymer-modified MOF through conformational change of PNIPAM grafted onto the MOF, resulting in controlled release of the included guest molecules such as resorufin, caffeine, and procainamide.

Facile assembly of 3D binary colloidal crystals from soft microgel spheres.

PubMed

Liu, Yang; Guan, Ying; Zhang, Yongjun

2014-03-01

It still remains a big challenge to fabricate binary colloidal crystals (binary CCs) from hard colloidal spheres, although a lot of efforts have been made. Here, for the first time, binary CCs are assembled from soft hydrogel spheres, PNIPAM microgels, instead of hard spheres. Different from hard spheres, microgel binary CCs can be facilely fabricated by simply heating binary microgel dispersions to 37 °C and then allowing them to cool back to room temperature. The formation of highly ordered structure is indicated by the appearance of an iridescent color and a sharp Bragg diffraction peak. Compared with hard sphere binary CCs, the assembly of PNIPAM microgel binary CCs is much simpler, faster and with a higher "atom" economy. The easy formation of PNIPAM microgel binary CC is attributed to the thermosensitivity and soft nature of the PNIPAM microgel spheres. In addition, PNIPAM microgel binary CCs can respond to temperature change, and their stop band can be tuned by changing the concentration of the dispersion. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Kinetics of temperature response of PEO-b-PNIPAM-b-PAA triblock terpolymer aggregates and of their complexes with lysozyme

DOE PAGES

Papagiannopoulos, Aristeidis; Meristoudi, Anastasia; Hong, Kunlun; ...

2015-12-18

We present the kinetics of temperature response of a PEO-b-PNIPAM-b-PAA triblock terpolymer and of its complexes with lysozyme in aqueous solution. It is found that during the coil-to-globule transition of PNIPAM new bonds within the polymer aggregates are created, making the transition of the aggregates partially irreversible. This effect is also found for the protein loaded PEO-b-PNIPAM-b-PAA aggregates whereas in this case protein globules appear to enhance the formation of bonds, making the transition totally irreversible. The internal dynamics of both aggregates and complexes are “frozen” once the temperature is increased upon PINIPAM's LCST in water and remain so evenmore » when the temperature drops below LCST. As a result, we investigate the complexation kinetics of lysozyme and PEO-b-PNIPAM-b-PAA and observe that it occurs in two stages, one where protein globules adsorb on single pre-formed aggregates and one where protein globules cause inter-aggregate clustering.« less

Kinetics of temperature response of PEO-b-PNIPAM-b-PAA triblock terpolymer aggregates and of their complexes with lysozyme

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

Papagiannopoulos, Aristeidis; Meristoudi, Anastasia; Hong, Kunlun

We present the kinetics of temperature response of a PEO-b-PNIPAM-b-PAA triblock terpolymer and of its complexes with lysozyme in aqueous solution. It is found that during the coil-to-globule transition of PNIPAM new bonds within the polymer aggregates are created, making the transition of the aggregates partially irreversible. This effect is also found for the protein loaded PEO-b-PNIPAM-b-PAA aggregates whereas in this case protein globules appear to enhance the formation of bonds, making the transition totally irreversible. The internal dynamics of both aggregates and complexes are “frozen” once the temperature is increased upon PINIPAM's LCST in water and remain so evenmore » when the temperature drops below LCST. As a result, we investigate the complexation kinetics of lysozyme and PEO-b-PNIPAM-b-PAA and observe that it occurs in two stages, one where protein globules adsorb on single pre-formed aggregates and one where protein globules cause inter-aggregate clustering.« less

Rapid, High Affinity Binding by a Fluorescein Templated Copolymer Combining Covalent, Hydrophobic, and Acid–Base Noncovalent Crosslinks

PubMed Central

Timberman, Anthony; Yang, Rongfang; Papantones, Alex; Seitz, W. Rudolf

2018-01-01

A new type of biomimetic templated copolymer has been prepared by reverse addition fragmentation chain transfer polymerization (RAFT) in dioxane. The initial formulation includes the template fluorescein, N-isopropylacrylamide (NIPAM, 84 mol %), methacrylic acid (MAA, 5-mol %), 4-vinylpyridine (4-VP, 9 mmol %), and N,N′-methylenebis(acrylamide) (MBA, 2 mol %). PolyNIPAM is a thermosensitive polymer that comes out of aqueous solution above its lower critical solution temperature forming hydrophobic ‘crosslinks’. MAA and 4-VP interact in dioxane forming acid–base crosslinks. The excess 4-VP serves as a recognition monomer organizing around the template fluorescein to form a binding site that is held in place by the noncovalent and covalent crosslinks. The MBA is a covalent crosslinker. The RAFT agent in the resulting copolylmer was reduced to a thiol and attached to gold nanoparticles. The gold nanoparticle bound copolymer binds fluorescein completely in less than two seconds with an affinity constant greater than 108 M−1. A reference copolymer prepared with the same monomers by the same procedure binds fluorescein much more weakly. PMID:29693601

Stimuli-responsive magnetic nanomicelles as multifunctional heat and cargo delivery vehicles.

PubMed

Kim, Dong-Hyun; Vitol, Elina A; Liu, Jing; Balasubramanian, Shankar; Gosztola, David J; Cohen, Ezra E; Novosad, Valentyn; Rozhkova, Elena A

2013-06-18

Hybrid nanoarchitectures are among the most promising nanotechnology-enabled materials for biomedical applications. Interfacing of nanoparticles with active materials gives rise to the structures with unique multiple functionality. Superparamagnetic iron oxide nanoparticles particles SPION are widely employed in the biology and in developing of advanced medical technologies. Polymeric micelles offer the advantage of multifunctional carriers which can serve as delivery vehicles carrying nanoparticles, hydrophobic chemotherapeutics and other functional materials and molecules. Stimuli-responsive polymers are especially attractive since their properties can be modulated in a controlled manner. Here we report on multifunctional thermo-responsive poly(N-isopropylacrylamide-co-acrylamide)-block-poly(ε-caprolactone) random block copolymer micelles as magnetic hyperthermia-mediated payload release and imaging agents. The combination of copolymers, nanoparticles and doxorubicin drug was tailored the way that the loaded micelles were cable to respond to magnetic heating at physiologically-relevant temperatures. A surface functionalization of the micelles with the integrin β4 antibody and consequent interfacing of the resulting nanobio hybrid with squamous head and neck carcinoma cells which is known to specifically over-express the A9 antigen resulted in concentration of the micelles on the surface of cells. No inherent cytotoxicity was detected for the magnetic micelles without external stimuli application. Furthermore, SPION-loaded micelles demonstrate significant MRI contrast enhancement abilities.

Assembly of polythiophenes on responsive polymer microgels for the highly selective detection of ammonia gas

DOE PAGES

Chang, Aiping; Peng, Yahui; Li, Zezhou; ...

2016-04-05

For this study, a class of smart composite materials based on the assembly of conjugated polymers on responsive polymer microgels has been prepared. We have chosen poly(3-((2-(2-methoxyethoxy)ethoxy)methyl)-thiophene) as the model conjugated polymer and an ammonia-responsive microgel of phenoxazinium-functionalized poly(N-isopropylacrylamide-co-propargyl acrylate) as the model template. Under this design, the composite materials can combine the electrical conductivity of the conjugated polymers and the ammonia recognisability of the ammonia-responsive polymer microgels; the cooperation of these properties allows the reversible control of electrical conductivity by ammonia gas. Those composite materials can not only adapt to ammonia gas, but also convert changes in the concentrationmore » of ammonia into conductance, allowing the electrical detection of ammonia gas with high selectivity. This makes the composite materials different from the conductive polymer platforms reported previously, which may also respond to non-ammonia gases and the response induced by non-ammonia gases is close to that induced by ammonia gas. Using these composite materials as sensing materials for the electrical detection of ammonia gas, the detection limit can reach as low as 1.1 ppb. Finally, these features enable their use for the electrical detection of ammonia in breath.« less

Assembly of polythiophenes on responsive polymer microgels for the highly selective detection of ammonia gas

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

Chang, Aiping; Peng, Yahui; Li, Zezhou

For this study, a class of smart composite materials based on the assembly of conjugated polymers on responsive polymer microgels has been prepared. We have chosen poly(3-((2-(2-methoxyethoxy)ethoxy)methyl)-thiophene) as the model conjugated polymer and an ammonia-responsive microgel of phenoxazinium-functionalized poly(N-isopropylacrylamide-co-propargyl acrylate) as the model template. Under this design, the composite materials can combine the electrical conductivity of the conjugated polymers and the ammonia recognisability of the ammonia-responsive polymer microgels; the cooperation of these properties allows the reversible control of electrical conductivity by ammonia gas. Those composite materials can not only adapt to ammonia gas, but also convert changes in the concentrationmore » of ammonia into conductance, allowing the electrical detection of ammonia gas with high selectivity. This makes the composite materials different from the conductive polymer platforms reported previously, which may also respond to non-ammonia gases and the response induced by non-ammonia gases is close to that induced by ammonia gas. Using these composite materials as sensing materials for the electrical detection of ammonia gas, the detection limit can reach as low as 1.1 ppb. Finally, these features enable their use for the electrical detection of ammonia in breath.« less

Tailoring the degradation rates of thermally responsive hydrogels designed for soft tissue injection by varying the autocatalytic potential.

PubMed

Zhu, Yang; Jiang, Hongbin; Ye, Sang-Ho; Yoshizumi, Tomo; Wagner, William R

2015-01-01

The ability to modulate the degradation properties of biomaterials such as thermally responsive hydrogels is desirable when exploring new therapeutic strategies that rely on the temporary presence of a placed scaffold or gel. Here we report a method of manipulating the absorption rate of a poly(N-isopropylacrylamide) ((poly(NIPAAm)) based hydrogel across a wide range (from 1 d to 5 mo) by small alterations in the composition. Relying upon the autocatalytic effect, the degradation of poly(NIPAAm-co-HEMA-co-MAPLA), (HEMA = 2-hydroxyethyl methacrylate; MAPLA = methacrylate-polylactide) was greatly accelerated by adding a fourth monomer methacrylic acid (MAA) at no more than 2 mol% to obtain poly(NIPAAm-co-HEMA-co-MAPLA-co-MAA) (pNHMMj) where j reflects the MAA molar % in the reactant mixture. MAA residue introduction decreased the pH inside the hydrogels and in surrounding buffered solutions. Accelerated degradation positively correlated with MAA content in pNHMMj polymers, putatively by the accelerated cleavage of MAPLA residues to raise the transition temperature of the polymer above body temperature. Physical properties including thermal transition behavior and initial mechanical strength did not vary significantly with MAA content. A rat hindlimb injection model generally reflected the in vitro observation that higher MAA content resulted in more rapid degradation and cellular infiltration. The strategy of tuning the degradation of thermally responsive hydrogels where degradation or solubilization is determined by their polyester components might be applied to other tissue engineering and regenerative medicine applications where designed biomaterial degradation behavior is needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Robust and underwater superoleophobic coating with excellent corrosion and biofouling resistance in harsh environments

NASA Astrophysics Data System (ADS)

Su, Mingji; Liu, Yong; Zhang, Yuhong; Wang, Zhiguo; Li, Yulin; He, Peixin

2018-04-01

Underwater superoleophobic surfaces are based on the surface with micro-/nanoscale roughness and hydration layer. But the self-cleaning surfaces are usually mechanically weak and will lose their underwater superoleophobicity when the surfaces are corroded or damaged. In this paper, to overcome these problems, the robust underwater superoleophobic coating (HN/ER-coating) has been fabricated successfully through MPS (methacryloxy propyl trimethoxyl silane)-SiO2/PNIPAM (N-isopropylacryamide) hybrid nanoparticles and epoxy resin (ER) via a simple solution-casting method. The SiO2/PNIPAM hybrid nanoparticles can enhance multiscale roughness and excellent abrasion-resistant property, and the epoxy resin can be used as an interlayer between hybrid nanoparticles and substrates to promote the robustness and corrosion resistance of the coating. The obtained coatings have excellent underwater superoleophobicity, and exhibit highly stability in harsh environments (including acid-base, strong ionic strength, mechanical abrasion). Moreover, this coating can provide protective effect on the substrate in corrosive solution, and may also resist bacterial attachment and subsequent biofilm formation because of the presence of high density PNIPAM polymers. Herein, the developed underwater superoleophobic coating can be applied as an effective platform for the applications in underwater instruments, underwater oil transport, marine oil platform and ships.

Spontaneous deswelling of pNIPAM microgels at high concentrations

NASA Astrophysics Data System (ADS)

Gasser, Urs; Scotti, Andrea; Herman, Emily S.; Pelaez-Fernandez, Miguel; Han, Jun; Menzel, Andreas; Lyon, L. Andrew; Fernandez-Nieves, Alberto

Polydisperse suspensions of pNIPAM microgel particles show a unique, spontaneous particle deswelling behavior. Beyond a critical concentration, the largest microgels deswell and thereby reduce the polydispersity of the suspension. We have recently unraveled the mechanism of this spontaneous, selective deswelling. pNIPAM microgels carry charged sulfate groups originating from the ammonium persulfate starter used in particle synthesis. Most of the ammonium counterions are trapped close to the microgel surface, but a fraction of them escapes the electrostatic attraction and contributes to the osmotic pressure of the suspension. The counterion clouds of neighboring particles progressively overlap with increasing volume fraction, leading to an increase of free counterions and the osmotic pressure outside but not inside the microgel particles. We find particles to deswell when the resulting osmotic pressure difference between the inside and the outside becomes larger their bulk modulus. For pNIPAM microgels synthesized with the same protocol, the largest particles are the softest and deswell first.

Stimuli Responsive Morphological Changes of Pnipa Polymer Brushes Synthesized on Silicon Substrate

NASA Astrophysics Data System (ADS)

Huda, Muhammad Nurul; Kabir, A. N. M. Hamidul

2013-08-01

High-density polymer brushes were grown from the silicon surface by atom transfer radical polymerization of Poly(N-isopropylacrylamide) (PNIPA) at different polymerization conditions. PNIPA brushes were prepared using Copper (I) Chloride/tris(2-(dimetylamino)ethyl)amine (Me6TREN) as a catalytic system in DMSO at 20°C. Free polymer formed during the brush formation was characterized by gel permeation chromatography. The grafting densities up to 0.52 chains/nm2 were obtained. The layer thickness of polymer brush increases with the increase of conversion of the monomer conversion as well as polymerization time. Atomic force microscopy and air bubble contact angle under pH solution were employed to study the surface morphology, reversible conformational changes of and stimulus-response behavior. PNIPA brushes exhibited a different nanomorphology after treatment with different pH solution. It also revealed a unique reversible wetting behavior with pH. The reversible properties of the PNIPA brushes can be used to regulate the adsorption of the sulfonated PS nanoparticles.

Functional lignocellulosic materials prepared by ATRP from a wood scaffold.

PubMed

Cabane, Etienne; Keplinger, Tobias; Künniger, Tina; Merk, Vivian; Burgert, Ingo

2016-08-10

Wood, a natural and abundant source of organic polymers, has been used as a scaffold to develop novel wood-polymer hybrid materials. Through a two-step surface-initiated Atom Transfer Radical Polymerization (ATRP), the porous wood structure can be effectively modified with polymer chains of various nature. In the present study, polystyrene and poly(N-isopropylacrylamide) were used. As shown with various characterization techniques including confocal Raman microscopy, FTIR, and SEM/EDX, the native wood ultrastructure and features are retained and the polymer chains can be introduced deep within the wood, i.e. inside the wood cell walls. The physical properties of the new materials have been studied, and results indicate that the insertion of polymer chains inside the wood cell wall alters the intrinsic properties of wood to yield a hybrid composite material with new functionalities. This approach to the functionalization of wood could lead to the fabrication of a new class of interesting functional materials and promote innovative utilizations of the renewable resource wood.

Thermosensitive polymer stabilized core-shell AuNR@Ag nanostructures as "smart" recyclable catalyst

NASA Astrophysics Data System (ADS)

Li, Dongxiang; Liu, Na; Gao, Yuanyuan; Lin, Weihong; Li, Chunfang

2017-11-01

Core-shell AuNR@Ag nanostructures were synthesized and surface-grafted with thermosensitive poly( N-isopropylacrylamide) to enhance stability and endow stimuli-responsive property. The AuNR cores showed average dimensions of 8-nm diameter and 33-nm length, while the anisotropic silver shells displayed 1-2 nm thin side and maximal 8 nm fat side. The obtained polymer-stabilized AuNR@Ag nanostructures as catalysts showed normal Arrhenius change of apparent rate constant, k app, in catalyzed reaction between 20 and 30 °C, but displayed a decrease of k app with respect to the temperature increasing between 32.5-40 °C, showing self-inhibition of the observed catalytic activity. Such "smart" self-inhibition of catalytic activity at enhanced temperature can be attributed to the thermosensitive response of the grafted polymer molecules and should be significant to control the reaction rate and avoid superheat for exothermic reactions. Such polymer-stabilized nanocatalyst also could be recovered and reused in the catalytic system. [Figure not available: see fulltext.

Large deformation of self-oscillating polymer gel

NASA Astrophysics Data System (ADS)

Maeda, Shingo; Kato, Terukazu; Otsuka, Yuji; Hosoya, Naoki; Cianchetti, Matteo; Laschi, Cecilia

2016-01-01

A self-oscillating gel is a system that generates an autonomous volume oscillation. This oscillation is powered by the chemical energy of the Belousov-Zhabotinsky (BZ) reaction, which demonstrates metal ion redox oscillation. A self-oscillating gel is composed of Poly-N -isopropylacrylamide (PNIPAAm) with a metal ion. In this study, we found that the displacement of the volume oscillation in a self-oscillating gel could be controlled by its being subjected to a prestraining process. We also revealed the driving mechanism of the self-oscillating gel from the point of view of thermodynamics. We observed that the polymer-solvent interaction parameter χ is altered by the redox changes to the metal ion incorporated in the self-oscillating gel. The prestraining process leads to changes in χ and changes in enthalpy and entropy when the self-oscillating gel is in a reduced and oxidized state. We found that nonprestrained gel samples oscillate in a poor solution (χ >0.5 ) and prestrained gel samples oscillate in a good solution (χ <0.5 ).

Recognition-Mediated Hydrogel Swelling Controlled by Interaction with a Negative Thermoresponsive LCST Polymer.

PubMed

Belal, Khaled; Stoffelbach, François; Lyskawa, Joël; Fumagalli, Matthieu; Hourdet, Dominique; Marcellan, Alba; Smet, Lieselot De; de la Rosa, Victor R; Cooke, Graeme; Hoogenboom, Richard; Woisel, Patrice

2016-11-02

Most polymeric thermoresponsive hydrogels contract upon heating beyond the lower critical solution temperature (LCST) of the polymers used. Herein, we report a supramolecular hydrogel system that shows the opposite temperature dependence. When the non-thermosesponsive hydrogel NaphtGel, containing dialkoxynaphthalene guest molecules, becomes complexed with the tetra cationic macrocyclic host CBPQT 4+ , swelling occurred as a result of host-guest complex formation leading to charge repulsion between the host units, as well as an osmotic contribution of chloride counter-ions embedded in the network. The immersion of NaphtGel in a solution of poly(N-isopropylacrylamide) with tetrathiafulvalene (TTF) end groups complexed with CBPQT 4+ induced positive thermoresponsive behaviour. The LCST-induced dethreading of the polymer-based pseudorotaxane upon heating led to transfer of the CBPQT 4+ host and a concomitant swelling of NaphtGel. Subsequent cooling led to reformation of the TTF-based host-guest complexes in solution and contraction of the hydrogel. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Functional lignocellulosic materials prepared by ATRP from a wood scaffold

PubMed Central

Cabane, Etienne; Keplinger, Tobias; Künniger, Tina; Merk, Vivian; Burgert, Ingo

2016-01-01

Wood, a natural and abundant source of organic polymers, has been used as a scaffold to develop novel wood-polymer hybrid materials. Through a two-step surface-initiated Atom Transfer Radical Polymerization (ATRP), the porous wood structure can be effectively modified with polymer chains of various nature. In the present study, polystyrene and poly(N-isopropylacrylamide) were used. As shown with various characterization techniques including confocal Raman microscopy, FTIR, and SEM/EDX, the native wood ultrastructure and features are retained and the polymer chains can be introduced deep within the wood, i.e. inside the wood cell walls. The physical properties of the new materials have been studied, and results indicate that the insertion of polymer chains inside the wood cell wall alters the intrinsic properties of wood to yield a hybrid composite material with new functionalities. This approach to the functionalization of wood could lead to the fabrication of a new class of interesting functional materials and promote innovative utilizations of the renewable resource wood. PMID:27506369

Purification of anti-bromelain antibodies by affinity precipitation using pNIPAm-linked bromelain.

PubMed

Mahmood, Rubab

2016-01-01

Affinity precipitation has emerged as a very useful technique for the purification of proteins. Here it has been employed for the purification of anti-bromelain antibodies from rabbit serum. A system has been developed for reversibly binding and thermoprecipitating antibodies. Anti-bromelain antibodies were raised in rabbit by immunizing it with bromelain. Poly-N-isopropylacrylamide (pNIPAm)-bromelain conjugate was prepared and incubated with rabbit serum. After that the temperature was raised for thermal precipitation of the polymer. Antibodies were then eluted from the complex by incubating it with a small volume of buffer, pH 3.0. This method is very effective in concentrating the antibodies. Purity and specificity of the antibodies were checked by gel electrophoresis and enzyme-linked immunosorbent assay (ELISA), respectively. The study of the effect of pH and temperature on the binding of the antibodies to the conjugate showed that the optimum binding occurred at pH 8.0 and 25°C.The polymer enzyme conjugate was further used for another cycle.

New generation ICG-based contrast agents for ultrasound-switchable fluorescence imaging

PubMed Central

Yu, Shuai; Cheng, Bingbing; Yao, Tingfeng; Xu, Cancan; Nguyen, Kytai T.; Hong, Yi; Yuan, Baohong

2016-01-01

Recently, we developed a new technology, ultrasound-switchable fluorescence (USF), for high-resolution imaging in centimeter-deep tissues via fluorescence contrast. The success of USF imaging highly relies on excellent contrast agents. ICG-encapsulated poly(N-isopropylacrylamide) nanoparticles (ICG-NPs) are one of the families of the most successful near-infrared (NIR) USF contrast agents. However, the first-generation ICG-NPs have a short shelf life (<1 month). This work significantly increases the shelf life of the new-generation ICG-NPs (>6 months). In addition, we have conjugated hydroxyl or carboxyl function groups on the ICG-NPs for future molecular targeting. Finally, we have demonstrated the effect of temperature-switching threshold (Tth) and the background temperature (TBG) on the quality of USF images. We estimated that the Tth of the ICG-NPs should be controlled at ~38–40 °C (slightly above the body temperature of 37 °C) for future in vivo USF imaging. Addressing these challenges further reduces the application barriers of USF imaging. PMID:27775014

The Preparation and Simple Analysis of a Clay Nanoparticle Composite Hydrogel

ERIC Educational Resources Information Center

Warren, David S.; Sutherland, Sam P. H.; Kao, Jacqueline Y.; Weal, Geoffrey R.; Mackay, Sean M.

2017-01-01

Samples of a composite hydrogel incorporating clay (Laponite XLG and S-482) nanoparticles were prepared using N-isopropylacrylamide. The hydrogels were formed via a radical-initiated addition polymerization using potassium persulfate and N,N,N',N'-tetramethylethylenediamine. Students then measured the force required to stretch the gels and…

Self-Assembly of Colloidal Photonic Crystals of PS@PNIPAM Nanoparticles and Temperature-Responsive Tunable Fluorescence.

PubMed

Yuan, Shuai; Ge, Fengyan; Yang, Xue; Guang, Shanyi

2016-11-01

A strategy for significantly enhancing fluorescence is developed based on the coupling of optical properties of colloidal photonic crystals (CPCs) with responsive microgel. In this paper, thermoresponsive microgel PNIPAM was employed for the fabrication of core-shell structure. The core-shell PS@PNIPAM nanoparticles (NPs) are then assembled to CPCs by a vertical deposition method. Subsequently, the novel functional material (RhB/CPCs) can be prepared by depositing fluorescent dye molecules (RhB) on the top of PS@PNIPAM CPCs. We obtained an increase in the fluorescent intensity up to 15-fold and 22-fold compared with RhB on the glass slid and the uneven film. Due to the unique responsive shrinking properties of PNIPAM shell, the amplifying fluorescence behavior of CPCs can be well tuned by varying the temperature. In contrast to RhB on the glass slid, a 15-fold and 12-fold fluorescence enhancement can be observed when the temperature of RhB/CPCs was 20 °C and 50 °C, respectively. The mechanism on enhancement fluorescence of tunable CPCs can be achieved by measurements of thermoresponsive properties. The results indicate that the responsive fluorescence-amplifying method based on CPCs made with responsive core-shell NPs has a potential application for the development of efficient fluorescence sensors.

Surface interaction forces of cellulose nanocrystals grafted with thermoresponsive polymer brushes.

PubMed

Zoppe, Justin O; Osterberg, Monika; Venditti, Richard A; Laine, Janne; Rojas, Orlando J

2011-07-11

The colloidal stability and thermoresponsive behavior of poly(N-isopropylacrylamide) brushes grafted from cellulose nanocrystals (CNCs) of varying graft densities and molecular weights was investigated. Indication of the grafted polymer brushes was obtained after AFM imaging of CNCs adsorbed on silica. Also, aggregation of the nanoparticles carrying grafts of high degree of polymerization was observed. The responsiveness of grafted CNCs in aqueous dispersions and as an ultrathin film was evaluated by using light scattering, viscosimetry, and colloidal probe microscopy (CPM). Light transmittance measurements showed temperature-dependent aggregation originating from the different graft densities and molecular weights. The lower critical solution temperature (LCST) of grafted poly(NiPAAm) brushes was found to decrease with the ionic strength, as is the case for free poly(NiPAAm) in aqueous solution. Thermal responsive behavior of grafted CNCs in aqueous dispersions was observed by a sharp increase in dispersion viscosity as the temperature approached the LCST. CPM in liquid media for asymmetric systems consisting of ultrathin films of CNCs and a colloidal silica probe showed the distinctive effects of the grafted polymer brushes on interaction and adhesive forces. The origin of such forces was found to be mainly electrostatic and steric in the case of bare and grafted CNCs, respectively. A decrease in the onset of attractive and adhesion forces of grafted CNCs films were observed with the ionic strength of the aqueous solution. The decreased mobility of polymer brushes upon partial collapse and decreased availability of hydrogen bonding sites with higher electrolyte concentration were hypothesized as the main reasons for the less prominent polymer bridging between interacting surfaces.

Hierarchically Self-Assembled Supramolecular Host-Guest Delivery System for Drug Resistant Cancer Therapy.

PubMed

Cheng, Hongwei; Fan, Xiaoshan; Wang, Xiaoyuan; Ye, Enyi; Loh, Xian Jun; Li, Zibiao; Wu, Yun-Long

2018-06-11

In this report, a new star-like copolymer β-CD- g-(PNIPAAm- b-POEGA) x , consisting of a β-CD core, grafted with temperature-responsive poly( N-isopropylacrylamide) (PNIPAAm) and biocompatible poly(oligo(ethylene glycol) acrylate) (POEGA) in a block copolymer of the arms, was used to deliver chemotherapeutics to drug resistant cancer cells and tumors. The first step of the self-assembly process involves the encapsulation of chemotherapeutics through host-guest inclusion complexation between the β-cyclodextrin cavity and the anticancer drug. Next, the chain interaction of the PNIPAAm segment at elevated temperature drives the drug-loaded β-CD- g-(PNIPAAm- b-POEGA) x /PTX inclusion complex to hierarchically self-assemble into nanosized supramolecular assemblies at 37 °C, whereas the presence of poly(ethylene glycol) (PEG) chains in the distal end of the star-like copolymer arms impart enhanced stability to the self-assembled structure. More interestingly, this supramolecular host-guest nanocomplex promoted the enhanced cellular uptake of chemotherapeutics in MDR-1 up-regulated drug resistant cancer cells and exhibited high therapeutic efficacy for suppressing drug resistant tumor growth in an in vivo mouse model, due to the increased stability, improvement in aqueous solubility, enhanced cellular uptake, and partial membrane pump impairment by taking the advantage of PEGylation and supramolecular complex between this star-like copolymer and chemotherapeutics. This work signifies that temperature-sensitive PEGylated supramolecular nanocarriers with good biocompatibility are effective in combating MDR-1 mediated drug resistance in both in vitro and in vivo models, which is of significant importance for the advanced drug delivery platform designed to combat drug resistant cancer.

A smart core-sheath nanofiber that captures and releases red blood cells from the blood

NASA Astrophysics Data System (ADS)

Shi, Q.; Hou, J.; Zhao, C.; Xin, Z.; Jin, J.; Li, C.; Wong, S.-C.; Yin, J.

2016-01-01

A smart core-sheath nanofiber for non-adherent cell capture and release is demonstrated. The nanofibers are fabricated by single-spinneret electrospinning of poly(N-isopropylacrylamide) (PNIPAAm), polycaprolactone (PCL) and nattokinase (NK) solution blends. The self-assembly of PNIPAAm and PCL blends during the electrospinning generates the core-sheath PCL/PNIPAAm nanofibers with PNIPAAm as the sheath. The PNIPAAm-based core-sheath nanofibers are switchable between hydrophobicity and hydrophilicity with temperature change and enhance stability in the blood. When the nanofibers come in contact with blood, the NK is released from the nanofibers to resist platelet adhesion on the nanofiber surface, facilitating the direct capture and isolation of red blood cells (RBCs) from the blood above phase-transition temperature of PNIPAAm. Meanwhile, the captured RBCs are readily released from the nanofibers with temperature stimuli in an undamaged manner. The release efficiency of up to 100% is obtained while maintaining cellular integrity and function. This work presents promising nanofibers to effectively capture non-adherent cells and release for subsequent molecular analysis and diagnosis of single cells.A smart core-sheath nanofiber for non-adherent cell capture and release is demonstrated. The nanofibers are fabricated by single-spinneret electrospinning of poly(N-isopropylacrylamide) (PNIPAAm), polycaprolactone (PCL) and nattokinase (NK) solution blends. The self-assembly of PNIPAAm and PCL blends during the electrospinning generates the core-sheath PCL/PNIPAAm nanofibers with PNIPAAm as the sheath. The PNIPAAm-based core-sheath nanofibers are switchable between hydrophobicity and hydrophilicity with temperature change and enhance stability in the blood. When the nanofibers come in contact with blood, the NK is released from the nanofibers to resist platelet adhesion on the nanofiber surface, facilitating the direct capture and isolation of red blood cells (RBCs) from the blood above phase-transition temperature of PNIPAAm. Meanwhile, the captured RBCs are readily released from the nanofibers with temperature stimuli in an undamaged manner. The release efficiency of up to 100% is obtained while maintaining cellular integrity and function. This work presents promising nanofibers to effectively capture non-adherent cells and release for subsequent molecular analysis and diagnosis of single cells. Electronic supplementary information (ESI) available: Electrospinning of polymer nanofibers; FTIR spectra and XPS spectra of PCL, PNIPAAm and PCL/PNIPAAm nanofibers; SEM images of PCL/PNIPAAm nanofibers with varied composition; PNIPAAm content on the sheath of nanofibers; stability of core-sheath PCL/PNIPAAm nanofibers. Platelet adhesion on the PCL/PNIPAAm nanofibers in the presence of NK; Protein adsorption on nanofibers. See DOI: 10.1039/c5nr07070h

Magnetic/NIR-thermally responsive hybrid nanogels for optical temperature sensing, tumor cell imaging and triggered drug release

NASA Astrophysics Data System (ADS)

Wang, Hui; Yi, Jinhui; Mukherjee, Sumit; Banerjee, Probal; Zhou, Shuiqin

2014-10-01

The paper demonstrates a class of multifunctional core-shell hybrid nanogels with fluorescent and magnetic properties, which have been successfully developed for simultaneous optical temperature sensing, tumor cell imaging and magnetic/NIR-thermally responsive drug carriers. The as-synthesized hybrid nanogels were designed by coating bifunctional nanoparticles (BFNPs, fluorescent carbon dots embedded in the porous carbon shell and superparamagnetic iron oxide nanocrystals clustered in the core) with a thermo-responsive poly(N-isopropylacrylamide-co-acrylamide) [poly(NIPAM-AAm)]-based hydrogel as the shell. The BFNPs in hybrid nanogels not only demonstrate excellent photoluminescence (PL) and photostability due to the fluorescent carbon dots embedded in the porous carbon shell, but also has targeted drug accumulation potential and a magnetic-thermal conversion ability due to the superparamagnetic iron oxide nanocrystals clustered in the core. The thermo-responsive poly(NIPAM-AAm)-based gel shell can not only modify the physicochemical environment of the BFNPs core to manipulate the fluorescence intensity for sensing the variation of the environmental temperature, but also regulate the release rate of the loaded anticancer drug (curcumin) by varying the local temperature of environmental media. In addition, the carbon layer of BFNPs can adsorb and convert the NIR light to heat, leading to a promoted drug release under NIR irradiation and improving the therapeutic efficacy of drug-loaded hybrid nanogels. Furthermore, the superparamagnetic iron oxide nanocrystals in the core of BFNPs can trigger localized heating using an alternating magnetic field, leading to a phase change in the polymer gel to trigger the release of loaded drugs. Finally, the multifunctional hybrid nanogels can overcome cellular barriers to enter the intracellular region and light up the mouse melanoma B16F10 cells. The demonstrated hybrid nanogels would be an ideal system for the biomedical applications due to their excellent optical properties, magnetic properties, high drug loading capacity and responsive drug release behavior.The paper demonstrates a class of multifunctional core-shell hybrid nanogels with fluorescent and magnetic properties, which have been successfully developed for simultaneous optical temperature sensing, tumor cell imaging and magnetic/NIR-thermally responsive drug carriers. The as-synthesized hybrid nanogels were designed by coating bifunctional nanoparticles (BFNPs, fluorescent carbon dots embedded in the porous carbon shell and superparamagnetic iron oxide nanocrystals clustered in the core) with a thermo-responsive poly(N-isopropylacrylamide-co-acrylamide) [poly(NIPAM-AAm)]-based hydrogel as the shell. The BFNPs in hybrid nanogels not only demonstrate excellent photoluminescence (PL) and photostability due to the fluorescent carbon dots embedded in the porous carbon shell, but also has targeted drug accumulation potential and a magnetic-thermal conversion ability due to the superparamagnetic iron oxide nanocrystals clustered in the core. The thermo-responsive poly(NIPAM-AAm)-based gel shell can not only modify the physicochemical environment of the BFNPs core to manipulate the fluorescence intensity for sensing the variation of the environmental temperature, but also regulate the release rate of the loaded anticancer drug (curcumin) by varying the local temperature of environmental media. In addition, the carbon layer of BFNPs can adsorb and convert the NIR light to heat, leading to a promoted drug release under NIR irradiation and improving the therapeutic efficacy of drug-loaded hybrid nanogels. Furthermore, the superparamagnetic iron oxide nanocrystals in the core of BFNPs can trigger localized heating using an alternating magnetic field, leading to a phase change in the polymer gel to trigger the release of loaded drugs. Finally, the multifunctional hybrid nanogels can overcome cellular barriers to enter the intracellular region and light up the mouse melanoma B16F10 cells. The demonstrated hybrid nanogels would be an ideal system for the biomedical applications due to their excellent optical properties, magnetic properties, high drug loading capacity and responsive drug release behavior. Electronic supplementary information (ESI) available: Fig. S1-S12. See DOI: 10.1039/c4nr03748k

Small Angle Neutron Scattering Study in Multi-Component Polymer Systems: Spinodal Decomposition and Beyond

NASA Astrophysics Data System (ADS)

Han, Charles

Institute for Advanced Study, Shenzhen University, Shenzhen, China In memory of Professor John Kohn at this symposium, a time resolved SANS study for the early stage of spinodal decomposition kinetics of deuterated polycarbonate/poly(methylmethacrylate) blend will be reviewed which gives a clear proof of the Cahn-Hillard-Cook theory. This early stage of spinodal decomposition kinetics has been observed starting from the dimension (q-l) comparable to the single chain radius of gyration, Rg\\ , for a binary polymer mixture. The results provide an unequivocal quantitative measure of the virtual structure factor, S (q, ∞); the relationship of qm and qc through rate of growth, Cahn-plot analysis, and singularity in S (q, ∞); the growth of fluctuation of qRg <1 and intra-chain relaxation of qRg >1. More recent study of using mixed suspensions of polystyrene microspheres and poly(N-isopropylacrylamide) microgels as a molecular model system which has a long range repulsive interaction potential and a short range attractive potential, will also be discussed. In this model system, dynamic gelation, transition to soft glass state and cross-over to hard glass state will be demonstrated and compared with available theories for glass transition in structural materials. Acknowledgements go to: Polymers Division, and NCNR of NIST, and to ICCAS, Beijing, China. Also to my colleagues: M. Motowoka, H. Jinnai, T. Hashimoto, G.C. Yuan and H. Cheng.

In situ spray deposition of cell-loaded, thermally and chemically gelling hydrogel coatings for tissue regeneration.

PubMed

Pehlivaner Kara, Meryem O; Ekenseair, Adam K

2016-10-01

In this study, the efficacy of creating cellular hydrogel coatings on warm tissue surfaces through the minimally invasive, sprayable delivery of thermoresponsive liquid solutions was investigated. Poly(N-isopropylacrylamide)-based (pNiPAAm) thermogelling macromers with or without addition of crosslinking polyamidoamine (PAMAM) macromers were synthesized and used to produce in situ forming thermally and chemically gelling hydrogel systems. The effect of solution and process parameters on hydrogel physical properties and morphology was evaluated and compared to poly(ethylene glycol) and injection controls. Smooth, fast, and conformal hydrogel coatings were obtained when pNiPAAm thermogelling macromers were sprayed with high PAMAM concentration at low pressure. Cellular hydrogel coatings were further fabricated by different spraying techniques: single-stream, layer-by-layer, and dual stream methods. The impact of spray technique, solution formulation, pressure, and spray solution viscosity on the viability of fibroblast and osteoblast cells encapsulated in hydrogels was elucidated. In particular, the early formation of chemically crosslinked micronetworks during bulk liquid flow was shown to significantly affect cell viability under turbulent conditions compared to injectable controls. The results demonstrated that sprayable, in situ forming hydrogels capable of delivering cell populations in a homogeneous therapeutic coating on diseased tissue surfaces offer promise as novel therapies for applications in regenerative medicine. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2383-2393, 2016. © 2016 Wiley Periodicals, Inc.

A novel multi-responsive polyampholyte composite hydrogel with excellent mechanical strength and rapid shrinking rate.

PubMed

Xu, Kun; Tan, Ying; Chen, Qiang; An, Huiyong; Li, Wenbo; Dong, Lisong; Wang, Pixin

2010-05-15

Series of hydrophilic core-shell microgels with cross-linked poly(N-isopropylacrylamide) (PNIPAAm) as core and poly(vinyl amine) (PVAm) as shell are synthesized via surfactant-free emulsion polymerization. Then, the microgels are treated with a small amount of potassium persulfate (KPS) to generate free radicals on the amine nitrogens of PVAm, which subsequently initiate the graft copolymerization of acrylic acid (AA), acryloyloxyethyl trimethyl ammonium chloride (DAC), and acrylamide (AAm) onto microgels to prepare multi-responsive composite hydrogels. The composite hydrogels consist of cross-linked ungrafted polyampholyte chains as the first network and microgels with grafted polyampholyte chains as graft point and second network and show surprising mechanical strength and rapid response rate. The investigation shows the compress strength of composite hydrogels is up to 17-30 MPa, which is 60-100 times higher than that of the hydrogel matrix. The composite hydrogel shows reversible switch of transmittance when traveling the lowest critical temperature (LCST) of microgels. When the composite hydrogel swollen in pH 2.86 solution at ambient condition is immersed into the pH 7.00 solution at 45 °C, a rapid dynamic shrinking can be observed. And the character time (τ) of shrinking dynamic of composite hydrogel is 251.9 min, which is less than that of hydrogel matrix (τ=2273.7 min). Copyright © 2010 Elsevier Inc. All rights reserved.

The effects of cross-linked thermo-responsive PNIPAAm-based hydrogel injection on retinal function.

PubMed

Turturro, Sanja B; Guthrie, Micah J; Appel, Alyssa A; Drapala, Pawel W; Brey, Eric M; Pérez-Luna, Victor H; Mieler, William F; Kang-Mieler, Jennifer J

2011-05-01

There is significant interest in biomaterials that provide sustained release of therapeutic molecules to the retina. Poly(N-isopropylacrylamide) (PNIPAAm)-based materials have received significant attention as injectable drug delivery platforms due to PNIPAAm's thermo-responsive properties at approximately 32 °C. While the drug delivery properties of PNIPAAm materials have been studied extensively, there is a need to evaluate the safety effects of hydrogel injection on retinal function. The purpose of this study was to examine the effect of poly(ethylene glycol) diacrylate (PEG-DA) crosslinked PNIPAAm hydrogel injection on retinal function. Utilizing scanning laser ophthalmoscopy (SLO), optical coherent tomography (OCT), and electroretinography (ERG), retinal function was assessed following hydrogel injection. In region near the hydrogel, there was a significant decrease in arterial and venous diameters (∼4%) and an increase in venous blood velocity (∼8%) 1 week post-injection. Retinal thickness decreased (∼6%) at 1 week and the maximum a- and b-wave amplitudes of ERG decreased (∼15%). All data returned to baseline values after week 1. These data suggest that the injection of PEG-DA crosslinked PNIPAAm hydrogel results in a small transient effect on retinal function without any long-term effects. These results further support the potential of PNIPAAm-based materials as an ocular drug delivery platform. Copyright © 2011 Elsevier Ltd. All rights reserved.

Preparation of thermo-responsive graft copolymer by using a novel macro-RAFT agent and its application for drug delivery.

PubMed

Song, Cunfeng; Yu, Shirong; Liu, Cheng; Deng, Yuanming; Xu, Yiting; Chen, Xiaoling; Dai, Lizong

2016-05-01

A methodology to prepare thermo-responsive graft copolymer by using a novel macro-RAFT agent was proposed. The macro-RAFT agent with pendant dithioester (ZC(S)SR) was facilely prepared via the combination of RAFT polymerization and esterification reaction. By means of ZC(S)SR-initiated RAFT polymerization, the thermo-responsive graft copolymer consisting of poly(methyl methacrylate-co-hydroxylethyl methacrylate) (P(MMA-co-HEMA)) backbone and hydrophilic poly(N-isopropylacrylamide) (PNIPAAm) side chains was constructed through the "grafting from" approach. The chemical compositions and molecular weight distributions of the synthesized polymers were respectively characterized by (1)H nuclear magnetic resonance ((1)H NMR) and gel permeation chromatography (GPC). Self-assembly behavior of the amphiphilic graft copolymers (P(MMA-co-HEMA)-g-PNIPAAm) was studied by transmission electron microscopy (TEM), dynamic light scattering (DLS) and spectrofluorimeter. The critical micelle concentration (CMC) value was 0.052 mg mL(-1). These micelles have thermo-responsibility and a low critical solution temperature (LCST) of 33.5°C. Further investigation indicated that the guest molecule release property of these micelles, which can be well described by a first-order kinetic model, was significantly affected by temperature. Besides, the micelles exhibited excellent biocompatibility and cellular uptake property. Hence, these micelles are considered to have potential application in controlled drug delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Novel thermosensitive polymeric micelles for docetaxel delivery.

PubMed

Yang, Mi; Ding, Yitao; Zhang, Leyang; Qian, Xiaoping; Jiang, Xiqun; Liu, Baorui

2007-06-15

Targeted delivery of antitumor drugs triggered by hyperthermia has significant advantages in clinical applications, since it is easy to implement and side effects are reduced. To release drugs site-specifically upon local heating often requires the drugs to be loaded into a thermosensitive polymer matrix with a low critical solution temperature (LCST) between 37 and 42 degrees C. However, the LCSTs of most thermosensitive materials were below 37 degrees C, which limits their application in clinic because they would precipitate once injected into human body and lost thermal targeting function. Herein, we prepared a novel thermosensitive copolymer (poly(N-isopropylacrylamide-co-acrylamide)-b-poly (DL-lactide)) that exhibits no obvious physical change up to 41 degrees C when heated. Docetaxel loaded micelles made of such thermosensitive polymer were prepared by dialysis method and the maximum loading content was found to be up to 27%. The physical properties, such as structure, morphology, and size distribution of the micelles with and without docetaxel were investigated by NMR, X-ray diffraction, dynamic light scattering, atomic force microscopy, etc. The efficacy of this drug delivery system was also evaluated by examining the proliferation inhibiting activity against different cell lines in vitro. After hyperthermia, the cytotoxicity of docetaxel-loaded micelles increased prominently. Our results demonstrated that this copolymer could be an ideal candidate for thermal targeted antitumor drug delivery. (c) 2007 Wiley Periodicals, Inc.

Mixed-Matrix Membranes Containing Carbon Nanotubes Composite with Hydrogel for Efficient CO2 Separation.

PubMed

Zhang, Haiyang; Guo, Ruili; Hou, Jinpeng; Wei, Zhong; Li, Xueqin

2016-10-26

In this study, a carbon nanotubes composite coated with N-isopropylacrylamide hydrogel (NIPAM-CNTs) was synthesized. Mixed-matrix membranes (MMMs) were fabricated by incorporating NIPAM-CNTs composite filler into poly(ether-block-amide) (Pebax MH 1657) matrix for efficient CO 2 separation. The as-prepared NIPAM-CNTs composite filler mainly plays two roles: (i) The extraordinary smooth one-dimensional nanochannels of CNTs act as the highways to accelerate CO 2 transport through membranes, increasing CO 2 permeability; (ii) The NIPAM hydrogel layer coated on the outer walls of CNTs acts as the super water absorbent to increase water content of membranes, appealing both CO 2 permeability and CO 2 /gas selectivity. MMM containing 5 wt % NIPAM-CNTs exhibited the highest CO 2 permeability of 567 barrer, CO 2 /CH 4 selectivity of 35, and CO 2 /N 2 selectivity of 70, transcending 2008 Robeson upper bound line. The improved CO 2 separation performance of MMMs is mainly attributed to the construction of the efficient CO 2 transport pathways by NIPAM-CNTs. Thus, MMMs incorporated with NIPAM-CNTs composite filler can be used as an excellent membrane material for efficient CO 2 separation.

The conductivity measurements applied for the evaluation of controlled release of chlorhexidine from thermosensitive N-isopropylacrylamide derivative microgels.

PubMed

Musiał, Witold; Kokol, Vanja; Voncina, Bojana

2009-01-01

The aim of the work was the evaluation of the conductivity changes in aqueous environment, consisting of chlorhexidine, and N-isopropylacrylamide derivative microgel, during increasing the temperature between 25 degrees C and 42 degrees C, as a prerequisite to develop the this microgel for controlled release of chlorhexidine, when alterations in temperature are involved. Conductivity of studied systems underwent specific alterations, when temperature increased. For the system with polymer PNM I the values of conductivity were in the range 104,47 microS/cm - 134,70 microS/ cm, for temperature range 25 degrees C and 42 degrees C. In the case of PNM II - CX system, respective values reached 91,75 microS/cm - 135,95 microS/cm. The lowest conductivity values were observed when PNM III - CX mixture was studied: 96,90 microS/cm and 117,37 microS/cm. When a complex of derivatives of N-isopropylacrylamide with chlorhexidine undergoes thermal alteration, there is a potential to obtain controlled release of chlorhexidine from the polymeric bead in the range between 25 degrees C and 42 degrees C. The affinity of chlorhexidine to the polymer may be assessed in this systems applying the conductivity measurements. The solubility of chlorhexidine in the polymeric systems should be in future evaluated, to determine role of this factor in the conductivity alterations.

Thermo- and pH-responsive polymer brushes-grafted gigaporous polystyrene microspheres as a high-speed protein chromatography matrix.

PubMed

Qu, Jian-Bo; Xu, Yu-Liang; Liu, Jun-Yi; Zeng, Jing-Bin; Chen, Yan-Li; Zhou, Wei-Qing; Liu, Jian-Guo

2016-04-08

Dual thermo- and pH-responsive chromatography has been proposed using poly(N-isopropylacrylamide-co-butyl methacrylate-co-N,N-dimethylaminopropyl acrylamide) (P(NIPAM-co-BMA-co-DMAPAAM)) brushes grafted gigaporous polystyrene microspheres (GPM) as matrix. Atom transfer radical polymerization (ATRP) initiator was first coupled onto GPM through Friedel-Crafts acylation with 2-bromoisobutyryl bromide. The dual-responsive polymer brushes were then grafted onto GPM via surface-initiated ATRP. The surface composition, gigaporous structure, protein adsorption and dual-responsive chromatographic properties of the matrix (GPM-P(NIPAM-co-BMA-co-DMAPAAM) were characterized in detail. Results showed that GPM were successfully grafted with thermoresponsive cationic polymer brushes and that the gigaporous structure was well maintained. A column packed with GPM-P(NIPAM-co-BMA-co-DMAPAAM presented low backpressure, good permeability and appreciable thermo-responsibility. By changing pH of the mobile phase and temperature of the column in turn, the column can separate three model proteins at the mobile phase velocity up to 2528cmh(-1). A separation mechanism of this matrix was also proposed. All results indicate that the dual thermo- and pH-responsive chromatography matrix has great potentials in 'green' high-speed protein chromatography. Copyright © 2016 Elsevier B.V. All rights reserved.

Thermo-activated nano-material for use in optical devices

NASA Astrophysics Data System (ADS)

Mias, Solon; Sudor, Jan; Camon, Henri

2007-05-01

In this paper we describe the use of thermo-activated PNIPAM nano-material in optical switching devices. In other publications, the PNIPAM is used either as a carrier for crystalline colloidal array self-assemblies or as micro-particles that serve as pigment bags. In this publication we use a simpler-to-fabricate pure PNIPAM solution in a semi-dilute regime. The PNIPAM devices produced are transparent at temperatures below a critical temperature of 32°C and become diffusing above this temperature. We show that at 632nm the transmission through the devices is about 75% in the transparent state while the additional attenuation achieved in the diffusing state is of the order of 38 dB. The experimental fall and rise times obtained are large (about 300ms and 5s respectively) due to the non-optimised thermal addressing scheme. In addition, spectral measurements taken in the infrared spectrum (700-1000nm) demonstrate that the cell response is flat over a large portion of the infrared spectrum in both the transparent and the diffusing states.

Design of nanoengineered hybrid PVA/PNIPAm/CaCl2/SiO2-Polystyrene (PSt) colloidal crystal hydrogel coatings that sweat/rehydrate H2O from the atmosphere to give sustainable cooling and self-indicate their state

NASA Astrophysics Data System (ADS)

Eloi, Jean-Charles; Worsley, Myles P.; Sermon, Paul A.; Healy, William; Dimech, Christine

2016-09-01

The potential for nanoengineering hybrid PVA hydrogel and hydrogel microsphere optical coatings is demonstrated with fine-tuning by the addition of (i) PNIPAm domains, (ii) water-hunting humectant CaCl2, and (ii) polystyrene or SiO2 colloidal crystals. The design and application onto substrates of the hydrogel scaffold is described. The addition of a temperature-triggered component as well as humectant and NIR reflectors are reported. The hybrid hydrogels appeared effective in sustainable adsorption cooling technology (ACT) over sustained periods. It is shown that the thermoresponsive (PNIPAm) domains act as an extra reserve, sweating water above 305K, prolonging the controlled release of water. It is also reported that the addition of humectant is crucial for the natural re-hydration of the hydrogels. For the moment PNIPAm microspheres have only short- lived ACT properties. Finally, coating with microspheres (MSs) in hydrogels produces a visible-NIR reflector effect that may allow optical feedback on ACT.

N-isopropylacrylamide-based fine-dispersed thermosensitive ferrogels obtained via in-situ technique.

PubMed

Korotych, O; Samchenko, Yu; Boldeskul, I; Ulberg, Z; Zholobak, N; Sukhodub, L

2013-03-01

Thermosensitive hydrogels with magnetic properties (ferrogels) are very promising for medical application, first of all, for the design of targeted delivery systems with controlled release of drugs and for magnetic hyperthermia and chemotherapy treatment of cancer. These magnetic hydrogels could be obtained using diverse techniques: ex- and in-situ syntheses. The present work is devoted to the study of magnetite (Fe(3)O(4)) formation inside the nanoreactors of (co)polymeric hydrogels. Polymeric templates (hydrogel films and fine-dispersed hydrogels) used for obtaining ferrogels were based on acrylic monomers: thermosensitive N-isopropylacrylamide, and hydrophilic acrylamide. Covalent cross-linking was accomplished using bifunctional monomer N,N'-methylenebisacrylamide. Influence of hydrophilic-lipophilic balance of polymeric templates and concentration of iron cations on the magnetite formation were investigated along with the development of ferrogel preparation technique. Cytotoxicity, physical and chemical properties of obtained magnetic hydrogels have been studied in this work. Copyright © 2012 Elsevier B.V. All rights reserved.

Thermo-responsive cell culture carriers based on poly(vinyl methyl ether)—the effect of biomolecular ligands to balance cell adhesion and stimulated detachment

NASA Astrophysics Data System (ADS)

Teichmann, Juliane; Nitschke, Mirko; Pette, Dagmar; Valtink, Monika; Gramm, Stefan; Härtel, Frauke V.; Noll, Thomas; Funk, Richard H. W.; Engelmann, Katrin; Werner, Carsten

2015-08-01

Two established material systems for thermally stimulated detachment of adherent cells were combined in a cross-linked polymer blend to merge favorable properties. Through this approach poly(N-isopropylacrylamide) (PNiPAAm) with its superior switching characteristic was paired with a poly(vinyl methyl ether)-based composition that allows adjusting physico-chemical and biomolecular properties in a wide range. Beyond pure PNiPAAm, the proposed thermo-responsive coating provides thickness, stiffness and swelling behavior, as well as an apposite density of reactive sites for biomolecular functionalization, as effective tuning parameters to meet specific requirements of a particular cell type regarding initial adhesion and ease of detachment. To illustrate the strength of this approach, the novel cell culture carrier was applied to generate transplantable sheets of human corneal endothelial cells (HCEC). Sheets were grown, detached, and transferred onto planar targets. Cell morphology, viability and functionality were analyzed by immunocytochemistry and determination of transepithelial electrical resistance (TEER) before and after sheet detachment and transfer. HCEC layers showed regular morphology with appropriate TEER. Cells were positive for function-associated marker proteins ZO-1, Na+/K+-ATPase, and paxillin, and extracellular matrix proteins fibronectin, laminin and collagen type IV before and after transfer. Sheet detachment and transfer did not impair cell viability. Subsequently, a potential application in ophthalmology was demonstrated by transplantation onto de-endothelialized porcine corneas in vitro. The novel thermo-responsive cell culture carrier facilitates the generation and transfer of functional HCEC sheets. This paves the way to generate tissue engineered human corneal endothelium as an alternative transplant source for endothelial keratoplasty.

Thermo-responsive cell culture carriers based on poly(vinyl methyl ether)-the effect of biomolecular ligands to balance cell adhesion and stimulated detachment.

PubMed

Teichmann, Juliane; Nitschke, Mirko; Pette, Dagmar; Valtink, Monika; Gramm, Stefan; Härtel, Frauke V; Noll, Thomas; Funk, Richard H W; Engelmann, Katrin; Werner, Carsten

2015-08-01

Two established material systems for thermally stimulated detachment of adherent cells were combined in a cross-linked polymer blend to merge favorable properties. Through this approach poly( N -isopropylacrylamide) (PNiPAAm) with its superior switching characteristic was paired with a poly(vinyl methyl ether)-based composition that allows adjusting physico-chemical and biomolecular properties in a wide range. Beyond pure PNiPAAm, the proposed thermo-responsive coating provides thickness, stiffness and swelling behavior, as well as an apposite density of reactive sites for biomolecular functionalization, as effective tuning parameters to meet specific requirements of a particular cell type regarding initial adhesion and ease of detachment. To illustrate the strength of this approach, the novel cell culture carrier was applied to generate transplantable sheets of human corneal endothelial cells (HCEC). Sheets were grown, detached, and transferred onto planar targets. Cell morphology, viability and functionality were analyzed by immunocytochemistry and determination of transepithelial electrical resistance (TEER) before and after sheet detachment and transfer. HCEC layers showed regular morphology with appropriate TEER. Cells were positive for function-associated marker proteins ZO-1, Na + /K + -ATPase, and paxillin, and extracellular matrix proteins fibronectin, laminin and collagen type IV before and after transfer. Sheet detachment and transfer did not impair cell viability. Subsequently, a potential application in ophthalmology was demonstrated by transplantation onto de-endothelialized porcine corneas in vitro . The novel thermo-responsive cell culture carrier facilitates the generation and transfer of functional HCEC sheets. This paves the way to generate tissue engineered human corneal endothelium as an alternative transplant source for endothelial keratoplasty.

Thermo-responsive cell culture carriers based on poly(vinyl methyl ether)—the effect of biomolecular ligands to balance cell adhesion and stimulated detachment

PubMed Central

Teichmann, Juliane; Nitschke, Mirko; Pette, Dagmar; Valtink, Monika; Gramm, Stefan; Härtel, Frauke V; Noll, Thomas; Funk, Richard H W; Engelmann, Katrin; Werner, Carsten

2015-01-01

Two established material systems for thermally stimulated detachment of adherent cells were combined in a cross-linked polymer blend to merge favorable properties. Through this approach poly(N-isopropylacrylamide) (PNiPAAm) with its superior switching characteristic was paired with a poly(vinyl methyl ether)-based composition that allows adjusting physico-chemical and biomolecular properties in a wide range. Beyond pure PNiPAAm, the proposed thermo-responsive coating provides thickness, stiffness and swelling behavior, as well as an apposite density of reactive sites for biomolecular functionalization, as effective tuning parameters to meet specific requirements of a particular cell type regarding initial adhesion and ease of detachment. To illustrate the strength of this approach, the novel cell culture carrier was applied to generate transplantable sheets of human corneal endothelial cells (HCEC). Sheets were grown, detached, and transferred onto planar targets. Cell morphology, viability and functionality were analyzed by immunocytochemistry and determination of transepithelial electrical resistance (TEER) before and after sheet detachment and transfer. HCEC layers showed regular morphology with appropriate TEER. Cells were positive for function-associated marker proteins ZO-1, Na+/K+-ATPase, and paxillin, and extracellular matrix proteins fibronectin, laminin and collagen type IV before and after transfer. Sheet detachment and transfer did not impair cell viability. Subsequently, a potential application in ophthalmology was demonstrated by transplantation onto de-endothelialized porcine corneas in vitro. The novel thermo-responsive cell culture carrier facilitates the generation and transfer of functional HCEC sheets. This paves the way to generate tissue engineered human corneal endothelium as an alternative transplant source for endothelial keratoplasty. PMID:27877823

Polymer grafted magnetic nanoparticles for delivery of anticancer drug at lower pH and elevated temperature.

PubMed

Dutta, Sujan; Parida, Sheetal; Maiti, Chiranjit; Banerjee, Rakesh; Mandal, Mahitosh; Dhara, Dibakar

2016-04-01

Efficient and controlled delivery of therapeutics to tumor cells is one of the important issues in cancer therapy. In the present work, a series of pH- and temperature-responsive polymer grafted iron oxide nanoparticles were prepared by simple coupling of aminated iron oxide nanoparticle with poly(N-isopropylacrylamide-ran-poly(ethylene glycol) methyl ether acrylate)-block-poly(acrylic acid) (P(NIPA-r-PEGMEA)-b-PAA). For this, three water soluble block polymers were prepared via reversible addition fragmentation transfer (RAFT) polymerization technique. At first, three different block copolymers were prepared by polymerizing mixture of NIPA and PEGMEA (with varying mole ratio) in presence of poly(tert-butyl acrylate) (PtBA) macro chain transfer agent. Subsequently, P(NIPA-r-PEGMEA)-b-PAA copolymers were synthesized by hydrolyzing tert-butyl acrylate groups of the P(NIPA-r-PEGMEA)-b-PtBA copolymers. The resulting polymers were then grafted to iron oxide nanoparticles, and these functionalized nanoparticles were thoroughly characterized by X-ray diffraction (XRD), thermogravimetric analysis (TGA), zeta potential measurements, transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), vibrating sample magnetometer (VSM) and Fourier transform infrared spectroscopy (FTIR). Doxorubicin (DOX), an anti-cancer drug, was loaded into the polymer coated nanoparticles and its release behavior was subsequently studied at different pH and temperatures. The drug release pattern revealed a sustained release of DOX preferentially at the desired lysosomal pH of cancer cells (pH 5.0) and slightly above the physiological temperature depending upon the composition of the copolymers. The potential anticancer activity of the polymer grafted DOX loaded nanoparticles were established by MTT assay and apoptosis study of cervical cancer ME 180cells in presence of the nanoparticles. Thus, these particles can be utilized for controlled delivery of anticancer drugs at the desired lysosomal pH and/or by slightly heating the cells using magnetic hyperthermia. Copyright © 2016 Elsevier Inc. All rights reserved.

Poly(NIPAm-AMPS) nanoparticles for targeted delivery of anti-inflammatory cell penetrating peptides

NASA Astrophysics Data System (ADS)

Bartlett, Rush Lloyd, II

Inflammatory diseases such as osteoarthritis and rheumatoid arthritis cause $127.8 billion in US healthcare expenditures each year and are the cause of disability for 27% of disabled persons in the United States. Current treatment options rarely halt disease progression and often result in significant unwanted and debilitating side effects. Our laboratory has previously developed a family of cell penetrating peptides (CPPs) which inhibit the activity of mitogen activated protein kinase activate protein kinase 2 (MK2). MK2 mediates the inflammatory response by activating Tristetraprline (TTP). Once activated, TTP rapidly stabilizes AU rich regions of pro-inflammatory cytokine mRNA which allows translation of pro-inflammatory cytokines to occur. Blocking MK2 with our labs CPPs yields a decrease in inflammatory activity but CPPs by are highly non specific and prone to rapid enzymatic degradation in vivo.. In order to increase the potency of MK2 inhibiting CPPs we have developed a novel nanoparticle drug carrier composed of poly(N-isopropylacrylamide-co-2-acrylamido-2-methyl-1-propanesulfonic acid). This drug carrier has been shown to have preliminary efficacy in vitro and ex vivo for suppressing pro-inflammatory cytokine production when releasing CPPs. This thesis will present progress made on three aims: Specific Aim 1) Create and validate a NIPAm based drug delivery system that mimics the binding and release previously observed between cell penetrating peptides and glycosaminoglycans. Specific Aim 2) Engineer degradability into poly(NIPAm-AMPS) nanoparticles to enable more drug to be released and qualify that system in vitro. Specific Aim 3) Validate poly(NIPAm-AMPS) nanoparticles for targeted drug delivery in an ex vivo inflammatory model. Overall we have developed a novel anionic nanoparticle system that is biocompatible and efficient at loading and releasing cell penetrating peptides to inflamed tissue. Once loaded with a CPP the nanoparticle drug complex is capable of targeting diseased tissue and preventing the production of pro-inflammatory cytokines in both in vitro and ex vivo models.

Phenotype of hepatocyte spheroids in Arg-GLY-Asp (RGD) containing a thermo-reversible extracellular matrix.

PubMed

Park, Keun-Hong; Bae, You Han

2002-07-01

The spheroid of specific cells is often regarded as the better form in artificial organs and mammalian cell bioreactors for improved cell-specific functions. In this study, freshly harvested primary rat hepatocytes, which had been cultivated as spheroids and entrapped in a synthetic thermo-reversible extracellular matrix, were examined for differentiated morphology and enhanced liver-specific functions as compared to a control set (hepatocytes in single-cell form). A copolymer of N-isopropylacrylamide (98 mole % in the feed) and acrylic acid (poly(NiPAAm-co-AAc)), and the adhesion molecule, an Arg-Gly-Asp (RGD)-incorporated thermo-reversible matrix, were used to entrap hepatocytes in the form of either spheroids or single cells. In a 28-day culture period, the spheroids in the RGD-incorporated gel maintained higher viability and produced albumin and urea at constant rates, while there was lower cell viability and less albumin secretion by the spheroids in p(NiPAAm-co-AAc). Hepatocytes cultured as spheroids in the RGD-incorporated gel would constitute a potentially useful three-dimensional cell system for application in a bio-artificial liver device.

Responsive copolymer–graphene oxide hybrid microspheres with enhanced drug release properties

DOE PAGES

Dong, Fuping; Firkowska-Boden, Izabela; Arras, Matthias M. L.; ...

2017-01-13

Here, the ability to integrate both high encapsulation efficiency and controlled release in a drug delivery system (DDS) is a highly sought solution to cure major diseases. However, creation of such a system is challenging. This study was aimed at constructing a new delivery system based on thermoresponsive poly(N-isopropylacrylamide-co-styrene) (PNIPAAm-co-PS) hollow microspheres prepared via two-step precipitation polymerization. To control the diffusion-driven drug release, the PNIPAAm-co-PS spheres were electrostatically coated with graphene oxide (GO) nanosheets. As a result of the coating the permeability of such copolymer-GO hybrid microspheres was reduced to the extent that suppressed the initial burst release and enabledmore » sustained drug release in in vitro testing. The hybrid microspheres showed improved drug encapsulation by 46.4% which was attributed to the diffusion barrier properties and -conjugated structure of GO. The system presented here is promising to advance, e.g., the anticancer drug delivery technologies by enabling sustained drug release and thus minimizing local and systemic side effects.« less

Adsorption behavior of proteins on temperature-responsive resins.

PubMed

Poplewska, Izabela; Muca, Renata; Strachota, Adam; Piątkowski, Wojciech; Antos, Dorota

2014-01-10

The adsorption behavior of proteins on thermo-responsible resins based on poly(N-isopropylacrylamide) and its copolymer containing an anionic co-monomer has been investigated. The influence of the polymer composition, i.e., the content of the co-monomer and crosslinker on the thermo-sensitivity of the protein adsorption has been quantified. The properties of ungrafted polymer as well grafted onto the agarose matrix have been analyzed and compared. Batch and dynamic (column) experiments have been performed to measure the adsorption equilibrium of proteins and to quantify the phase transition process. As model proteins lysozyme, lactoferrin, α-chymotrypsinogen A and ovalbumin have been used. The adsorption process was found to be governed by ionic interactions between the negatively charged surface of resin and the protein, which enabled separation of proteins differing in electrostatic charge. The interactions enhanced with increase of temperature. Decrease of temperature facilitated desorption of proteins and reduced the salt usage in the desorption buffer. Grafted polymers exhibited markedly higher mechanical stability and, however, weaker temperature response compared to the ungrafted ones. Copyright © 2013 Elsevier B.V. All rights reserved.

Hollow microgels squeezed in overcrowded environments

NASA Astrophysics Data System (ADS)

Scotti, A.; Brugnoni, M.; Rudov, A. A.; Houston, J. E.; Potemkin, I. I.; Richtering, W.

2018-05-01

We study how a cavity changes the response of hollow microgels with respect to regular ones in overcrowded environments. The structural changes of hollow poly(N-isopropylacrylamide) microgels embedded within a matrix of regular ones are probed by small-angle neutron scattering with contrast variation. The form factors of the microgels at increasing compressions are directly measured. The decrease of the cavity size with increasing concentration shows that the hollow microgels have an alternative way with respect to regular cross-linked ones to respond to the squeezing due to their neighbors. The structural changes under compression are supported by the radial density profiles obtained with computer simulations. The presence of the cavity offers to the polymer network the possibility to expand toward the center of the microgels in response to the overcrowded environment. Furthermore, upon increasing compression, a two step transition occurs: First the microgels are compressed but the internal structure is unchanged; then, further compression causes the fuzzy shell to collapse completely and reduce the size of the cavity. Computer simulations also allow studying higher compression degrees than in the experiments leading to the microgel's faceting.

Responsive copolymer–graphene oxide hybrid microspheres with enhanced drug release properties

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

Dong, Fuping; Firkowska-Boden, Izabela; Arras, Matthias M. L.

Here, the ability to integrate both high encapsulation efficiency and controlled release in a drug delivery system (DDS) is a highly sought solution to cure major diseases. However, creation of such a system is challenging. This study was aimed at constructing a new delivery system based on thermoresponsive poly(N-isopropylacrylamide-co-styrene) (PNIPAAm-co-PS) hollow microspheres prepared via two-step precipitation polymerization. To control the diffusion-driven drug release, the PNIPAAm-co-PS spheres were electrostatically coated with graphene oxide (GO) nanosheets. As a result of the coating the permeability of such copolymer-GO hybrid microspheres was reduced to the extent that suppressed the initial burst release and enabledmore » sustained drug release in in vitro testing. The hybrid microspheres showed improved drug encapsulation by 46.4% which was attributed to the diffusion barrier properties and -conjugated structure of GO. The system presented here is promising to advance, e.g., the anticancer drug delivery technologies by enabling sustained drug release and thus minimizing local and systemic side effects.« less

Light responsive hybrid nanofibres for on-demand therapeutic drug and cell delivery.

PubMed

Li, Yan-Fang; Slemming-Adamsen, Peter; Wang, Jing; Song, Jie; Wang, Xueqin; Yu, Ying; Dong, Mingdong; Chen, Chunying; Besenbacher, Flemming; Chen, Menglin

2017-08-01

Smart materials for on-demand delivery of therapeutically active agents are challenging in pharmaceutical and biomaterials science. In the present study, we report hybrid nanofibres capable of being reversibly controlled to pulsatile deliver both therapeutic drugs and cells on-demand of near-infrared (NIR) light. The nanofibres, fabricated by co-electrospinning of poly (N-isopropylacrylamide), silica-coated gold nanorods and polyhedral oligomeric silsesquinoxanes have, for the first time, demonstrated rapid, reversible large-volume changes of 83% on-demand with NIR stimulation, with retained nanofibrous morphology. Combining with the extracellular matrix-mimicking fibrillary properties, the nanofibres achieved accelerated release of model drug or cells on demand with NIR triggering. The release of the model drug doxorubicin demonstrated normal anti-cancer efficacy by reducing the viability of human cervical cancer HeLa cells by 97% in 48 h. In parallel, the fibres allowed model cell NIH3T3 fibroblast entrapment, adhesion, proliferation, differentiation and, upon NIR irradiation, cell release with undisturbed cellular function. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A smart core-sheath nanofiber that captures and releases red blood cells from the blood.

PubMed

Shi, Q; Hou, J; Zhao, C; Xin, Z; Jin, J; Li, C; Wong, S-C; Yin, J

2016-01-28

A smart core-sheath nanofiber for non-adherent cell capture and release is demonstrated. The nanofibers are fabricated by single-spinneret electrospinning of poly(N-isopropylacrylamide) (PNIPAAm), polycaprolactone (PCL) and nattokinase (NK) solution blends. The self-assembly of PNIPAAm and PCL blends during the electrospinning generates the core-sheath PCL/PNIPAAm nanofibers with PNIPAAm as the sheath. The PNIPAAm-based core-sheath nanofibers are switchable between hydrophobicity and hydrophilicity with temperature change and enhance stability in the blood. When the nanofibers come in contact with blood, the NK is released from the nanofibers to resist platelet adhesion on the nanofiber surface, facilitating the direct capture and isolation of red blood cells (RBCs) from the blood above phase-transition temperature of PNIPAAm. Meanwhile, the captured RBCs are readily released from the nanofibers with temperature stimuli in an undamaged manner. The release efficiency of up to 100% is obtained while maintaining cellular integrity and function. This work presents promising nanofibers to effectively capture non-adherent cells and release for subsequent molecular analysis and diagnosis of single cells.

Preparation and characterization of a thermoresponsive gigaporous medium for high-speed protein chromatography.

PubMed

Qu, Jian-Bo; Chen, Yan-Li; Huan, Guan-Sheng; Zhou, Wei-Qing; Liu, Jian-Guo; Zhu, Hu; Zhang, Xiao-Yun

2015-01-01

A high-speed thermoresponsive medium was developed by grafting poly(N-isopropylacrylamide-co-butyl methacrylate) (P(NIPAM-co-BMA)) brushes onto gigaporous polystyrene (PS) microspheres via surface-initiated atom transfer radical polymerization (ATRP) technique, which has strong mechanical strength, good chemical stability and high mass transfer rate for biomacromolecules. The gigaporous structure, surface chemical composition, static protein adsorption, and thermoresponsive chromatographic properties of prepared medium (PS-P(NIPAM-co-BMA)) were characterized in detail. Results showed that the PS microspheres were successfully grafted with P(NIPAM-co-BMA) brushes and that the gigaporous structure was robustly maintained. After grafting, the nonspecific adsorption of proteins on PS microspheres was greatly reduced. A column packed with PS-P(NIPAM-co-BMA) exhibited low backpressure and significant thermo-responsibility. By simply changing the column temperature, it was able to separate three model proteins at the mobile phase velocity up to 2167 cm h(-1). In conclusion, the thermoresponsive polymer brushes grafted gigaporous PS microspheres prepared by ATRP are very promising in 'green' high-speed preparative protein chromatography. Copyright © 2014 Elsevier B.V. All rights reserved.

Charge segregation in weakly ionized microgels

DOE PAGES

Hyatt, John S.; Douglas, Alison M.; Stanley, Chris; ...

2017-01-19

Here we investigate microgels synthesized from N-isopropylacrylamide (NIPAM) copolymerized with a large mol% of acrylic acid, finding that when the acid groups are partially ionized at high temperatures, competition between ion-induced swelling and hydrophobic deswelling of poly(NIPAM) chains results in microphase separation. In cross-linked microgels, this manifests as a dramatic decrease in the ratio between the radius of gyration and the hydrodynamic radius to ~0.2, indicating that almost all the mass of the microgel is concentrated near the particle center. We also observe a concurrent decrease of the polymer network length scale via small-angle neutron scattering, confirming the presence ofmore » a dense, deswollen core surrounded by a diffuse, charged periphery. We compare these results to those obtained for a system of charged ultralow-cross-linked microgels; the form factor shows a distinct peak at high q when the temperature exceeds a threshold value. Lastly, we successfully fit the form factor to theory developed to describe scattering from weakly charged gels in poor solvents, and we tie this behavior to charge segregation in the case of the cross-linked microgels.« less

Ultrathin thermoresponsive self-folding 3D graphene

PubMed Central

Xu, Weinan; Qin, Zhao; Chen, Chun-Teh; Kwag, Hye Rin; Ma, Qinli; Sarkar, Anjishnu; Buehler, Markus J.; Gracias, David H.

2017-01-01

Graphene and other two-dimensional materials have unique physical and chemical properties of broad relevance. It has been suggested that the transformation of these atomically planar materials to three-dimensional (3D) geometries by bending, wrinkling, or folding could significantly alter their properties and lead to novel structures and devices with compact form factors, but strategies to enable this shape change remain limited. We report a benign thermally responsive method to fold and unfold monolayer graphene into predesigned, ordered 3D structures. The methodology involves the surface functionalization of monolayer graphene using ultrathin noncovalently bonded mussel-inspired polydopamine and thermoresponsive poly(N-isopropylacrylamide) brushes. The functionalized graphene is micropatterned and self-folds into ordered 3D structures with reversible deformation under a full control by temperature. The structures are characterized using spectroscopy and microscopy, and self-folding is rationalized using a multiscale molecular dynamics model. Our work demonstrates the potential to design and fabricate ordered 3D graphene structures with predictable shape and dynamics. We highlight applicability by encapsulating live cells and creating nonlinear resistor and creased transistor devices. PMID:28989963

Superporous thermo-responsive hydrogels by combination of cellulose fibers and aligned micropores.

PubMed

Halake, Kantappa S; Lee, Jonghwi

2014-05-25

In the area of artificial hydrogels, simultaneous engineering of the volume transition characteristics and mechanical properties of stimuli-responsive hydrogels is an important subject. By unrestricted architecting of hierarchical structures, natural hydrogels are able to provide a wide range of swelling and mechanical properties, beyond the limits of artificial hydrogels. Herein, a combination of nanostructures and microstructures was developed to construct superporous hydrogels. Fibers of microfibrillated cellulose (MFC), an eco-friendly reinforcing material, were used as nanostructures, aligned micropores were used as microstructures, and in situ photopolymerization was used to immobilize the two structures together within the gel networks of poly(N-isopropyl acrylamide) (PNIPAm). The introduction of MFC distinctly enhanced volume transition, mainly by decreasing the swelling ratios above the transition. The introduction of directional micropores increased the swelling ratio below the transition and decreased the swelling ratio above the transition, thereby also enhancing the volume transition. Additionally, the formation of aligned micropores achieved fast water infiltration, which is beneficial for superabsorbent applications. The introduction of aligned micropores reduced the elastic modulus, but this could partially be compensated for by reinforcement with MFC. This combination of crystalline nanofibers and aligned micropores has great potential for the development of stimuli-responsive superporous hydrogels outperforming current artificial hydrogels. Copyright © 2014 Elsevier Ltd. All rights reserved.

A Facile Strategy for Catalyst Separation and Recycling Suitable for ATRP of Hydrophilic Monomers Using a Macroligand.

PubMed

Jiang, Xiaowu; Wu, Jian; Zhang, Lifen; Cheng, Zhenping; Zhu, Xiulin

2016-01-01

How to simply and efficiently separate and recycle catalyst has still been a constraint for the wide application of atom transfer radical polymerization (ATRP), especially for the polymerization systems with hydrophilic monomers because the polar functional groups may coordinate with transition metal salts, resulting in abundant catalyst residual in the resultant water-soluble polymers. In order to overcome this problem, a latent-biphasic system is developed, which can be successfully used for ATRP catalyst separation and recycling in situ for various kinds of hydrophilic monomers for the first time, such as poly(ethylene glycol) monomethyl ether methacrylate (PEGMA), 2-hydroxyethyl methacrylate (HEMA), 2-(dimethylamino)ethyl methacrylate (DMAEMA), N,N-dimethyl acrylamide (DMA), and N-isopropylacrylamide (NIPAM). Herein, random copolymer of octadecyl acrylate (OA), MA-Ln (2-(bis(pyridin-2-ylmethyl)amino)ethyl acrylate), and POA-ran-P(MA-Ln) is designed as the macroligand, and heptane/ethanol is selected as the biphasic solvent. Copper(II) bromide (CuBr2 ) is employed as the catalyst, PEG-bound 2-bromo-2-methylpropanoate (PEG350 -Br) as the water-soluble ATRP initiator and 2,2'-azobis(isobutyronitrile) (AIBN) as the azo-initiator to establish an ICAR (initiators for continuous activator regeneration) ATRP system. Importantly, well-defined water-soluble polymers are obtained even though the recyclable catalyst is used for sixth times. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Stimuli-Responsive DNA-Based Hydrogels: From Basic Principles to Applications.

PubMed

Kahn, Jason S; Hu, Yuwei; Willner, Itamar

2017-04-18

The base sequence of nucleic acids encodes structural and functional information into the DNA biopolymer. External stimuli such as metal ions, pH, light, or added nucleic acid fuel strands provide triggers to reversibly switch nucleic acid structures such as metal-ion-bridged duplexes, i-motifs, triplex nucleic acids, G-quadruplexes, or programmed double-stranded hybrids of oligonucleotides (DNA). The signal-triggered oligonucleotide structures have been broadly applied to develop switchable DNA nanostructures and DNA machines, and these stimuli-responsive assemblies provide functional scaffolds for the rapidly developing area of DNA nanotechnology. Stimuli-responsive hydrogels undergoing signal-triggered hydrogel-to-solution transitions or signal-controlled stiffness changes attract substantial interest as functional matrices for controlled drug delivery, materials exhibiting switchable mechanical properties, acting as valves or actuators, and "smart" materials for sensing and information processing. The integration of stimuli-responsive oligonucleotides with hydrogel-forming polymers provides versatile means to exploit the functional information encoded in the nucleic acid sequences to yield stimuli-responsive hydrogels exhibiting switchable physical, structural, and chemical properties. Stimuli-responsive DNA-based nucleic acid structures are integrated in acrylamide polymer chains and reversible, switchable hydrogel-to-solution transitions of the systems are demonstrated by applying external triggers, such as metal ions, pH-responsive strands, G-quadruplex, and appropriate counter triggers that bridge and dissociate the polymer chains. By combining stimuli-responsive nucleic acid bridges with thermosensitive poly(N-isopropylacrylamide) (pNIPAM) chains, systems undergoing reversible solution ↔ hydrogel ↔ solid transitions are demonstrated. Specifically, by bridging acrylamide polymer chains by two nucleic acid functionalities, where one type of bridging unit provides a stimuli-responsive element and the second unit acts as internal "bridging memory", shape-memory hydrogels undergoing reversible and switchable transitions between shaped hydrogels and shapeless quasi-liquid states are demonstrated. By using stimuli-responsive hydrogel cross-linking units that can assemble the bridging units by two different input signals, the orthogonally-triggered functions of the shape-memory were shown. Furthermore, a versatile approach to assemble stimuli-responsive DNA-based acrylamide hydrogel films on surfaces is presented. The method involves the activation of the hybridization chain-reaction (HCR) by a surface-confined promoter strand, in the presence of acrylamide chains modified with two DNA hairpin structures and appropriate stimuli-responsive tethers. The resulting hydrogel-modified surfaces revealed switchable stiffness properties and signal-triggered catalytic functions. By applying the method to assemble the hydrogel microparticles, substrate-loaded, stimuli-responsive microcapsules are prepared. The signal-triggered DNA-based hydrogel microcapsules are applied as drug carriers for controlled release. The different potential applications and future perspectives of stimuli responsive hydrogels are discussed. Specifically, the use of these smart materials and assemblies as carriers for controlled drug release and as shape-memory matrices for information storage and inscription and the use of surface-confined stimuli-responsive hydrogels, exhibiting switchable stiffness properties, for catalysis and controlled growth of cells are discussed.

Comment on "Relating side chain organization of PNIPAm with its conformation in aqueous methanol" by D. Mukherji, M. Wagner, M. D. Watson, S. Winzen, T. E. de Oliveira, C. M. Marques and K. Kremer, Soft Matter, 2016, 12, 7995.

PubMed

Pica, Andrea; Graziano, Giuseppe

2017-11-01

In a recent article, Kremer and co-workers have combined NMR measurements and very long, all-atom MD simulations to strengthen their original claim that PNIPAM cononsolvency in water-methanol solutions is driven by the ability of MeOH molecules to bridge different monomers far away along the polymeric chain. In this comment, the results presented by Kremer and co-workers are reviewed, analyzed, and questioned regarding their ability to provide support to the bridging mechanism. Here, some pieces of evidence are provided to show that: (1) the solvent-excluded volume effect plays always a fundamental role in polymer collapse; (2) PNIPAM cononsolvency is caused by the geometric-energetic frustration experienced by the polymer when it can interact with both water and methanol molecules at the same time.

Multifunctional particles for melanoma-targeted drug delivery.

PubMed

Wadajkar, Aniket S; Bhavsar, Zarna; Ko, Cheng-Yu; Koppolu, Bhanuprasanth; Cui, Weina; Tang, Liping; Nguyen, Kytai T

2012-08-01

New magnetic-based core-shell particles (MBCSPs) were developed to target skin cancer cells while delivering chemotherapeutic drugs in a controlled fashion. MBCSPs consist of a thermo-responsive shell of poly(N-isopropylacrylamide-acrylamide-allylamine) and a core of poly(lactic-co-glycolic acid) (PLGA) embedded with magnetite nanoparticles. To target melanoma cancer cells, MBCSPs were conjugated with Gly-Arg-Gly-Asp-Ser (GRGDS) peptides that specifically bind to the α(5)β(3) receptors of melanoma cells. MBCSPs consist of unique multifunctional and controlled drug delivery characteristics. Specially, they can provide dual drug release mechanisms (a sustained release of drugs through degradation of PLGA core and a controlled release in response to changes in temperature via thermo-responsive polymer shell), and dual targeting mechanisms (magnetic localization and receptor-mediated targeting). Results from in vitro studies indicate that GRGDS-conjugated MBCSPs have an average diameter of 296 nm and exhibit no cytotoxicity towards human dermal fibroblasts up to 500 μg ml(-1). Further, a sustained release of curcumin from the core and a temperature-dependent release of doxorubicin from the shell of MBCSPs were observed. The particles also produced a dark contrast signal in magnetic resonance imaging. Finally, the particles were accumulated at the tumor site in a B16F10 melanoma orthotopic mouse model, especially in the presence of a magnet. Results indicate great potential of MBCSPs as a platform technology to target, treat and monitor melanoma for targeted drug delivery to reduce side effects of chemotherapeutic reagents. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Characterization of Phenotypic and Transcriptional Differences in Human Pluripotent Stem Cells under 2D and 3D Culture Conditions.

PubMed

Kamei, Ken-Ichiro; Koyama, Yoshie; Tokunaga, Yumie; Mashimo, Yasumasa; Yoshioka, Momoko; Fockenberg, Christopher; Mosbergen, Rowland; Korn, Othmar; Wells, Christine; Chen, Yong

2016-11-01

Human pluripotent stem cells hold great promise for applications in drug discovery and regenerative medicine. Microfluidic technology is a promising approach for creating artificial microenvironments; however, although a proper 3D microenvironment is required to achieve robust control of cellular phenotypes, most current microfluidic devices provide only 2D cell culture and do not allow tuning of physical and chemical environmental cues simultaneously. Here, the authors report a 3D cellular microenvironment plate (3D-CEP), which consists of a microfluidic device filled with thermoresponsive poly(N-isopropylacrylamide)-β-poly(ethylene glycol) hydrogel (HG), which enables systematic tuning of both chemical and physical environmental cues as well as in situ cell monitoring. The authors show that H9 human embryonic stem cells (hESCs) and 253G1 human induced pluripotent stem cells in the HG/3D-CEP system maintain their pluripotent marker expression under HG/3D-CEP self-renewing conditions. Additionally, global gene expression analyses are used to elucidate small variations among different test environments. Interestingly, the authors find that treatment of H9 hESCs under HG/3D-CEP self-renewing conditions results in initiation of entry into the neural differentiation process by induction of PAX3 and OTX1 expression. The authors believe that this HG/3D-CEP system will serve as a versatile platform for developing targeted functional cell lines and facilitate advances in drug screening and regenerative medicine. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Surface design of antibody-immobilized thermoresponsive cell culture dishes for recovering intact cells by low-temperature treatment.

PubMed

Kobayashi, Jun; Hayashi, Masaki; Ohno, Takahiro; Nishi, Masanori; Arisaka, Yoshinori; Matsubara, Yoshinori; Kakidachi, Hiroshi; Akiyama, Yoshikatsu; Yamato, Masayuki; Horii, Akihiro; Okano, Teruo

2014-11-01

Antibody-immobilized thermoresponsive poly(N-isopropylacrylamide-co-2-carboxyisopropylacrylamide) [poly(IPAAm-co-CIPAAm)]-grafted cell culture surfaces were designed to enhance both the initial adhesion of weakly adhering cells and the ability of cells to detach in response to low temperature through the regulation of affinity binding between immobilized antibodies and antigens on the cellular surface. Ty-82 cells and neonatal normal human dermal fibroblasts (NHDFs), which express CD90 on the cell surface, adhered to anti-CD90 antibody-immobilized thermoresponsive surfaces at 37°C, a condition at which the grafted thermoresponsive polymer chains shrank. Adherent Ty-82 cells were detached from the surfaces by lowering the temperature to 20°C and applying external forces, such as pipetting, whereas cultured NHDF sheets spontaneously detached themselves from the surface in response to reduced temperature alone. When the temperature was decreased to 20°C, the swelling of grafted thermoresponsive polymer chains weakened the affinity binding between immobilized antibody and antigen on the cells due to the increasing steric hindrance of the polymer chains around the antigen-recognition site of the immobilized antibodies. No contamination was detected on cells harvested from covalently immobilized antibodies on the culture surfaces by low-temperature treatment, whereas a carryover of the antibody and avidin from the avidin-biotin binding surface was observed. Furthermore, the initial adhesion of adipose tissue-derived cells, which adhere weakly to PIPAAm-grafted surfaces, was enhanced on the antibody-immobilized thermoresponsive surfaces. © 2013 Wiley Periodicals, Inc.

Composite Polymeric Membranes with Directionally Embedded Fibers for Controlled Dual Actuation.

PubMed

Liu, Li; Bakhshi, Hadi; Jiang, Shaohua; Schmalz, Holger; Agarwal, Seema

2018-04-20

In this paper, preparation method and actuation properties of an innovative composite membrane composed of thermo- and pH-responsive poly(N-isopropylacrylamide-co-acrylic acid) fibers (average diameter ≈ 905 nm) embedded within a passive thermoplastic polyurethane (TPU) matrix at different angles with degree of alignment as high as 98% are presented. The composite membrane has a gradient of TPU along the thickness. It has the capability of temperature- and pH-dependent direction-, and size-controlled actuation in few minutes. The stresses generated at the responsive fiber and nonresponsive matrix provide actuation, whereas the angle at which fibers are embedded in the matrix controls the actuation direction and size. The temperature has no effect on actuation and actuated forms at pH 7 and above, whereas the size of the actuated forms can be controlled by the temperature at lower pH. The membranes are strong enough to reversibly lift and release ≈426 times weight of their own mass (2.47 g metal ring is lifted by a 5.8 mg membrane). Soft actuators are of interest as smart scaffolds, robotics, catalysis, drug release, energy storage, electrodes, and metamaterials. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In vivo non-invasive optical imaging of temperature-sensitive co-polymeric nanohydrogel

NASA Astrophysics Data System (ADS)

Chen, Haiyan; Zhang, Jian; Qian, Zhiyu; Liu, Fei; Chen, Xinyang; Hu, Yuzhu; Gu, Yueqing

2008-05-01

Assessment of hyperthermia in pathological tissue is a promising strategy for earlier diagnosis of malignant tumors. In this study, temperature-sensitive co-polymeric nanohydrogel poly(N-isopropylacrylamide-co-acrylic acid) (PNIPA-co-AA) was successfully synthesized by the precipitation polymerization method. The diameters of nanohydrogels were controlled to be less than 100 nm. Also the lower critical solution temperature (LCST, 40 °C) was manipulated above physiological temperature after integration of near-infrared (NIR) organic dye (heptamethine cyanine dye, HMCD) within its interior cores. NIR laser light (765 nm), together with sensitive charge coupled device (CCD) cameras, were designed to construct an NIR imaging system. The dynamic behaviors of PNIPA-co-AA-HMCD composites in denuded mice with or without local hyperthermia treatment were real-time monitored by an NIR imager. The results showed that the PNIPA-co-AA-HMCD composites accumulated in the leg treated with local heating and diffused much slower than that in the other leg without heating. The results demonstrated that the temperature-responsive PNIPA-co-AA-HMCD composites combining with an NIR imaging system could be an effective temperature mapping technique, which provides a promising prospect for earlier tumor diagnosis and thermally related therapeutic assessment.

An Ultra-High Fluorescence Enhancement and High Throughput Assay for Revealing Expression and Internalization of Chemokine Receptor CXCR4.

PubMed

He, Hua; Wang, Xiaojuan; Cheng, Tiantian; Xia, Yongqing; Lao, Jun; Ge, Baosheng; Ren, Hao; Khan, Naseer Ullah; Huang, Fang

2016-04-18

Revealing chemokine receptor CXCR4 expression, distribution, and internalization levels in different cancers helps to evaluate cancer progression or prognosis and to set personalized treatment strategy. We here describe a sensitive and high-throughput immunoassay for determining CXCR4 expression and distribution in cancer cells. The assay is accessible to a wide range of users in an ordinary lab only by dip-coating poly(styrene-co-N-isopropylacrylamide) spheres on the glass substrate. The self- assembled spheres form three-dimensional photonic colloidal crystals which enhance the fluorescence of CF647 and Alexa Fluor 647 by a factor of up to 1000. CXCR4 in cells is detected by using the sandwich immunoassay, where the primary antibody recognizes CXCR4 and the secondary antibody is labeled with CF647. With the newly established assay, we quantified the total expression of CXCR4, its distribution on the cell membrane and cytoplasm, and revealed their internalization level upon SDF-1α activation in various cancer cells, even for those with extremely low expression level. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Limitations in interpretation of Quartz Crystal Microbalance (QCM) beyond the rigid (Sauerbrey) to viscoelastic (lossy) transition

NASA Astrophysics Data System (ADS)

Wiener, Clinton; Weiss, Robert; White, Christopher; Vogt, Bryan

2014-03-01

Since Sauerbrey's 1959 discovery of the mass-frequency relationship in quartz, the QCM has been utilized to probe deposited mass layers. The mass to frequency (imaginary component of the impedance) relationship breaks down when the added mass is not rigidly coupled to the sensor surface and viscous dissipation of the quartz occurs. This dissipation is important in the deposition of soft materials such as polymers or biological molecules. By using a viscoelastic model for frequency and dissipation; the mass, viscosity, and shear modulus can be accurately determined. Here, we demonstrate an additional breakdown in the coupling of the imaginary component of the impedance to the mass by simultaneous QCM-D and spectroscopic ellipsometry (SE) measurements by examination of the swelling behavior of thin physically crosslinked poly-n-isopropylacrylamide films. A film swollen beyond 3 times its dry thickness shows a frequency increase (mass loss) and dissipation increases (increasing lossy film character) on cooling, but SE results show increased swelling of the film. This behavior was found to be thickness invariant for dry thicknesses of 32 nm and greater. Modeling of this QCM-D data shows non-physical results. Scaling concepts associated with this high loss limit will be discussed.

A flexible thermoresponsive cell culture substrate for direct transfer of keratinocyte cell sheets.

PubMed

Praveen, Wulligundam; Madathil, Bernadette K; Sajin Raj, R S; Kumary, T V; Anil Kumar, P R

2017-10-25

Most cell sheet engineering systems require a support or carrier to handle the harvested cell sheets. In this study, polyethylene terephthalate-based overhead projection transparency sheets (OHPS) were subjected to surface hydrolysis by alkali treatment to increase pliability and hydrophilicity and enable poly(N-isopropylacrylamide-co-glycidylmethacrylate) copolymer (NGMA) coating to impart thermoresponsiveness. NGMA was applied on the modified OHPS by the technique of spin coating using an indigenously designed spin coater. The spin coating had the advantage of using low volumes of the polymer and a reduced coating time. The surface chemistry and thermoresponsive coating was analyzed by Fourier transform infrared spectroscopy and water contact angle. Human keratinocyte cells were cultured on the spin coated surface and scaffold-free cell sheets were successfully harvested by simple variation of temperature. These cell sheets were found to be viable, exhibited epithelial characteristic and cell-cell contact as confirmed by positive immunostaining for ZO-1. The integrity and morphology of the cell sheet was confirmed by stereomicroscopy and E-SEM. These results highlight the potential of the NGMA spin coated modified OHPS to serve as a thermoresponsive culture surface-cum-flexible transfer tool.

Novel pH- and temperature-responsive blend hydrogel microspheres of sodium alginate and PNIPAAm-g-GG for controlled release of isoniazid.

PubMed

Kajjari, Praveen B; Manjeshwar, Lata S; Aminabhavi, Tejraj M

2012-12-01

This paper reports the preparation and characterization of novel pH- and thermo-responsive blend hydrogel microspheres of sodium alginate (NaAlg) and poly(N-isopropylacrylamide)(PNIPAAm)-grafted-guar gum (GG) i.e., PNIPAAm-g-GG by emulsion cross-linking method using glutaraldehyde (GA) as a cross-linker. Isoniazid (INZ) was chosen as the model antituberculosis drug to achieve encapsulation up to 62%. INZ has a plasma half-life of 1.5 h, whose release was extended up to 12 h. Fourier transform infrared spectroscopy was used to confirm the grafting reaction and chemical stability of INZ during the encapsulation. Differential scanning calorimetry was used to investigate the drug's physical state, while powder X-ray diffraction confirmed the molecular level dispersion of INZ in the matrix. Scanning electron microscopy confirmed varying surface morphologies of the drug-loaded microspheres. Temperature- and pH-responsive nature of the blend hydrogel microspheres were investigated by equilibrium swelling, and in vitro release experiments were performed in pH 1.2 and pH 7.4 buffer media at 37°C as well as at 25°C. Kinetics of INZ release was analyzed by Ritger-Peppas empirical equation to compute the diffusional exponent parameter (n), whose value ranged between 0.27 and 0.58, indicating the release of INZ follows a diffusion swelling controlled release mechanism.

Stimuli-Responsive Reagent System for Enabling Microfluidic Immunoassays with Biomarker Purification and Enrichment

PubMed Central

2015-01-01

Immunoassays have been translated into microfluidic device formats, but significant challenges relating to upstream sample processing still limit their applications. Here, stimuli-responsive polymer–antibody conjugates are utilized in a microfluidic immunoassay to enable rapid biomarker purification and enrichment as well as sensitive detection. The conjugates were constructed by covalently grafting poly(N-isopropylacrylamide) (PNIPAAm), a thermally responsive polymer, to the lysine residues of anti-prostate specific antigen (PSA) Immunoglobulin G (IgG) using carbodiimide chemistry via the polymer end-carboxylate. The antibody-PNIPAAm (capture) conjugates and antibody-alkaline phosphatase (detection) conjugates formed sandwich immunocomplexes via PSA binding in 50% human plasma. The complexes were loaded into a recirculating poly(dimethylsiloxane) microreactor, equipped with micropumps and transverse flow features, for subsequent separation, enrichment, and quantification. The immunocomplexes were captured by heating the solution to 39 °C, mixed over the transverse features for 2 min, and washed with warm buffer. In one approach, the assay utilized immunocomplex solution that was contained in an 80 nL microreactor, which was loaded with solution at room temperature and subsequently heated to 39 °C. The assay took 25 min and resulted in 37 pM PSA limit of detection (LOD), which is comparable to a plate ELISA employing the same antibody pair. In another approach, the microreactor was preheated to 39 °C, and immunocomplex solution was flowed through the reactor, mixed, and washed. When the specimen volume was increased to 7.5 μL by repeating the capture process three times, the higher specimen volume led to immunocomplex enrichment within the microreactor. The resulting assay LOD was 0.5 pM, which is 2 orders of magnitude lower than the plate ELISA. Both approaches generate antigen specific signal over a clinically significant range. The sample processing capabilities and subsequent utility in a biomarker assay demonstrate the opportunity for stimuli-responsive polymer–protein conjugates in novel diagnostic technologies. PMID:25405605

Chemical and physical effects on the adhesion, maturation, and survival of monocytes, macrophages, and foreign body giant cells

NASA Astrophysics Data System (ADS)

Collier, Terry Odell, III

Injury caused by biomedical device implantation initiates inflammatory and wound healing responses. Cells migrate to the site of injury to degrade bacteria and toxins, create new vasculature, and form new and repair injured tissue. Blood-proteins rapidly adsorb onto the implanted material surface and express adhesive ligands which mediate cell adhesion on the material surface. Monocyte-derived macrophages and multi-nucleated foreign body giant cells adhere to the surface and degrade the surface of the material. Due to the role of macrophage and foreign body giant cell on material biocompatibility and biostability, the effects of surface chemistry, surface topography and specific proteins on the maturation and survival of monocytes, macrophages and foreign body giant cells has been investigated. Novel molecularly designed materials were used to elucidate the dynamic interactions which occur between inflammatory cells, proteins and surfaces. The effect of protein and protein adhesion was investigated using adhesive protein depleted serum conditions on RGD-modified and silane modified surfaces. The effects of surface chemistry were investigated using temperature responsive surfaces of poly (N-isopropylacrylamide) and micropatterned surfaces of N-(2 aminoethyl)-3-aminopropyltrimethoxysilane regions on an interpenetrating polymer network of polyacrylamide and poly(ethylene glycol). The physical effects were investigated using polyimide scaffold materials and polyurethane materials with surface modifying end groups. The depletion of immunoglobulin G caused decreased levels of macrophage adhesion, foreign body giant cell formation and increased levels of apoptosis. The temporal nature of macrophage adhesion was observed with changing effectiveness of adherent cell detachment with time, which correlated to increased expression of beta1 integrin receptors on detached macrophages with time. The limited ability of the micropatterned surface, polyimide scaffold and surface modified polyurethane materials to control macrophage adhesion indicates the complexity of macrophage adhesion and protein adsorption onto a surface. These studies have indicated components and adhesive mechanisms which can be utilized to create materials with enhanced resistance to macrophage adhesion and/or degradative abilities.

Thermosensitive nanospheres with a gold layer revealed as low-cytotoxic drug vehicles.

PubMed

Qin, Jian; Jo, Yun Suk; Ihm, Jong Eun; Kim, Do Kyung; Muhammed, Mamoun

2005-09-27

In this paper, the positive effect of a gold layer on cell viability is demonstrated by examining the results given by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfop henyl)-2H-tetrazolium (MTS) assay and two-color cell fluorescence viability (TCCV) assay. These cytotoxicity tests were performed with human cervical adenocarcinoma cells (HeLa cell line) and transformed African green monkey kidney fibroblast cells (Cos-7 cell line). To fabricate the nanostructures as drug vehicles, first, poly(l,l-lactide-co-ethylene glycol) (PLLA-PEG) and poly(N-isopropylacrylamide-co-D,D-lactide) (PNIPAAm-PDLA) were synthesized, and then two kinds of thermosensitive nanospheres comprising "shell-in-shell" structures without a gold layer (PLLA-PEG@PNIPAAm-PDLA) and with a gold layer (Au@PLLA-PEG@PNIPAAm-PDLA) were constructed by a modified double-emulsion method (MDEM). Both of them displayed a unique thermosensitive character exhibiting the lower critical solubility temperature (LCST) at 36.7 degrees C which was confirmed by UV-vis spectroscopy and differential scanning calorimetry (DSC). The release profiles of entrapped bovine serum albumin (BSA) were monitored at 22 and 37 degrees C, respectively, to reveal the thermal dependence on the release rate. In cell viability tests, both PLLA-PEG@PNIPAAm-PDLA and Au@PLLA-PEG@PNIPAAm-PDLA showed excellent cell viability, and furthermore, Au@PLLA-PEG@PNIPAAm-PDLA, particularly at high doses, exhibited more enhanced cell viability than PLLA-PEG@PNIPAAm-PDLA. This effect is mainly attributed to the gold layer which binds the protein molecules first and consequently facilitates transmembrane uptake of essential nutrients in the cell media, resulting in favorable cell proliferation.

In Vivo Efficacy of an Injectable Microsphere-Hydrogel Ocular Drug Delivery System.

PubMed

Osswald, Christian R; Guthrie, Micah J; Avila, Abigail; Valio, Joseph A; Mieler, William F; Kang-Mieler, Jennifer J

2017-09-01

Demonstrate in vivo that controlled and extended release of a low dose of anti-vascular endothelial growth factor (anti-VEGF) from a microsphere-hydrogel drug delivery system (DDS) has a therapeutic effect in a laser-induced rat model of choroidal neovascularization (CNV). Anti-VEGF (ranibizumab or aflibercept) was loaded into poly(lactic-co-glycolic acid) microspheres that were then suspended within an injectable poly(N-isopropylacrylamide)-based thermo-responsive hydrogel DDS.The DDS was shown previously to release bioactive anti-VEGF for ~200 days. CNV was induced using an Ar-green laser. The four experimental groups were as follows: (i) non-treated, (ii) drug-free DDS, (iii) anti-VEGF-loaded DDS, and (iv) bolus injection of anti-VEGF. CNV lesion areas were measured based on fluorescein angiograms and quantified using a multi-Otsu thresholding technique. Intraocular pressure (IOP) and dark-adapted electroretinogram (ERG) were also obtained pre- and post-treatment (1, 2, 4, 8, and 12 weeks). The anti-VEGF-loaded DDS group had significantly smaller (60%) CNV lesion areas than non-treated animals throughout the study. A small transient increase in IOP was seen immediately after injection; however, all IOP measurements at all time points were within the normal range. There were no significant changes in ERG maximal response compared to pre-treatment measurements for the drug-loaded DDS, which suggests no adverse effects on retinal cellular function. The current study demonstrates that the DDS can effectively decrease laser-induced CNV lesions in a murine model. Controlled and extended release from our DDS achieved greater treatment efficacy using an order of magnitude less drug than what is required with bolus administration. This suggests that our DDS may provide a significant advantage in the treatment of posterior segment eye diseases.

A Helical Flow, Circular Microreactor For Separating and Enriching “Smart” Polymer-Antibody Capture Reagents

PubMed Central

Hoffman, John M.; Ebara, Mitsuhiro; Lai, James J.; Hoffman, Allan S.; Folch, Albert

2011-01-01

We report a mechanistic study of how flow and recirculation in a microreactor can be used to optimize the capture and release of stimuli-responsive polymer-protein reagents on stimuli-responsive polymer-grafted channel surfaces. Poly(N-isopropylacrylamide) (PNIPAAm) was grafted to poly(dimethyl)siloxane (PDMS) channel walls, creating switchable surfaces where PNIPAAm-protein conjugates would adhere at temperatures above the lower critical solution temperature (LCST) and released below the LCST. A PNIPAAm-streptavidin conjugate that can capture biotinylated antibody-antigen targets was first characterized. The conjugate’s immobilization and release were limited by mass transport to and from the functionalized PNIPAAm surface. Transport and adsorption efficiencies were dependent on the aggregate size of the PNIPAAm-streptavidin conjugate above the LCST and also was dependent on whether the conjugates were heated in the presence of the stimuli-responsive surface or pre-aggregated and then flowed across the surface. As conjugate size increased, through the addition of non-conjugated PNIPAAm, recirculation and mixing were shown to markedly improve conjugate immobilization compared to diffusion alone. Under optimized conditions of flow and reagent concentrations, approximately 60% of a streptavidin conjugate bolus could be captured at the surface and subsequently successfully released. The kinetic release profile sharpness was also strongly improved with recirculation and helical mixing. Finally, the concentration of protein-polymer conjugates could be achieved by continuous conjugate flow into the heated recirculator, allowing nearly linear enrichment of the conjugate reagent from larger volumes. This capability was shown with anti-p24 HIV monoclonal antibody reagents that were enriched over 5-fold using this protocol. These studies provide insight into the mechanism of smart polymer-protein conjugate capture and release in grafted channels and show the potential of this purification and enrichment module for processing diagnostic samples. PMID:20882219

Superparamagnetic hollow hybrid nanogels as a potential guidable vehicle system of stimuli-mediated MR imaging and multiple cancer therapeutics.

PubMed

Chiang, Wen-Hsuan; Ho, Viet Thang; Chen, Hsin-Hung; Huang, Wen-Chia; Huang, Yi-Fong; Lin, Sung-Chyr; Chern, Chorng-Shyan; Chiu, Hsin-Cheng

2013-05-28

Hollow hybrid nanogels were prepared first by the coassembly of the citric acid-coated superparamagnetic iron oxide nanoparticles (SPIONs, 44 wt %) with the graft copolymer (56 wt %) comprising acrylic acid and 2-methacryloylethyl acrylate units as the backbone and poly(ethylene glycol) and poly(N-isopropylacrylamide) as the grafts in the aqueous phase of pH 3.0 in the hybrid vesicle structure, followed by in situ covalent stabilization via the photoinitiated polymerization of MEA residues within vesicles. The resultant hollow nanogels, though slightly swollen, satisfactorily retain their structural integrity while the medium pH is adjusted to 7.4. Confining SPION clusters to such a high level (44 wt %) within the pH-responsive thin gel layer remarkably enhances the transverse relaxivity (r2) and renders the MR imaging highly pH-tunable. For example, with the pH being adjusted from 4.0 to 7.4, the r2 value can be dramatically increased from 138.5 to 265.5 mM(-1) s(-1). The DOX-loaded hybrid nanogels also exhibit accelerated drug release in response to both pH reduction and temperature increase as a result of the substantial disruption of the interactions between drug molecules and copolymer components. With magnetic transport guidance toward the target and subsequent exposure to an alternating magnetic field, this DOX-loaded nanogel system possessing combined capabilities of hyperthermia and stimuli-triggered drug release showed superior in vitro cytotoxicity against HeLa cells as compared to the case with only free drug or hyperthermia alone. This work demonstrates that the hollow inorganic/organic hybrid nanogels hold great potential to serve as a multimodal theranostic vehicle functionalized with such desirable features as the guidable delivery of stimuli-mediated diagnostic imaging and hyperthermia/chemotherapies.

Thermo-responsive hydrogels for intravitreal injection and biomolecule release

NASA Astrophysics Data System (ADS)

Drapala, Pawel

In this dissertation, we develop an injectable polymer system to enable localized and prolonged release of therapeutic biomolecules for improved treatment of Age-Related Macular Degeneration (AMD). Thermo-responsive hydrogels derived from N-isopropylacrylamide (NIPAAm) and cross-linked with poly(ethylene glycol) (PEG) poly(L-Lactic acid) (PLLA) copolymer were synthesized via free-radical polymerization. These materials were investigated for (a) phase change behavior, (b) in-vitro degradation, (c) capacity for controlled drug delivery, and (d) biocompatibility. The volume-phase transition temperature (VPTT) of the PNIPAAm- co-PEG-b-PLLA hydrogels was adjusted using hydrophilic and hydrophobic moieties so that it is ca. 33°C. These hydrogels did not initially show evidence of degradation at 37°C due to physical cross-links of collapsed PNIPAAm. Only after addition of glutathione chain transfer agents (CTA)s to the precursor did the collapsed hydrogels become fully soluble at 37°C. CTAs significantly affected the release kinetics of biomolecules; addition of 1.0 mg/mL glutathione to 3 mM cross-linker accelerated hydrogel degradation, resulting in 100% release in less than 2 days. This work also explored the effect of PEGylation in order to tether biomolecules to the polymer matrix. It was demonstrated that non-site-specific PEGylation can postpone the burst release of solutes (up to 10 days in hydrogels with 0.5 mg/mL glutathione). Cell viability assays showed that at least two 20-minute buffer extraction steps were needed to remove cytotoxic elements from the hydrogels. Clinically-used therapeutic biomolecules LucentisRTM and AvastinRTM were demonstrated to be both stable and bioactive after release form PNIPAAm-co-PEG-b-PLLA hydrogels. The thermo-responsive hydrogels presented here offer a promising platform for the localized delivery of proteins such as recombinant antibodies.

Bifunctional polymer hydrogel layers as forward osmosis draw agents for continuous production of fresh water using solar energy.

PubMed

Razmjou, Amir; Liu, Qi; Simon, George P; Wang, Huanting

2013-11-19

The feasibility of bilayer polymer hydrogels as draw agent in forward osmosis process has been investigated. The dual-functionality hydrogels consist of a water-absorptive layer (particles of a copolymer of sodium acrylate and N-isopropylacrylamide) to provide osmotic pressure, and a dewatering layer (particles of N-isopropylacrylamide) to allow the ready release of the water absorbed during the FO drawing process at lower critical solution temperature (32 °C). The use of solar concentrated energy as the source of heat resulted in a significant increase in the dewatering rate as the temperature of dewatering layer increased to its LSCT more rapidly. Dewatering flux rose from 10 to 25 LMH when the solar concentrator increased the input energy from 0.5 to 2 kW/m(2). Thermodynamic analysis was also performed to find out the minimum energy requirement of such a bilayer hydrogel-driven FO process. This study represents a significant step forward toward the commercial implementation of hydrogel-driven FO system for continuous production of fresh water from saline water or wastewaters.

Material and fabrication strategies for artificial muscles (Conference Presentation)

NASA Astrophysics Data System (ADS)

Spinks, Geoffrey M.

2017-04-01

Soft robotic and wearable robotic devices seek to exploit polymer based artificial muscles and sensor materials to generate biomimetic movements and forces. A challenge is to integrate the active materials into a complex, three-dimensional device with integrated electronics, power supplies and support structures. Both 3D printing and textiles technologies offer attractive fabrication strategies, but require suitable functional materials. 3D printing of actuating hydrogels has been developed to produce simple devices, such as a prototype valve. Tough hydrogels based on interpenetrating networks of ionicially crosslinked alginate and covalently crosslinked polyacrylamide and poly(N-isopropylacrylamide) have been developed in a form suitable for extrusion printing with UV curing. Combined with UV-curable and extrudable rigid acrylated urethanes, the tough hydrogels can be 3D printed into composite materials or complex shapes with multiple different materials. An actuating valve was printed that operated thermally to open or close the flow path using 6 parallel hydrogel actuators. Textile processing methods such as knitting and weaving can be used to generate assemblies of actuating fibres. Low cost and high performance coiled fibres made from oriented polymers have been used for developing actuating textiles. Similarly, braiding methods have been developed to fabricate new forms of McKibben muscles that operate without any external apparatus, such as pumps, compressors or piping.

Smart responsive microcapsules capable of recognizing heavy metal ions.

PubMed

Pi, Shuo-Wei; Ju, Xiao-Jie; Wu, Han-Guang; Xie, Rui; Chu, Liang-Yin

2010-09-15

Smart responsive microcapsules capable of recognizing heavy metal ions are successfully prepared with oil-in-water-in-oil double emulsions as templates for polymerization in this study. The microcapsules are featured with thin poly(N-isopropylacrylamide-co-benzo-18-crown-6-acrylamide) (P(NIPAM-co-BCAm)) membranes, and they can selectively recognize special heavy metal ions such as barium(II) or lead(II) ions very well due to the "host-guest" complexation between the BCAm receptors and barium(II) or lead(II) ions. The stable BCAm/Ba(2+) or BCAm/Pb(2+) complexes in the P(NIPAM-co-BCAm) membrane cause a positive shift of the volume phase transition temperature of the crosslinked P(NIPAM-co-BCAm) hydrogel to a higher temperature, and the repulsion among the charged BCAm/Ba(2+) or BCAm/Pb(2+) complexes and the osmotic pressure within the P(NIPAM-co-BCAm) membranes result in the swelling of microcapsules. Induced by recognizing barium(II) or lead(II) ions, the prepared microcapsules with P(NIPAM-co-BCAm) membranes exhibit isothermal and significant swelling not only in outer and inner diameters but also in the membrane thickness. The proposed microcapsules in this study are highly attractive for developing smart sensors and/or carriers for detection and/or elimination of heavy metal ions. Copyright 2010 Elsevier Inc. All rights reserved.

Construction of optical glucose nanobiosensor with high sensitivity and selectivity at physiological pH on the basis of organic-inorganic hybrid microgels.

PubMed

Wu, Weitai; Zhou, Ting; Aiello, Michael; Zhou, Shuiqin

2010-08-15

A new class of optical glucose nanobiosensors with high sensitivity and selectivity at physiological pH is described. To construct these glucose nanobiosensors, the fluorescent CdS quantum dots (QDs), serving as the optical code, were incorporated into the glucose-sensitive poly(N-isopropylacrylamide-acrylamide-2-acrylamidomethyl-5-fluorophenylboronic acid) copolymer microgels, via both in situ growth method and "breathing in" method, respectively. The polymeric gel can adapt to surrounding glucose concentrations, and regulate the fluorescence of the embedded QDs, converting biochemical signals into optical signals. The gradual swelling of the gel would lead to the quenching of the fluorescence at the elevated glucose concentrations. The hybrid microgels displayed high selectivity to glucose over the potential primary interferents of lactate and human serum albumin in the physiologically important glucose concentration range. The stability, reversibility, and sensitivity of the organic-inorganic hybrid microgel-based biosensors were also systematically studied. These general properties of our nanobiosensors are well tunable under appropriate tailor on the hybrid microgels, in particular, simply through the change in the crosslinking degree of the microgels. The optical glucose nanobiosensors based on the organic-inorganic hybrid microgels have shown the potential for a third generation fluorescent biosensor. Copyright 2010 Elsevier B.V. All rights reserved.

Thermo-sensitive polymer nanospheres as a smart plugging agent for shale gas drilling operations.

PubMed

Wang, Wei-Ji; Qiu, Zheng-Song; Zhong, Han-Yi; Huang, Wei-An; Dai, Wen-Hao

2017-01-01

Emulsifier-free poly(methyl methacrylate-styrene) [P(MMA-St)] nanospheres with an average particle size of 100 nm were synthesized in an isopropyl alcohol-water medium by a solvothermal method. Then, through radical graft copolymerization of thermo-sensitive monomer N -isopropylacrylamide (NIPAm) and hydrophilic monomer acrylic acid (AA) onto the surface of P(MMA-St) nanospheres at 80 °C, a series of thermo-sensitive polymer nanospheres, named SD-SEAL with different lower critical solution temperatures (LCST), were prepared by adjusting the mole ratio of NIPAm to AA. The products were characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, thermogravimetric analysis, particle size distribution, and specific surface area analysis. The temperature-sensitive behavior was studied by light transmittance tests, while the sealing performance was investigated by pressure transmission tests with Lungmachi Formation shales. The experimental results showed that the synthesized nanoparticles are sensitive to temperature and had apparent LCST values which increased with an increase in hydrophilic monomer AA. When the temperature was higher than its LCST value, SD-SEAL played a dual role of physical plugging and chemical inhibition, slowed down pressure transmission, and reduced shale permeability remarkably. The plugged layer of shale was changed to being hydrophobic, which greatly improved the shale stability.

Development of Bench and Full-Scale Temperature and pH Responsive Functionalized PVDF Membranes with Tunable Properties

PubMed Central

Xiao, Li; Isner, Austin; Waldrop, Krysta; Saad, Anthony; Takigawa, Doreen; Bhattacharyya, Dibakar

2014-01-01

Temperature and pH responsive polymers (poly(N-isopropylacrylamide) (PNIPAAm), and polyacrylic acid, PAA) were synthesized in one common macrofiltration PVDF membrane platform by pore-filling method. The microstructure and morphology of the PNIPAAm-PVDF, and PNIPAAm-FPAA-PVDF membranes were studied by attenuated total reflectance Fourier transform infrared (ATR-FTIR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and atomic force microscopy (AFM). The membrane pore size was controlled by the swelling and shrinking of the PNIPAAm at the temperature around lower critical solution temperature (LCST). The composite membrane demonstrated a rapid and reversible swelling and deswelling change within a small temperature range. The controllable flux makes it possible to utilize this temperature responsive membrane as a valve to regulate filtration properties by temperature change. Dextran solution (Mw=2,000,000g/mol, 26 nm diameter) was used to evaluate the separation performance of the temperature responsive membranes. The ranges of dextran rejection are from 4% to 95% depending on the temperature, monomer amount and pressure. The full-scale membrane was also developed to confirm the feasibility of our bench-scale experimental results. The full-scale membrane also exhibited both temperature and pH responsivity. This system was also used for controlled nanoparticles synthesis and for dechlorination reaction. PMID:24944434

Infrared-spectroscopic single-shot laser mapping ellipsometry: Proof of concept for fast investigations of structured surfaces and interactions in organic thin films

NASA Astrophysics Data System (ADS)

Furchner, Andreas; Kratz, Christoph; Gkogkou, Dimitra; Ketelsen, Helge; Hinrichs, Karsten

2017-11-01

We present a novel infrared-spectroscopic laser mapping ellipsometer based on a single-shot measurement concept. The ellipsometric set-up employs multiple analyzers and detectors to simultaneously measure the sample's optical response under different analyzer azimuths. An essential component is a broadly tunable quantum cascade laser (QCL) covering the important marker region of 1800-1540 cm-1. The ellipsometer allows for fast single-wavelength as well as spectroscopic studies with thin-film sensitivity at temporal resolutions of 60 ms per wavelength. We applied the single-shot mapping ellipsometer for the characterization of metal-island enhancement surfaces as well as of molecular interactions in organic thin films. In less than 3 min, a linescan with 1600 steps revealed profile and infrared-enhancement properties of a gradient gold-island film for sensing applications. Spectroscopic measurements were performed to probe the amide I band of thin films of poly(N-isopropylacrylamide) [PNIPAAm], a stimuli-responsive polymer for bioapplications. The QCL spectra agree well with conventional FT-IR ellipsometric results, showing different band components associated with hydrogen-bond interactions between polymer and adsorbed water. Multi-wavelength ellipsometric maps were used to analyze homogeneity and surface contaminations of the polymer films.

Capture and release of cells using a temperature-responsive surface that immobilizes an antibody through DNA duplex formation.

PubMed

Kimura, Tsuyoshi; Nakamura, Naoko; Umeda, Kanji; Hashimoto, Yoshihide; Kishida, Akio

We synthesized a temperature-responsive surface that immobilized an antibody via DNA duplex formation for selective capture and release of target cells. Polyethylene films were modified by grafting poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPAAm-co-AAc)), which were prepared at various ratios of NIPAAm/AAc. The increased hydrophilicity of P(NIPAAm-co-PAA) film with decreased temperature was confirmed by water contact angle measurement. Single strand DNA (20mer) was chemically immobilized on the surface and then antibody (anti-mouse CD45, mCD45) modified with the complementary single strand DNA was immobilized on the surface through DNA duplex formation. The mCD45 antibody immobilization was confirmed by immunostaining. HeLa cells (mCD45 negative) and mouse bone marrow (BM) cells (mCD45 positive) were adhered on the surfaces at 37 °C. Although HeLa cells were detached by 4 °C incubation, BM cells were still adhered on the surface and then the adhered cells were released by DNase treatment. From these results, it was suggested that cells could be selectively captured and collected by using a film having surface that immobilizes an antibody via DNA duplex formation.

Effective interactions between soft-repulsive colloids: experiments, theory, and simulations.

PubMed

Mohanty, Priti S; Paloli, Divya; Crassous, Jérôme J; Zaccarelli, Emanuela; Schurtenberger, Peter

2014-03-07

We describe a combined experimental, theoretical, and simulation study of the structural correlations between cross-linked highly monodisperse and swollen Poly(N-isopropylacrylamide) microgel dispersions in the fluid phase in order to obtain the effective pair-interaction potential between the microgels. The density-dependent experimental pair distribution functions g(r)'s are deduced from real space studies using fluorescent confocal microscopy and compared with integral equation theory and molecular dynamics computer simulations. We use a model of Hertzian spheres that is capable to well reproduce the experimental pair distribution functions throughout the fluid phase, having fixed the particle size and the repulsive strength. Theoretically, a monodisperse system is considered whose properties are calculated within the Rogers-Young closure relation, while in the simulations the role of polydispersity is taken into account. We also discuss the various effects arising from the finite resolution of the microscope and from the noise coming from the fast Brownian motion of the particles at low densities, and compare the information content from data taken in 2D and 3D through a comparison with the corresponding simulations. Finally different potential shapes, recently adopted in studies of microgels, are also taken into account to assess which ones could also be used to describe the structure of the microgel fluid.

Magneto-thermally responsive hydrogels for bladder cancer treatment: Therapeutic efficacy and in vivo biodistribution.

PubMed

Jaiswal, Manish K; Pradhan, Lina; Vasavada, Shaleen; De, Mrinmoy; Sarma, H D; Prakash, Anand; Bahadur, D; Dravid, Vinayak P

2015-12-01

Bladder cancer is one of the deadliest forms of cancer in modern medicine which despite recent progress has remained incurable and challenging for researchers. There is unmet need to address this endemic as the number of patients are growing by about 10,000 every year world-wide. Here, we report a minimally invasive magnetic chemotherapy method to address this problem where polyethylene glycol (PEG) functionalized Fe3O4 magnetic nanostructures (MNS) are homogeneously embedded in thermally responsive poly(N-isopropylacrylamide, NIPAAm) hydrogels (HG). The system (HG-MNS) loaded with anti-cancer drug doxorubicin (DOX) incubated with cancer cell lines subjected to external radiofrequency (RF) field can remotely stimulate the release of drug smartly at the site. The in vitro efficacy investigated on bladder cancer (T-24) cell lines showed the potential of the system in dealing with the disease successfully. Further, the materials preferential accumulation via systemic delivery was studied using swiss mice model. Vital tissue organs like liver, lung and heart were analysed by magnetic resonance imaging (MRI). A detail accounts of the materials optimization, cytotoxicity and anti-proliferation activity tests with apoptosis analysis by flow cytometry after RF exposure (250 kHz) to the cells and in vivo biodistribution data are discussed in the paper. Copyright © 2015 Elsevier B.V. All rights reserved.

pH- and thermo-responsive microcontainers as potential drug delivery systems: Morphological characteristic, release and cytotoxicity studies.

PubMed

Efthimiadou, Eleni K; Tapeinos, Christos; Tziveleka, Leto-Aikaterini; Boukos, Nikos; Kordas, George

2014-04-01

Polymeric pH- and thermo-sensitive microcontainers (MCs) were developed as a potential drug delivery system for cancer therapy. It is well known that cancer cells exhibit notable characteristics such as acidic pH due to glycolytic cycle and higher temperature due to their higher proliferation rate. Based on these characteristics, we constructed a dual pH- and thermo-sensitive material for specific drug release on the pathological tissue. The MC's fabrication is based on a two-step procedure, in which, the first step involves the core synthesis and the second one is related to the shell formation. The core consists of poly(methyl methacrylate (PMMA), while the shell consists of PMMA, poly(isopropylacrylamide), poly(acrylic acid) and poly(divinylbenzene). Three different types of MCs were synthesized based on the seed polymerization method. The synthesized MCs were characterized structurally by Fourier transform infrared and morphologically by scanning electron microscopy. Dynamic light scattering was also used to study their behavior in aqueous solution under different pH and temperature conditions. For the loading and release study, the anthracycline drug daunorubicin (DNR) was used as a model drug, and its release properties were evaluated under different pH and thermo-conditions. Cytotoxicity studies were also carried out against MCF-7 breast cancer and 3T3 mouse embryonic fibroblast cells. According to our results, the synthesized microcontainers present desired pH and thermo behavior and can be applied in drug delivery systems. It is worth mentioning that the synthesized microcontainers which incorporated the drug DNR exhibit higher toxicity than the free drug. Copyright © 2014 Elsevier B.V. All rights reserved.

INFLUENCE OF LIPOPHILIC AND HYDROPHILIC CO-MONOMERS ON THE HYDRODYNAMIC DIAMETER OF THERMOSENSITIVE NIPA DERIVATIVES FOR THERMALLY CONTROLLED DRUG DELIVERY.

PubMed

Musial, Witold; Gasztych, Monika; Kokol, Vanja; Mucha, Igor; Makanis, Aleksandra; Kolodziejczyk, Woiciech; Gola, Agnieszka

2017-01-01

For modem drug delivery, new drug carriers sensitive to various factors and with size in the range of micro- and nanometers are required. The aim of this work was to evaluate the influence of hydrophilic and hydrophobic co-monomers on the hydrodynamic diameter of three co-polymers of N-isopropylacrylamide (NIPA) nanogels synthesized at 70*C in the presence of potassium persulfate (KPS) as the initiator and N.N'-methylene bis-acrylamide (MBA) as the cross-linker. The first batch of nanoparticles was synthesized without co-monomer, whereas poly(ethylene glycol) methyl ether acrylate (PEG-MEA), and N-teii-butylacrylamide (NTB), were implemented as co-monomers for the second and third batch. Hydrodynamic diameter of nanoparticles was in the range 550-800 rn. The compositions of the synthesized co-polymer nanoparticles were con- firmed via IR and NMR analyses. The SFPP conditions resulted in hydrodynamic diameters ranging from approximately 550 to 800 nm at temperatures lower than the volume phase transition temperature (VPTT) and diameters ranging from 250 to 600 nm at temperatures above the VPTT, where the VPTT was between 26 and 41'C. The polydispersity index (PDI) showed a maximum or a minimum value at the VPTT, which was an important indicator of the volume phase transition. According to the PDI observation during thermal cycling, the addition of NTB into the polymeric chain resulted in maximal values of the PDI at the VPIT, similar to the case of nanoparticles without any additional co-monomers. In contrast, in the case of PEG-MEA, the PDI presented a minimal value. Dynamic light scattering (DLS) volume measurements, performed simultaneously with spectral methods, may lead to a fast evaluation of nanoparticles prepared by SFPP.

A study on the reproducibility and spatial uniformity of N-isopropylacrylamide polymer gel dosimetry using a commercial 10X fast optical-computed tomography scanner

NASA Astrophysics Data System (ADS)

Chang, Y. J.; Lin, J. Q.; Hsieh, B. T.; Chen, C. H.

2013-06-01

This study investigated the reproducibility and spatial uniformity of N-isopropylacrylamide (NIPAM) polymer gel as well as the reproducibility of a NIPAM polymer gel dosimeter. A commercial 10X fast optical computed tomography scanner (OCTOPUS-10X, MGS Research, Inc., Madison, CT, USA) was used as the readout tool of the NIPAM polymer gel dosimeter. A cylindrical NIPAM gel phantom measuring 10 cm (diameter) by 10 cm (height) by 3 mm (thickness) was irradiated by the four-field box treatment with a field size of 3 cm × 3 cm. The dose profiles were found to be consistent at the depths of 2.0 cm to 5.0 cm for two independent gel phantom batches, and the average uncertainty was less than 2%. The gamma pass rates were calculated to be between 94% and 95% at depths of 40 mm for two independent gel phantom batches using 4% dose difference and 4 mm distance-to-agreement criterion. The NIPAM polymer gel dosimeter was highly reproducible and spatially uniform. The results highlighted the potential of the NIPAM polymer gel dosimeter in radiotherapy.

Effects of ions on the solubility transition and the phase-separation of N-isopropylacrylamide in water.

PubMed

Sasaki, Shigeo; Okabe, Satoshi

2011-11-10

The effects of NaCl, NaOH, and HCl on the solubility transition and the phase-separation of N-isopropylacrylamide (NIPA) were investigated for the purpose of clarifying the physicochemical mechanism of salting-out and salting-in phenomena. The discrete change in the solubility of NIPA in the salt-free water at the solubility transition (reported in J. Phys. Chem. B 2010, 114, 14995-15002) decreased with the addition of HCl and disappeared in the HCl solutions at concentrations higher than 2 M, while it increased with additions of NaOH and NaCl. A difference in NIPA concentration between the phase-separated solutions decreases with the addition of HCl and increases with additions of NaOH and NaCl. Partition coefficients of HCl in the phase-separated NIPA-rich solutions are higher than those in the NIPA poor solutions, while partition coefficients of NaCl and NaOH between the NIPA-rich and -poor solutions have trends opposite to those of HCl. The present results clearly indicate that the HCl favors the dehydrated NIPA and stabilizes the H(2)O-poor state of the NIPA molecule more than NaCl.

[Expression of acylamidase gene in Rhodococcus erythropolis strains].

PubMed

Lavrov, K V; Novikov, A D; Riabchenko, L E; Ianenko, A S

2014-09-01

The expression of a new acylamidase gene from R. erythropolis 37 was studied in Rhodococcus erythropolis strains. This acylamidase, as a result of its unique substrate specificity, can hydrolyse N-substituted amides (4'-nitroacetanilide, N-isopropylacrylamide, N'N-dimethylaminopropylacrylamide). A new expression system based on the use of the promoter region of nitrilhydratase genes from R. rhodochrous M8 was created to achieve constitutive synthesis of acylamidase in R. erythropolis cells. A fourfold improvement in the acylamidase activity of recombinant R. erythropolis cells as compared with the parent wild-type strain was obtained through the use of the new expression system.

Multi-input and -output logic circuits based on bioelectrocatalysis with horseradish peroxidase and glucose oxidase immobilized in multi-responsive copolymer films on electrodes.

PubMed

Yu, Xue; Lian, Wenjing; Zhang, Jiannan; Liu, Hongyun

2016-06-15

Herein, poly(N-isopropylacrylamide-co-N,N'-dimethylaminoethylmethacrylate) copolymer films were polymerized on electrode surface with a simple one-step method, and the enzyme horseradish peroxidase (HRP) was embedded in the films simultaneously, which were designated as P(NiPAAm-co-DMEM)-HRP. The films exhibited a reversible structure change with the external stimuli, such as pH, CO2, temperature and SO4(2-), causing the cyclic voltammetric (CV) response of electroactive K3Fe(CN)6 at the film electrodes to display the corresponding multi-stimuli sensitive ON-OFF behavior. Based on the switchable CV property of the system and the electrochemical reduction of H2O2 catalyzed by HRP in the films and mediated by Fe(CN)6(3-) in solution, a 5-input/3-output logic gate was established. To further increase the complexity of the logic system, another enzyme glucose oxidase (GOD) was added into the films, designated as P(NiPAAm-co-DMEM)-HRP-GOD. In the presence of oxygen, the oxidation of glucose in the solution was catalyzed by GOD in the films, and the produced H2O2 in situ was recognized and electrocatalytically reduced by HRP and mediated by Fe(CN)6(3-). Based on the bienzyme films, a cascaded or concatenated 4-input/3-output logic gate system was proposed. The present work combined the multi-responsive interface with bioelectrocatalysis to construct cascaded logic circuits, which might open a new avenue to develop biocomputing elements with more sophisticated functions and design novel glucose biosensors. Copyright © 2016 Elsevier B.V. All rights reserved.

Temperature-responsive chromatography for the separation of biomolecules.

PubMed

Kanazawa, Hideko; Okano, Teruo

2011-12-09

Temperature-responsive chromatography for the separation of biomolecules utilizing poly(N-isopropylacrylamide) (PNIPAAm) and its copolymer-modified stationary phase is performed with an aqueous mobile phase without using organic solvent. The surface properties and function of the stationary phase are controlled by external temperature changes without changing the mobile-phase composition. This analytical system is based on nonspecific adsorption by the reversible transition of a hydrophilic-hydrophobic PNIPAAm-grafted surface. The driving force for retention is hydrophobic interaction between the solute molecules and the hydrophobized polymer chains on the stationary phase surface. The separation of the biomolecules, such as nucleotides and proteins was achieved by a dual temperature- and pH-responsive chromatography system. The electrostatic and hydrophobic interactions could be modulated simultaneously with the temperature in an aqueous mobile phase, thus the separation system would have potential applications in the separation of biomolecules. Additionally, chromatographic matrices prepared by a surface-initiated atom transfer radical polymerization (ATRP) exhibit a strong interaction with analytes, because the polymerization procedure forms a densely packed polymer, called a polymer brush, on the surfaces. The copolymer brush grafted surfaces prepared by ATRP was an effective tool for separating basic biomolecules by modulating the electrostatic and hydrophobic interactions. Applications of thermally responsive columns for the separations of biomolecules are reviewed here. Copyright © 2011 Elsevier B.V. All rights reserved.

PNIPAAm-MAA nanoparticles as delivery vehicles for curcumin against MCF-7 breast cancer cells.

PubMed

Zeighamian, Vahideh; Darabi, Masoud; Akbarzadeh, Abolfazl; Rahmati-Yamchi, Mohammad; Zarghami, Nosratollah; Badrzadeh, Fariba; Salehi, Roya; Mirakabad, Fatemeh Sadat Tabatabaei; Taheri-Anganeh, Mortaza

2016-01-01

Breast cancer is the most frequently occurring cancer among women throughout the world. Natural compounds such as curcumin hold promise to treat a variety of cancers including breast cancer. However, curcumin's therapeutic application is limited, due to its rapid degradation and poor aqueous solubility. On the other hand, previous studies have stated that drug delivery using nanoparticles might improve the therapeutic response to anticancer drugs. Poly(N-isopropylacrylamide-co-methacrylic acid) (PNIPAAm-MAA) is one of the hydrogel copolymers utilized in the drug delivery system for cancer therapy. The aim of this study was to examine the cytotoxic potential of curcumin encapsulated within the NIPAAm-MAA nanoparticle, on the MCF-7 breast cancer cell line. In this work, polymeric nanoparticles were synthesized through the free radical mechanism, and curcumin was encapsulated into NIPAAm-MAA nanoparticles. Then, the cytotoxic effect of curcumin-loaded NIPAAm-MAA on the MCF-7 breast cancer cell line was measured by MTT assays. The evaluation of the results showed that curcumin-loaded NIPAAm-MAA has more cytotoxic effect on the MCF-7 cell line and efficiently inhibited the growth of the breast cancer cell population, compared with free curcumin. In conclusion, this study indicates that curcumin-loaded NIPAAm-MAA suppresses the growth of the MCF-7 cell line. Overall, it is concluded that encapsulating curcumin into the NIPAAm-MAA copolymer could open up new avenues for breast cancer treatment.

The effect of glutathione as chain transfer agent in PNIPAAm-based thermo-responsive hydrogels for controlled release of proteins.

PubMed

Drapala, Pawel W; Jiang, Bin; Chiu, Yu-Chieh; Mieler, William F; Brey, Eric M; Kang-Mieler, Jennifer J; Pérez-Luna, Victor H

2014-03-01

To control degradation and protein release using thermo-responsive hydrogels for localized delivery of anti-angiogenic proteins. Thermo-responsive hydrogels derived from N-isopropylacrylamide (NIPAAm) and crosslinked with poly(ethylene glycol)-co-(L-lactic acid) diacrylate (Acry-PLLA-b-PEG-b-PLLA-Acry) were synthesized via free radical polymerization in the presence of glutathione, a chain transfer agent (CTA) added to modulate their degradation and release properties. Immunoglobulin G (IgG) and the recombinant proteins Avastin® and Lucentis® were encapsulated in these hydrogels and their release was studied. The encapsulation efficiency of IgG was high (75-87%) and decreased with CTA concentration. The transition temperature of these hydrogels was below physiological temperature, which is important for minimally invasive therapies involving these materials. The toxicity from unreacted monomers and free radical initiators was eliminated with a minimum of three buffer extractions. Addition of CTA accelerated degradation and resulted in complete protein release. Glutathione caused the degradation products to become solubilized even at 37°C. Hydrogels prepared without glutathione did not disintegrate nor released protein completely after 3 weeks at 37°C. PEGylation of IgG postponed the burst release effect. Avastin® and Lucentis® released from degraded hydrogels retained their biological activity. These systems offer a promising platform for the localized delivery of proteins.

Preparation and Characterization of Thermoresponsive Poly(N-isopropylacrylamide-co-acrylic acid)-Grafted Hollow Fe3O4/SiO2 Microspheres with Surface Holes for BSA Release

PubMed Central

Zhao, Jing; Zeng, Ming; Zheng, Kaiqiang; He, Xinhua; Xie, Minqiang; Fu, Xiaoyi

2017-01-01

Thermoresponsive P(NIPAM-AA)/Fe3O4/SiO2 microspheres with surface holes serving as carriers were prepared using p-Fe3O4/SiO2 microspheres with a thermoresponsive copolymer. The p-Fe3O4/SiO2 microspheres was obtained using a modified Pickering method and chemical etching. The surface pore size of p-Fe3O4/SiO2 microspheres was in the range of 18.3 nm~37.2 nm and the cavity size was approximately 60 nm, which are suitable for loading and transporting biological macromolecules. P(NIPAM-AA) was synthesized inside and outside of the p-Fe3O4/SiO2 microspheres via atom transfer radical polymerization of NIPAM, MBA and AA. The volume phase transition temperature (VPTT) of the specifically designed P(NIPAM-AA)/Fe3O4/SiO2 microspheres was 42.5 °C. The saturation magnetization of P(NIPAM-AA)/Fe3O4/SiO2 microspheres was 72.7 emu/g. The P(NIPAM-AA)/Fe3O4/SiO2 microspheres were used as carriers to study the loading and release behavior of BSA. This microsphere system shows potential for the loading of proteins as a drug delivery platform. PMID:28772770

A Robust Method to Generate Mechanically Anisotropic Vascular Smooth Muscle Cell Sheets for Vascular Tissue Engineering.

PubMed

Backman, Daniel E; LeSavage, Bauer L; Shah, Shivem B; Wong, Joyce Y

2017-06-01

In arterial tissue engineering, mimicking native structure and mechanical properties is essential because compliance mismatch can lead to graft failure and further disease. With bottom-up tissue engineering approaches, designing tissue components with proper microscale mechanical properties is crucial to achieve the necessary macroscale properties in the final implant. This study develops a thermoresponsive cell culture platform for growing aligned vascular smooth muscle cell (VSMC) sheets by photografting N-isopropylacrylamide (NIPAAm) onto micropatterned poly(dimethysiloxane) (PDMS). The grafting process is experimentally and computationally optimized to produce PNIPAAm-PDMS substrates optimal for VSMC attachment. To allow long-term VSMC sheet culture and increase the rate of VSMC sheet formation, PNIPAAm-PDMS surfaces were further modified with 3-aminopropyltriethoxysilane yielding a robust, thermoresponsive cell culture platform for culturing VSMC sheets. VSMC cell sheets cultured on patterned thermoresponsive substrates exhibit cellular and collagen alignment in the direction of the micropattern. Mechanical characterization of patterned, single-layer VSMC sheets reveals increased stiffness in the aligned direction compared to the perpendicular direction whereas nonpatterned cell sheets exhibit no directional dependence. Structural and mechanical anisotropy of aligned, single-layer VSMC sheets makes this platform an attractive microstructural building block for engineering a vascular graft to match the in vivo mechanical properties of native arterial tissue. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In vivo Pharmacological Evaluations of Pilocarpine-Loaded Antioxidant-Functionalized Biodegradable Thermogels in Glaucomatous Rabbits

NASA Astrophysics Data System (ADS)

Chou, Shih-Feng; Luo, Li-Jyuan; Lai, Jui-Yang

2017-02-01

To alleviate oxidative stress-induced ocular hypertension, grafting of antioxidant molecules to drug carriers enables a dual-function mechanism to effectively treat glaucomatous intraocular pressure (IOP) dysregulation. Providing potential application for intracameral administration of antiglaucoma medications, this study, for the first time, aims to examine in vivo pharmacological efficacy of pilocarpine-loaded antioxidant-functionalized biodegradable thermogels in glaucomatous rabbits. A series of gallic acid (GA)-grafted gelatin-g-poly(N-isopropylacrylamide) (GN) polymers were synthesized via redox reactions at 20-50 °C. Our results showed that raising redox radical initiation reaction temperature maximizes GA grafting level, antioxidant activity, and water content at 40 °C. Meanwhile, increase in overall hydrophilicity of GNGA carriers leads to fast polymer degradation and early pilocarpine depletion in vivo, which is disadvantageous to offer necessary pharmacological performance at prolonged time. By contrast, sustained therapeutic drug concentrations in aqueous humor can be achieved for long-term (i.e., 28 days) protection against corneal aberration and retinal injury after pilocarpine delivery using dual-function optimized carriers synthesized at 30 °C. The GA-functionalized injectable hydrogels are also found to contribute significantly to enhancement of retinal antioxidant defense system and preservation of histological structure and electrophysiological function, thereby supporting the benefits of drug-containing antioxidant biodegradable thermogels to prevent glaucoma development.

Plasmonic Library Based on Substrate-Supported Gradiential Plasmonic Arrays

PubMed Central

2014-01-01

We present a versatile approach to produce macroscopic, substrate-supported arrays of plasmonic nanoparticles with well-defined interparticle spacing and a continuous particle size gradient. The arrays thus present a “plasmonic library” of locally noncoupling plasmonic particles of different sizes, which can serve as a platform for future combinatorial screening of size effects. The structures were prepared by substrate assembly of gold-core/poly(N-isopropylacrylamide)-shell particles and subsequent post-modification. Coupling of the localized surface plasmon resonance (LSPR) could be avoided since the polymer shell separates the encapsulated gold cores. To produce a particle array with a broad range of well-defined but laterally distinguishable particle sizes, the substrate was dip-coated in a growth solution, which resulted in an overgrowth of the gold cores controlled by the local exposure time. The kinetics was quantitatively analyzed and found to be diffusion rate controlled, allowing for precise tuning of particle size by adjusting the withdrawal speed. We determined the kinetics of the overgrowth process, investigated the LSPRs along the gradient by UV–vis extinction spectroscopy, and compared the spectroscopic results to the predictions from Mie theory, indicating the absence of local interparticle coupling. We finally discuss potential applications of these substrate-supported plasmonic particle libraries and perspectives toward extending the concept from size to composition variation and screening of plasmonic coupling effects. PMID:25137554

Temperature-dependent optical properties of gold nanoparticles coated with a charged diblock copolymer and an uncharged triblock copolymer.

PubMed

Volden, Sondre; Kjøniksen, Anna-Lena; Zhu, Kaizheng; Genzer, Jan; Nyström, Bo; Glomm, Wilhelm R

2010-02-23

We demonstrate that the optical properties of gold nanoparticles can be used to detect and follow stimuli-induced changes in adsorbed macromolecules. Specifically, we investigate thermal response of anionic diblock and uncharged triblock copolymers based on poly(N-isopropylacrylamide) (PNIPAAM) blocks adsorbed onto gold nanoparticles and planar gold surfaces in a temperature range between 25 and 60 degrees C. By employing a palette of analytical probes, including UV-visible spectroscopy, dynamic light scattering, fluorescence, and quartz crystal microbalance with dissipation monitoring, we establish that while the anionic copolymer forms monolayers at both low and high temperature, the neutral copolymer adsorbs as a monolayer at low temperatures and forms multilayers above the cloud point (T(C)). Raising the temperature above T(C) severely affects the optical properties of the gold particle/polymer composites, expelling associated water and altering the immediate surroundings of the gold nanoparticles. This effect, stronger for the uncharged polymer, is related to the amount of polymer adsorbed on the surface, where a denser shell influences the surface plasmon band to a greater degree. This is corroborated with light scattering experiments, which reveal that flocculation of the neutral polymer-coated particles occurs at high temperatures. The flocculation behavior of the neutral copolymer on planar gold surfaces results in multilayer formation. The observed effects are discussed within the framework of the Mie-Drude theory.

Self-rolling up micro 3D structures using temperature-responsive hydrogel sheet

NASA Astrophysics Data System (ADS)

Iwata, Y.; Miyashita, S.; Iwase, E.

2017-12-01

This paper proposes a micro self-folding using a self-rolling up deformation. In the fabrication method at micro scale, self-folding is an especially useful method of easily fabricating complex three-dimensional (3D) structures from engineered two-dimensional (2D) sheets. However, most self-folded structures are limited to 3D structures with a hollow region. Therefore, we made 3D structures with a small hollow region by self-rolling up a 2D sheet consisting of SU-8 and a temperature-responsive hybrid hydrogel of poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAM-AAc). The temperature-responsive hydrogel can provide repetitive deformation, which is a good feature for micro soft robots or actuators, using hydrogel shrinking and swelling. Our micro self-rolling up method is a self-folding method for a 3D structure performed by rolling up a 2D flat sheet, like making a croissant, through continuous self-folding. We used our method to fabricate 3D structures with a small hollow region, such as cylindrical, conical, and croissant-like ellipsoidal structures, and 3D structures with a hollow region, such as spiral shapes. All the structures showed repetitive deformation, forward rolling up in 20 °C cold water and backward rolling up in 40 °C hot water. The results demonstrate that self-rolling up deformation can be useful in the field of micro soft devices.

Temperature-Switchable Agglomeration of Magnetic Particles Designed for Continuous Separation Processes in Biotechnology.

PubMed

Paulus, Anja S; Heinzler, Raphael; Ooi, Huey Wen; Franzreb, Matthias

2015-07-08

The purpose of this work was the synthesis and characterization of thermally switchable magnetic particles for use in biotechnological applications such as protein purification and enzymatic conversions. Reversible addition-fragmentation chain-transfer polymerization was employed to synthesize poly(N-isopropylacrylamide) brushes via a "graft-from" approach on the surface of magnetic microparticles. The resulting particles were characterized by infrared spectroscopy and thermogravimetric analysis and their temperature-dependent agglomeration behavior was assessed. The influence of several factors on particle agglomeration (pH, temperature, salt type, and particle concentration) was evaluated. The results showed that a low pH value (pH 3-4), a kosmotropic salt (ammonium sulfate), and a high particle concentration (4 g/L) resulted in improved agglomeration at elevated temperature (40 °C). Recycling of particles and reversibility of the temperature-switchable agglomeration were successfully demonstrated for ten heating-cooling cycles. Additionally, enhanced magnetic separation was observed for the modified particles. Ionic monomers were integrated into the polymer chain to create end-group functionalized particles as well as two- and three-block copolymer particles for protein binding. The adsorption of lactoferrin, bovine serum albumin, and lysozyme to these ion exchange particles was evaluated and showed a binding capacity of up to 135 mg/g. The dual-responsive particles combined magnetic and thermoresponsive properties for switchable agglomeration, easy separability, and efficient protein adsorption.

Synthesis of Thermally Switchable Chromatographic Materials with Immobilized Ti4+ for Enrichment of Phosphopeptides by Reversible Addition Fragmentation Chain Transfer Polymerization

NASA Astrophysics Data System (ADS)

Wang, Di; Cao, Zhihan; Pang, Xinzhu; Deng, Yulin; Li, Bo; Dai, Rongji

2018-01-01

Reversible phosphorylation of proteins is one of the most crucial types of post-translational modifications (PTMs). And it shows significant work in diversified biological processes. However, the separation technology of phosphorylated peptides is still an analytical challenge in phosphoproteomics, because phosphopeptides are alway in low stoichiometry. Thus, enrichment of phosphopeptides before detection is indispensable. In this study, a novel temperature regulated separation protocol was developed. Silica@p (NIPAAm-co-IPPA)-Ti4+, a new Ti(IV)-IMAC (Immobilized Metal Affinity chromatography) materials was synthesized by reversible addition fragmentation chain transfer polymerization (RAFT). By the unique thermally responsive properties of poly(N-isopropylacrylamide) (PNIPAAm), the captured phosphorylated peptides could be released by changing temperature only without applying any other eluant which could damage the phosphopeptides. We employed isopropanol phosphonic acid (IPPA) as an IMAC ligand for the immobilization of Ti(IV) which could increase the specific adsorption of phosphopeptides. The enrichment and release properties were examined by treatment with pyridoxal 5’-phosphate (PLP) and casein phosphopeptides (CPP). Two phosphorylated compounds above have temperature-stimulated binding to Ti4+. Finally, silica@p (NIPAAm-co-IPPA)-Ti4+ was successfully employed in pretreatment of phosphopeptides in a tryptic digest of a-casein and human serum albumin (HSA). The results indicated a great potential of this new temperature-responsive material in phosphoproteomics study.

[Stimuli sensitive changes in electrical surface properties of soft membranes: from a synthesized polymer to a biological system].

PubMed

Makino, K

1997-01-01

The electrical surface properties of biological cells have been studied, which provided us with the fundamental knowledge about the cell surface. The change in shape or biological functions of cells may affect the surface properties and can be detected by electrokinetic measurements. Biological cell surfaces are covered with polysaccharide chains, some are charged and some are not. Some polysaccharides produce a hydrogel matrixes under a proper condition. We thus consider it reasonable that cell surface is approximated by a hydrogel surface. Electrophoretic mobility measurements are useful for studying the surface properties of biological cells suspended as colloidal particles in an electrolyte solution. The electro-osmotic velocity measurements on the other hand are advantageous to the study of the surface properties of slab-shaped biological systems such as membranes. This work was started with a hydrogel, as a model material. As a hydrogel, poly(N-isopropylacrylamide) poly(NIPAAm), abbreviated as hereafter, was chosen, because this hydrogel changes its volume depending on temperature. The dependence of the electrophoretic mobility of latex particles covered with poly(NIPAAm) hydrogel layer or of the electro-osmotic mobility on poly(NIPAAm) plate upon temperature and ionic strength of the dispersing medium was well explained with an electrophoretic mobility formula for "soft particles" developed by Ohshima. The electrokinetic measurements and the explanation of data with an electrophoretic mobility formula for "soft particles" give us information about the surface charge density and the "softness" of soft surfaces. On the basis of the findings with hydrogels, we have discussed the relationship between the changes in shape or function of the biological cells and the change in physicochemical surface properties using these measurements. To study the change in physicochemical properties of the cell surface caused by apoptosis, we have measured the electrophoretic mobilities of intact and apoptotic human promyelocytic leukemia cell lines, HL-60RG cells. We have also studied the differences observed in surface properties of malignant lymphosarcoma cell line, RAW117-P, and its variant, RAW117-H10, with a high metastatic property to the liver. In both cases, the cell surfaces became softer by the changes of biological functions. We have applied electrophoresis and electro-osmosis measurements to the study of the electrokinetic surface properties of rat basophilic leukemia cells, RBL cells. It was also found that the surface of Human umbilical vein endothelial cells, HUVEC, is considerably soft as compared with those of other biological cells we have studied before.

Thermal and pH responsive polymer-tethered multifunctional magnetic nanoparticles for targeted delivery of anticancer drug.

PubMed

Sahoo, Banalata; Devi, K Sanjana P; Banerjee, Rakesh; Maiti, Tapas K; Pramanik, Panchanan; Dhara, Dibakar

2013-05-01

Targeted and efficient delivery of therapeutics to tumor cells is one of the key issues in cancer therapy. In the present work, we report a temperature and pH dual responsive core-shell nanoparticles comprising smart polymer shell coated on magnetic nanoparticles as an anticancer drug carrier and cancer cell-specific targeting agent. Magnetite nanoparticles (MNPs), prepared by a simple coprecipitation method, was surface modified by introducing amine groups using 3-aminopropyltriethoxysilane. Dual-responsive poly(N-isopropylacrylamide)-block-poly(acrylic acid) copolymer, synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization, was then attached to the amine-functionalized MNPs via EDC/NHS method. Further, to accomplish cancer-specific targeting properties, folic acid was tethered to the surface of the nanoparticles. Thereafter, rhodamine B isothiocyanate was conjugated to endow fluorescent property to the MNPs required for cellular imaging applications. The nanoparticles were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), selected area electron diffraction (SAED), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA), zeta potential, vibrating sample magnetometer (VSM), X-ray photoelectron spectroscopy (XPS) measurements, and FTIR, UV-vis spectral analysis. Doxorubicin (DOX), an anticancer drug used for the present study, was loaded into the nanoparticles and its release behavior was subsequently studied. Result showed a sustained release of DOX preferentially at the desired lysosomal pH and temperature condition. The biological activity of the DOX-loaded MNPs was studied by MTT assay, fluorescence microscopy, and apoptosis. Intracellular-uptake studies revealed preferential uptake of these nanoparticles into cancer cells (HeLa cells) compared to normal fibroblast cells (L929 cells). The in vitro apoptosis study revealed that the DOX-loaded nanoparticles caused significant death to the HeLa cells. These nanoparticles were capable of target specific release of the loaded drug in response to pH and temperature and hence may serve as a potential drug carrier for in vivo applications.

Antibody loaded collapsible hyaluronic acid hydrogels for intraocular delivery.

PubMed

Egbu, Raphael; Brocchini, Steve; Khaw, Peng T; Awwad, Sahar

2018-03-01

Injectable gels have the potential to encapsulate drugs for sustained release of protein therapeutics for use in the eye. Hyaluronic acid (HA) is a biodegradable clinically used material and poly N-isopropylacrylamide (pNIPAAM) is a stimuli responsive polymer that can display a lower critical solution temperature (LCST) at physiological conditions. Two gel systems incorporating HA were prepared in the presence of the antibody infliximab (INF): i) 1% and 5% tyramine-substituted HA (HA-Tyr) was enzymatically crosslinked in the presence of INF to form HA-Tyr-INF and ii) NIPAAM was chemically crosslinked in the presence of HA and INF with 1 and 3% poly(ethylene glycol) diacrylate (PEGDA) to form PEGDA-pNIPAAM-HA-INF. The PEGDA-pNIPAAM-HA-INF hydrogels displayed LCSTs at temperatures ranging from 31.4 ± 0.2 to 35.7 ± 0.3 °C. Although all the gels prepared were injectable, INF-loaded gels with lower crosslinking density (1% PEGDA-pNIPAAM-HA and 1% HA-Tyr) showed lower elastic (G') and viscous (G″) moduli compared to higher crosslinked gels (3% PEGDA-pNIPAAM-HA-INF and 5% HA-Tyr-INF) resulting in differences in swelling ratio (SR). Moduli may be correlated with overall stiffness of the gel. All hydrogels demonstrated sustained release of INF in a two-compartment in vitro outflow model of the human eye called the PK-Eye. The 1% PEGDA-pNIPAAM-HA-INF hydrogel displayed the slowest release (24.9 ± 0.4% INF release by day 9) in phosphate buffered saline (PBS, pH 7.4), which is a better release profile than the free drug alone (tested under the same conditions). These results suggest that PEGDA-pNIPAAM-HA has potential for the continued development of formulations to prolong the intraocular release of proteins. Copyright © 2017 Elsevier B.V. All rights reserved.

A dual pH and temperature responsive polymeric fluorescent sensor and its imaging application in living cells.

PubMed

Yin, Liyan; He, Chunsheng; Huang, Chusen; Zhu, Weiping; Wang, Xin; Xu, Yufang; Qian, Xuhong

2012-05-11

A polymeric fluorescent sensor PNME, consisting of A4 and N-isopropylacrylamide (NIPAM) units, was synthesized. PNME exhibited dual responses to pH and temperature, and could be used as an intracellular pH sensor for lysosomes imaging. Moreover, it also could sense different temperature change in living cells at 25 and 37 °C, respectively. This journal is © The Royal Society of Chemistry 2012

Photopolymerization Synthesis of Magnetic Nanoparticle Embedded Nanogels for Targeted Biotherapeutic Delivery

NASA Astrophysics Data System (ADS)

Denmark, Daniel J.

Conventional therapeutic techniques treat the patient by delivering a biotherapeutic to the entire body rather than the target tissue. In the case of chemotherapy, the biotherapeutic is a drug that kills healthy and diseased cells indiscriminately which can lead to undesirable side effects. With targeted delivery, biotherapeutics can be delivered directly to the diseased tissue significantly reducing exposure to otherwise healthy tissue. Typical composite delivery devices are minimally composed of a stimuli responsive polymer, such as poly(N-isopropylacrylamide), allowing for triggered release when heated beyond approximately 32 °C, and magnetic nanoparticles which enable targeting as well as provide a mechanism for stimulus upon alternating magnetic field heating. Although more traditional methods, such as emulsion polymerization, have been used to realize these composite devices, the synthesis is problematic. Poisonous surfactants that are necessary to prevent agglomeration must be removed from the finished polymer, increasing the time and cost of the process. This study seeks to further explore non-toxic, biocompatible, non-residual, photochemical methods of creating stimuli responsive nanogels to advance the targeted biotherapeutic delivery field. Ultraviolet photopolymerization promises to be more efficient, while ensuring safety by using only biocompatible substances. The reactants selected for nanogel fabrication were N -isopropylacrylamide as monomer, methylene bisacrylamide as cross-linker, and Irgacure 2959 as ultraviolet photo-initiator. The superparamagnetic nanoparticles for encapsulation were approximately 10 nm in diameter and composed of magnetite to enable remote delivery and enhanced triggered release properties. Early investigations into the interactions of the polymer and nanoparticles employ a pioneering experimental setup, which allows for coincident turbidimetry and alternating magnetic field heating of an aqueous solution containing both materials. Herein, a low-cost, scalable, and rapid, custom ultraviolet photo-reactor with in-situ, spectroscopic monitoring system is used to observe the synthesis as the sample undergoes photopolymerization. This method also allows in-situ encapsulation of the magnetic nanoparticles simplifying the process. Size characterization of the resulting nanogels was performed by Transmission Electron Microscopy revealing size-tunable nanogel spheres between 50 and 800 nm by varying the ratio and concentration of the reactants. Nano-Tracking Analysis indicates that the nanogels exhibit minimal agglomeration as well as provides a temperature-dependent particle size distribution. Optical characterization utilized Fourier Transform Infrared and Ultraviolet Spectroscopy to confirm successful polymerization. When samples of the nanogels encapsulating magnetic nanoparticles were subjected to an alternating magnetic field a temperature increase was observed indicating that triggered release is possible. Furthermore, a model, based on linear response theory that innovatively utilizes size distribution data, is presented to explain alternating magnetic field heating results. The results presented here will advance targeted biotherapeutic delivery and have a wide range of applications in medical sciences like oncology, gene delivery, cardiology and endocrinology.

Recyclable Thermoresponsive Polymer-Cellulase Bioconjugates for Biomass Depolymerization

PubMed Central

Mackenzie, Katherine J.; Francis, Matthew B.

2013-01-01

Here we report the construction and characterization of a recoverable, thermoresponsive polymer-endoglucanase bioconjugate that matches the activity of unmodified enzymes on insoluble cellulose substrates. Two copolymers exhibiting a thermoresponsive lower critical solution temperature (LCST) were created through the copolymerization of an aminooxy-bearing methacrylamide with N-isopropylacrylamide (NIPAm) or N-isopropylmethacrylamide (NIPMa). The aminooxy group provided a handle through which the LCST was adjusted through small-molecule quenching. This allowed materials with LCSTs ranging from 20.9 °C to 60.5 °C to be readily obtained after polymerization. The thermostable endoglucanase EGPh from the hypothermophilic Pyrococcus horikoshii was transaminated with pyridoxal-5’-phosphate to produce a ketone-bearing protein, which was then site-selectively modified through oxime linkage with benzylalkoxyamine or 5 kDa-poly(ethylene glycol)-alkoxyamine. These modified proteins showed activity comparable to the controls when assayed on an insoluble cellulosic substrate. Two polymer bioconjugates were then constructed using transaminated EGPh and the aminooxy-bearing copolymers. After twelve hours, both bioconjugates produced an equivalent amount of free reducing sugars as the unmodified control using insoluble cellulose as a substrate. The recycling ability of the NIPAm copolymer-EGPh conjugate was determined through three rounds of activity, maintaining over 60% activity after two cycles of reuse and affording significantly more soluble carbohydrates than unmodified enzyme alone. When assayed on acid-pretreated Miscanthus, this bioconjugate increased the amount of reducing sugars by 2.8-fold over three rounds of activity. The synthetic strategy of this bioconjugate allows the LCST of the material to be changed readily from a common stock of copolymer and the method of attachment is applicable to a variety of proteins, enabling the same approach to be amenable to thermophile-derived cellulases or to the separation of multiple species using polymers with different recovery temperatures. PMID:23270527

Edge-Hydroxylated Boron Nitride Nanosheets as an Effective Additive to Improve the Thermal Response of Hydrogels.

PubMed

Xiao, Feng; Naficy, Sina; Casillas, Gilberto; Khan, Majharul H; Katkus, Tomas; Jiang, Lei; Liu, Huakun; Li, Huijun; Huang, Zhenguo

2015-11-25

Upon flowing hot steam over hexagonal boron nitride (h-BN) bulk powder, efficient exfoliation and hydroxylation of BN occur simultaneously. Through effective hydrogen bonding with water and N-isopropylacrylamide, edge-hydroxylated BN nanosheets dramatically improve the dimensional change and dye release of this temperature-sensitive hydrogel and thereby enhance its efficacy in bionic, soft robotic, and drug-delivery applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Thermoresponsive, in situ crosslinkable hydrogels based on N-isopropylacrylamide: Fabrication, characterization and mesenchymal stem cell encapsulation

PubMed Central

Klouda, Leda; Perkins, Kevin R.; Watson, Brendan M.; Hacker, Michael C.; Bryant, Stephanie J.; Raphael, Robert M.; Kasper, F. Kurtis; Mikos, Antonios G.

2011-01-01

Hydrogels that solidify in response to a dual, physical and chemical, mechanism upon temperature increase were fabricated and characterized. The hydrogels were based on N-isopropylacrylamide, which renders them thermoresponsive, and contained covalently crosslinkable moieties in the macromers. The effects of the macromer end group, namely acrylate or methacrylate, and the fabrication conditions were investigated on the degradative and swelling properties of the hydrogels. The hydrogels exhibited higher swelling below their lower critical solution temperature (LCST). When immersed in cell culture media at physiological temperature, which was above their LCST, hydrogels showed constant swelling and no degradation over eight weeks, with methacrylated hydrogels having higher swelling than their acrylated analogs. In addition, hydrogels immersed in cell culture media under the same conditions showed lower swelling as compared to phosphate buffered saline. The interplay between chemical crosslinking and thermally induced phase separation affected the swelling characteristics of hydrogels in different media. Mesenchymal stem cells encapsulated in the hydrogels in vitro were viable over three weeks and markers of osteogenic differentiation were detected when the cells were cultured with osteogenic supplements. Hydrogel mineralization in the absence of cells was observed in cell culture medium with the addition of fetal bovine serum and β-glycerol phosphate. The results suggest that these hydrogels may be suitable as carriers for cell delivery in tissue engineering. PMID:21187170

Laser heating tunability by off-resonant irradiation of gold nanoparticles.

PubMed

Hormeño, Silvia; Gregorio-Godoy, Paula; Pérez-Juste, Jorge; Liz-Marzán, Luis M; Juárez, Beatriz H; Arias-Gonzalez, J Ricardo

2014-01-29

Temperature changes in the vicinity of a single absorptive nanostructure caused by local heating have strong implications in technologies such as integrated electronics or biomedicine. Herein, the temperature changes in the vicinity of a single optically trapped spherical Au nanoparticle encapsulated in a thermo-responsive poly(N-isopropylacrylamide) shell (Au@pNIPAM) are studied in detail. Individual beads are trapped in a counter-propagating optical tweezers setup at various laser powers, which allows the overall particle size to be tuned through the phase transition of the thermo-responsive shell. The experimentally obtained sizes measured at different irradiation powers are compared with average size values obtained by dynamic light scattering (DLS) from an ensemble of beads at different temperatures. The size range and the tendency to shrink upon increasing the laser power in the optical trap or by increasing the temperature for DLS agree with reasonable accuracy for both approaches. Discrepancies are evaluated by means of simple models accounting for variations in the thermal conductivity of the polymer, the viscosity of the aqueous solution and the absorption cross section of the coated Au nanoparticle. These results show that these parameters must be taken into account when considering local laser heating experiments in aqueous solution at the nanoscale. Analysis of the stability of the Au@pNIPAM particles in the trap is also theoretically carried out for different particle sizes. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Light-induced spatial control of pH-jump reaction at smart gel interface.

PubMed

Techawanitchai, Prapatsorn; Ebara, Mitsuhiro; Idota, Naokazu; Aoyagi, Takao

2012-11-01

We proposed here a 'smart' control of an interface movement of proton diffusion in temperature- and pH-responsive hydrogels using a light-induced spatial pH-jump reaction. A photoinitiated proton-releasing reaction of o-nitrobenzaldehyde (NBA) was integrated into poly(N-isopropylacrylamide-o-2-carboxyisopropylacrylamide) (P(NIPAAm-co-CIPAAm)) hydrogels. NBA-integrated hydrogels demonstrated quick release of proton upon UV irradiation, allowing the pH inside the gel to decrease below the pK(a) of P(NIPAAm-co-CIPAAm) within a minute. The NBA-integrated gel was shown to shrink rapidly upon UV irradiation without polymer "skin layer" formation due to a uniform decrease of pH inside the gel. Spatial control of gel shrinking was also created by irradiating UV light to a limited region of the gel through a photomask. The interface of proton diffusion ("active interface") gradually moved toward non-illuminated area. The apparent position of "active interface", however, did not change remarkably above the LCST, while protons continuously diffused outward direction. This is because the "active interface" also moved inward direction as gel shrank above the LCST. As a result, slow movement of the apparent interface was observed. The NBA-integrated gel was also successfully employed for the controlled release of an entrapped dextran in a light controlled manner. This system is highly promising as smart platforms for triggered and programmed transportation of drugs. Copyright © 2011 Elsevier B.V. All rights reserved.

On/off-switchable LSPR nano-immunoassay for troponin-T

PubMed Central

Ashaduzzaman, Md.; Deshpande, Swapneel R.; Murugan, N. Arul; Mishra, Yogendra Kumar; Turner, Anthony P. F.; Tiwari, Ashutosh

2017-01-01

Regeneration of immunosensors is a longstanding challenge. We have developed a re-usable troponin-T (TnT) immunoassay based on localised surface plasmon resonance (LSPR) at gold nanorods (GNR). Thermosensitive poly(N-isopropylacrylamide) (PNIPAAM) was functionalised with anti-TnT to control the affinity interaction with TnT. The LSPR was extremely sensitive to the dielectric constant of the surrounding medium as modulated by antigen binding after 20 min incubation at 37 °C. Computational modelling incorporating molecular docking, molecular dynamics and free energy calculations was used to elucidate the interactions between the various subsystems namely, IgG-antibody (c.f., anti-TnT), PNIPAAM and/or TnT. This study demonstrates a remarkable temperature dependent immuno-interaction due to changes in the PNIPAAM secondary structures, i.e., globular and coil, at above or below the lower critical solution temperature (LCST). A series of concentrations of TnT were measured by correlating the λLSPR shift with relative changes in extinction intensity at the distinct plasmonic maximum (i.e., 832 nm). The magnitude of the red shift in λLSPR was nearly linear with increasing concentration of TnT, over the range 7.6 × 10−15 to 9.1 × 10−4 g/mL. The LSPR based nano-immunoassay could be simply regenerated by switching the polymer conformation and creating a gradient of microenvironments between the two states with a modest change in temperature. PMID:28382946

Preparation of thermo and pH-responsive polymer@Au/Fe3O4 core/shell nanoparticles as a carrier for delivery of anticancer agent

NASA Astrophysics Data System (ADS)

Ghorbani, Marjan; Hamishehkar, Hamed; Arsalani, Naser; Entezami, Ali Akbar

2015-07-01

In this work, a thermo and pH-responsive poly- N-isopropylacrylamide-co-itaconic acid containing thiol side groups were successfully synthesized to prepare Doxorubicin-loaded polymer@Au/Fe3O4 core/shell nanoparticles (DOX-NPs). Copolymer and NPs were fully characterized by FT-IR, HNMR, photo-correlation spectroscopy, SEM, X-ray diffraction, vibrating-sample magnetometer, thermal gravimetric analysis, and UV-Vis spectroscopy. The stimuli-responsive characteristics of NPs were evaluated by in vitro release study in simulated cancerous environment. The biocompatibility and cytotoxic properties of NPs and DOX-NPs are explored by MTT method. The prepared NPs with the size of 50 nm showed paramagnetic characteristics with suitable and stable dispersion at physiological medium and high loading capacity (up to 55 %) of DOX. DOX-NPs yielded a pH- and temperature-triggered release of entrapped drugs at tumor tissue environment (59 % of DOX release) compared to physiological condition (20 % of DOX release) during 48 h. In vitro cytotoxicity studies indicated that the NPs showed no cytotoxicity on A549 cells at different amounts after incubation for 72 h confirming its suitability as a drug carrier. DOX-NPs, on the other hand, caused an efficient anticancer performance as verified by MTT assay test. It was concluded that developed NPs by us in this study may open the possibilities for targeted delivery of DOX to the cancerous tissues.

Simultaneous measurement of the Young's modulus and the Poisson ratio of thin elastic layers.

PubMed

Gross, Wolfgang; Kress, Holger

2017-02-07

The behavior of cells and tissue is greatly influenced by the mechanical properties of their environment. For studies on the interactions between cells and soft matrices, especially those applying traction force microscopy the characterization of the mechanical properties of thin substrate layers is essential. Various techniques to measure the elastic modulus are available. Methods to accurately measure the Poisson ratio of such substrates are rare and often imply either a combination of multiple techniques or additional equipment which is not needed for the actual biological studies. Here we describe a novel technique to measure both parameters, the Youngs's modulus and the Poisson ratio in a single experiment. The technique requires only a standard inverted epifluorescence microscope. As a model system, we chose cross-linked polyacrylamide and poly-N-isopropylacrylamide hydrogels which are known to obey Hooke's law. We place millimeter-sized steel spheres on the substrates which indent the surface. The data are evaluated using a previously published model which takes finite thickness effects of the substrate layer into account. We demonstrate experimentally for the first time that the application of the model allows the simultaneous determination of both the Young's modulus and the Poisson ratio. Since the method is easy to adapt and comes without the need of special equipment, we envision the technique to become a standard tool for the characterization of substrates for a wide range of investigations of cell and tissue behavior in various mechanical environments as well as other samples, including biological materials.

Stable environmentally sensitive cationic hydrogels for controlled delivery applications.

PubMed

Deo, Namita; Ruetsch, S; Ramaprasad, K R; Kamath, Y

2010-01-01

New thermosensitive, cationic hydrogels were synthesized by the dispersion copolymerization of N-isopropylacrylamide (NIPAM) and (3-acrylamidopropyl)trimethylammonium chloride (AAPTAC). In the polymerization protocol, an amide-based comonomer, (3-acrylamidopropyl)trimethylammonium chloride, was reacted as a new alternative monomer for introducing positive charges into the thermosensitive hydrogel. The hydrogels were synthesized without making any pH adjustment in the aqueous medium. These hydrogel particles exhibited colloidal stability in the pH range of 1.5 to 11.0, while similar cationic hydrogels were reported to be unstable at pHs higher than 6. The stronger cationic character of the selected comonomer provided higher colloidal stability to the poly(NIPAM-co-AAPTAC) hydrogels. Furthermore, these hydrogels displayed sensitivity towards temperature, pH, and salt concentration. Interestingly, the particle size of hydrogels was found to be decreased significantly with an increase in temperature and salt concentration. In addition, using pyrene fluorescence spectroscopy, it was established that the hydrophobicity/hydrophilicity of the hydrogel particles was largely controlled by both pH and temperature. The thermosensitive hydrogels reported in this paper may be suitable for delivering different actives for cosmetic and medical applications. Although direct application of these hydrogel particles in cosmetics has not been shown at this stage, the methodology of making them and controlling their absorption and release properties as a function of temperature and pH has been demonstrated. Furthermore, these hydrogels may also have applications in scavenging organic and inorganic toxics.

Smart Hydrogel Particles: Biomarker Harvesting: One-step affinity purification, size exclusion, and protection against degradation

PubMed Central

Luchini, Alessandra; Geho, David H.; Bishop, Barney; Tran, Duy; Xia, Cassandra; Dufour, Robert; Jones, Clint; Espina, Virginia; Patanarut, Alexis; Zhu, Weidong; Ross, Mark; Tessitore, Alessandra; Petricoin, Emanuel; Liotta, Lance A.

2010-01-01

Disease-associated blood biomarkers exist in exceedingly low concentrations within complex mixtures of high-abundance proteins such as albumin. We have introduced an affinity bait molecule into N-isopropylacrylamide to produce a particle that will perform three independent functions within minutes, in one step, in solution: a) molecular size sieving b) affinity capture of all solution phase target molecules, and c) complete protection of harvested proteins from enzymatic degradation. The captured analytes can be readily electroeluted for analysis. PMID:18076201

Smart nanogels at the air/water interface: structural studies by neutron reflectivity

NASA Astrophysics Data System (ADS)

Zielińska, Katarzyna; Sun, Huihui; Campbell, Richard A.; Zarbakhsh, Ali; Resmini, Marina

2016-02-01

The development of effective transdermal drug delivery systems based on nanosized polymers requires a better understanding of the behaviour of such nanomaterials at interfaces. N-Isopropylacrylamide-based nanogels synthesized with different percentages of N,N'-methylenebisacrylamide as cross-linker, ranging from 10 to 30%, were characterized at physiological temperature at the air/water interface, using neutron reflectivity (NR), with isotopic contrast variation, and surface tension measurements; this allowed us to resolve the adsorbed amount and the volume fraction of nanogels at the interface. A large conformational change for the nanogels results in strong deformations at the interface. As the percentage of cross-linker incorporated in the nanogels becomes higher, more rigid matrices are obtained, although less deformed, and the amount of adsorbed nanogels is increased. The data provide the first experimental evidence of structural changes of nanogels as a function of the degree of cross-linking at the air/water interface.The development of effective transdermal drug delivery systems based on nanosized polymers requires a better understanding of the behaviour of such nanomaterials at interfaces. N-Isopropylacrylamide-based nanogels synthesized with different percentages of N,N'-methylenebisacrylamide as cross-linker, ranging from 10 to 30%, were characterized at physiological temperature at the air/water interface, using neutron reflectivity (NR), with isotopic contrast variation, and surface tension measurements; this allowed us to resolve the adsorbed amount and the volume fraction of nanogels at the interface. A large conformational change for the nanogels results in strong deformations at the interface. As the percentage of cross-linker incorporated in the nanogels becomes higher, more rigid matrices are obtained, although less deformed, and the amount of adsorbed nanogels is increased. The data provide the first experimental evidence of structural changes of nanogels as a function of the degree of cross-linking at the air/water interface. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07538f

Poly (N-ethyl aniline)/Ag Nanocomposite as Humidity Sensor

NASA Astrophysics Data System (ADS)

Pande, Nishigandh S.; Jaspal, Dipika; Ambekar, Jalindar

Poly (N-ethyl aniline)/Ag organic-inorganic composite has been synthesized by a single step in situ chemical oxidative polymerization method. The synthesis of Poly (N-ethyl aniline)/Ag nanocomposite has been confirmed by X-ray diffraction (XRD), Ultraviolet-Vis Spectroscopy (UV-visible), Fourier transform infrared analysis (FTIR) and FE-SEM investigations. XRD spectral study exhibited major diffraction in the range 20-80∘ (2θ) and indicated the semicrystalline nature of poly (N-ethyl aniline)/Ag nanocomposite. Characteristic peaks in UV-visible and FTIR spectra of poly (N-ethyl aniline) switched to higher wave numbers in poly (N-ethyl aniline)/Ag nanocomposite. Peaks at 1789cm-1, 1595cm-1, 667cm-1 and 501cm-1 in FTIR spectrum confirmed the formation of poly (N-ethyl aniline)/Ag nanocomposite. FE-SEM photographs reported agglomerated granular particulate nature of poly (N-ethyl aniline)/Ag nanocomposite. Synthesized poly (N-ethyl aniline)/Ag nanocomposite exhibited a high response to humidity, good reproducibility and stability at room temperature. An appreciable response was shown in the presence of 40% humid atmosphere for up to successive four cycles. Composite sensitivity has been found to increase with the increasing concentration of humidity, at room temperature.

Nanoscale functionalization and characterization of surfaces with hydrogel patterns and biomolecules

NASA Astrophysics Data System (ADS)

Dinakar, Hariharasudhan Chirra

The advent of numerous tools, ease of techniques, and concepts related to nanotechnology, in combination with functionalization via simple chemistry has made gold important for various biomedical applications. In this dissertation, the development and characterization of planar gold surfaces with responsive hydrogel patterns for rapid point of care sensing and the functionalization of gold nanoparticles for drug delivery are highlighted. Biomedical micro- and nanoscale devices that are spatially functionalized with intelligent hydrogels are typically fabricated using conventional UV-lithography. Herein, precise 3-D hydrogel patterns made up of temperature responsive crosslinked poly(N-isopropylacrylamide) over gold were synthesized. The XY control of the hydrogel was achieved using microcontact printing, while thickness control was achieved using atom transfer radical polymerization (ATRP). Atomic force microscopy analysis showed that to the ATRP reaction time governed the pattern growth. The temperature dependent swelling ratio was tailored by tuning the mesh size of the hydrogel. While nanopatterns exhibited a broad lower critical solution temperature (LCST) transition, surface roughness showed a sharp LCST transition. Quartz crystal microbalance with dissipation showed rapid response behavior of the thin films, which makes them applicable as functional components in biomedical devices. The easy synthesis, relative biocompatibility, inertness, and easy functionalization of gold nanoparticles (GNPs) have made them useful for various biomedical applications. Although ATRP can be successfully carried out over GNPs, the yield of stable solution based GNPs for biomedical applications prove to be low. As an alternative approach, a novel method of ISOlating, FUnctionalizing, and REleasing nanoparticles (ISOFURE) was proposed. Biodegradable poly(beta-amino ester) hydrogels were used to synthesize ISOFURE-GNP composites. ATRP was performed inside the composite, and the final hydrogel coated GNPs were released via matrix degradation. Response analysis confirmed that the ISOFURE method led to the increased stability and yield of the hydrogel coated ISOFURE-GNPs. The ISOFURE protocol was also utilized in functionalizing GNPs with enzyme catalase in the absence of a stabilizing reagent. Biotin-streptavidin affinity was used as the bioconjugation method. Activity analysis of the conjugated enzyme showed that the ISOFURE-GNPs showed enhanced biomolecular loading relative to solution based stabilizing reagent passivated GNPs. KEYWORDS: Hydrogel, Gold nanoparticle, ISOFURE, Atom transfer radical polymerization, Microcontact printing

A Mixed Stimuli-Responsive Magnetic and Gold Nanoparticle System for Rapid Purification, Enrichment, and Detection of Biomarkers

PubMed Central

Nash, Michael A.; Yager, Paul; Hoffman, Allan S.; Stayton, Patrick S.

2010-01-01

A new diagnostic system for the enrichment and detection of protein biomarkers from human plasma is presented. Gold nanoparticles (AuNPs) were surface-modified with a diblock copolymer synthesized using reversible addition fragmentation chain transfer (RAFT) polymerization. The diblock copolymer contained a thermally-responsive poly(N-isopropylacrylamide) (pNIPAAm) block, a cationic amine-containing block, and a semi-telechelic PEG2-biotin end group. When a mixed suspension of 23 nm pNIPAAm-modified AuNPs was heated with pNIPAAm-coated 10 nm iron oxide magnetic nanoparticles (mNPs) in human plasma, the thermally-responsive pNIPAAm directed the formation of mixed AuNP/mNP aggregates that could be separated efficiently with a magnet. Model studies showed that this mixed nanoparticle system could efficiently purify and strongly enrich the model biomarker protein streptavidin in spiked human plasma. A 10 ng/mL streptavidin sample was mixed with the biotinylated and pNIPAAm modified AuNP and magnetically separated in the mixed nanoparticle system with pNIPAAm mNPs. The aggregates were concentrated into a 50-fold smaller fluid volume at room temperature where the gold nanoparticle reagent redissolved with the streptavidin target still bound. The concentrated gold-labeled streptavidin could be subsequently analyzed directly using lateral flow immunochromatography. This rapid capture and enrichment module thus utilizes the mixed stimuli-responsive nanoparticle system to achieve direct concentration of a gold-labeled biomarker that can be directly analyzed using lateral flow or other rapid diagnostic strategies. PMID:21070026

Thermo/pH dual-stimuli-responsive drug delivery for chemo-/photothermal therapy monitored by cell imaging.

PubMed

Shu, Yang; Song, Rusheng; Zheng, Anqi; Huang, Jingli; Chen, Mingli; Wang, Jianhua

2018-05-01

A thermo/pH dual-stimuli-responsive drug delivery system (DDS) based on polymer coated mesoporous silica nanostructures (MSNs) is developed for facilitating chemotherapy and photothermal therapy. Thermo/pH-responsive polymer, poly((N-isopropylacrylamide, NIPAM)-co-methacrylic acid, MA), is grafted onto MSNs by in situ polymerization, followed by loading a chemotherapeutic drug (doxorubicin hydrochloride, DOX) and a near-infrared-absorbing phototherapeutic agent (indocyanine green, ICG) to construct the intelligent drug delivery system, shortly as DOX-ICG-MSN@p(NIPAM-co-MA). At NIR irradiation, the photothermal conversion capability of ICG raises the temperature of the DDS and opens the gatekeeper by shrinkage of the copolymer p(NIPAM-co-MA), which triggers controlled release of DOX at an elevated temperature. On the other hand, drug release is also realized at pH 5.3, a characteristic pH value in cancer cell microenvironment, at which it not only causes the shrinkage of the pH-sensitive polymeric moiety of methacrylic acid in MSN@p(NIPAM-co-MA) but also deteriorates electrostatic interaction of DOX molecules in the mesoporous channel by protonation of silanols. In addition, ICG further ensures photothermal therapy (PTT) and photodynamic therapy (PDT). The cytotoxicity assay of HeLa cells shows obvious synergistic effect by demonstrating that the combined use of DOX and ICG is more effective in killing HeLa cells than free DOX and ICG. The endocytosis of the drug is monitored by cell imaging. Copyright © 2018 Elsevier B.V. All rights reserved.

Influence of additives on thermoresponsive polymers in aqueous media: a case study of poly(N-isopropylacrylamide).

PubMed

Umapathi, Reddicherla; Reddy, P Madhusudhana; Rani, Anjeeta; Venkatesu, Pannuru

2018-04-18

Thermoresponsive polymers (TRPs) in different solvent media have been studied over a long period and are important from both scientific and technical points of view. Despite numerous studies on the behavior of TRPs with various additives, the interactions of additives with TRPs are still poorly understood. Moreover, despite the vast available literature regarding the biomolecular interactions between various TRPs and naturally occurring additives, it is not possible to provide a unifying declaration about the behavior of different additives, in particular at the phase transition temperature of the polymer. However, potential reviews that describe the behavior of additives as stimuli upon the phase transition of TRPs are also absent. A lack of sufficient knowledge regarding the responses of TRPs to additives as stimuli has hindered the expansion of the wide spectrum of applications of these polymers. Therefore, it was proposed to review the responses of TRPs in the presence of various additives in aqueous media. In-depth knowledge acquired via a literature survey has drawn our attention towards filling this gap by analyzing the interactions of TRPs with different additives. In this perspective, we have systematically examined the stability, aggregation, and phase transition behaviours of various polymers in the presence of different additives. The perspective on the influence of additives as stimuli on the behavior of TRPs in an aqueous medium will provide new reliable information about intramolecular interactions between interior polymer segments as well as intermolecular interactions between TRPs and additive molecules, which will be helpful for industrialists in the preparation of new polymeric materials for drug-delivery systems.

Microengineered 3D cell-laden thermoresponsive hydrogels for mimicking cell morphology and orientation in cartilage tissue engineering.

PubMed

Mellati, Amir; Fan, Chia-Ming; Tamayol, Ali; Annabi, Nasim; Dai, Sheng; Bi, Jingxiu; Jin, Bo; Xian, Cory; Khademhosseini, Ali; Zhang, Hu

2017-01-01

Mimicking the zonal organization of native articular cartilage, which is essential for proper tissue functions, has remained a challenge. In this study, a thermoresponsive copolymer of chitosan-g-poly(N-isopropylacrylamide) (CS-g-PNIPAAm) was synthesized as a carrier of mesenchymal stem cells (MSCs) to provide a support for their proliferation and differentiation. Microengineered three-dimensional (3D) cell-laden CS-g-PNIPAAm hydrogels with different microstripe widths were fabricated to control cellular alignment and elongation in order to mimic the superficial zone of natural cartilage. Biochemical assays showed six- and sevenfold increment in secretion of glycosaminoglycans (GAGs) and total collagen from MSCs encapsulated within the synthesized hydrogel after 28 days incubation in chondrogenic medium. Chondrogenic differentiation was also verified qualitatively by histological and immunohistochemical assessments. It was found that 75 ± 6% of cells encapsulated within 50 μm wide microstripes were aligned with an aspect ratio of 2.07 ± 0.16 at day 5, which was more organized than those observed in unpatterned constructs (12 ± 7% alignment and a shape index of 1.20 ± 0.07). The microengineered constructs mimicked the cell shape and organization in the superficial zone of cartilage whiles the unpatterned one resembled the middle zone. Our results suggest that microfabrication of 3D cell-laden thermosensitive hydrogels is a promising platform for creating biomimetic structures leading to more successful multi-zonal cartilage tissue engineering. Biotechnol. Bioeng. 2017;114: 217-231. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Fast Transport of Water Droplets over a Thermo-Switchable Surface Using Rewritable Wettability Gradient.

PubMed

Banuprasad, Theneyur Narayanaswamy; Vinay, Thamarasseril Vijayan; Subash, Cherumannil Karumuthil; Varghese, Soney; George, Sajan D; Varanakkottu, Subramanyan Namboodiri

2017-08-23

In spite of the reported temperature dependent tunability in wettability of poly(N-isopropylacrylamide) (PNIPAAm) surfaces for below and above lower critical solution temperature (32 °C), the transport of water droplets is inhibited by the large contact angle hysteresis. Herein, for the first time, we report on-demand, fast, and reconfigurable droplet manipulation over a PNIPAAm grafted structured polymer surface using temperature-induced wettability gradient. Our study reveals that the PNIPAAm grafted on intrinsically superhydrophobic surfaces exhibit hydrophilic nature with high contact angle hysteresis below 30 °C and superhydrophobic nature with ultralow contact angle hysteresis above 36 °C. The transition region between 30 and 36 °C is characterized by a large change in water contact angle (∼100°) with a concomitant change in contact angle hysteresis. By utilizing this "transport zone" wherein driving forces overcome the frictional forces, we demonstrate macroscopic transport of water drops with a maximum transport velocity of approximately 40 cm/s. The theoretical calculations on the force measurements concur with dominating behavior of driving forces across the transport zone. The tunability in transport velocity by varying the temperature gradient along the surface or the inclination angle of the surface (maximum angle of 15° with a reduced velocity 0.4 mm/s) is also elucidated. In addition, as a practical application, coalescence of water droplets is demonstrated by using the temperature controlled wettability gradient. The presented results are expected to provide new insights on the design and fabrication of smart multifunctional surfaces for applications such as biochemical analysis, self-cleaning, and microfluidics.

Dynamic Switching of Helical Microgel Ribbons.

PubMed

Zhang, Hang; Mourran, Ahmed; Möller, Martin

2017-03-08

We report on a microscopic poly(N-isopropylacrylamide) hydrogel ribbon, coated by a thin gold layer, that shows helical coiling. Confined swelling and shrinkage of the hydrogel below and above its characteristic volume phase transition leads to a temperature actuated reversal of the sense of the helix. The extent and the shape of the winding are controlled by the dimensions and mechanical properties of the bilayer ribbon. We focus on a cylindrical helix geometry and monitor the morphing under equilibrium and nonequilibrium conditions, that is, when the temperature changes faster than the volume (millisecond range). For slow temperature variations, the water release and uptake follow the equilibrium transition trajectory determined by the time needed for the diffusion of water into and out of the microscopic gel. Much faster variations of the temperature are accomplished by internal heating of embedded gold nanorods by IR-light irradiation. This causes elastic stresses that strongly affect the motions. This method enables well-reproducible deviations from the equilibrium transition path and allows us to control rather precisely the spatiotemporal transformation in a cyclic repetitive process. Actuation and response are sensitive to small variations of temperature and composition of the aqueous sol in which the gel is immersed. The principle as described may be used to detect specific analytes that bind either to the surface of the gold layer or within the gel and can modify the interaction between the water and the gel. The reported nonequilibrium morphing implies that the system dissipates energy and may also be able to perform work as required for a microscopic motor.

Thermodynamic Interactions between Polystyrene and Long-Chain Poly(n-Alkyl Acrylates) Derived from Plant Oils.

PubMed

Wang, Shu; Robertson, Megan L

2015-06-10

Vegetable oils and their fatty acids are promising sources for the derivation of polymers. Long-chain poly(n-alkyl acrylates) and poly(n-alkyl methacrylates) are readily derived from fatty acids through conversion of the carboxylic acid end-group to an acrylate or methacrylate group. The resulting polymers contain long alkyl side-chains with around 10-22 carbon atoms. Regardless of the monomer source, the presence of alkyl side-chains in poly(n-alkyl acrylates) and poly(n-alkyl methacrylates) provides a convenient mechanism for tuning their physical properties. The development of structured multicomponent materials, including block copolymers and blends, containing poly(n-alkyl acrylates) and poly(n-alkyl methacrylates) requires knowledge of the thermodynamic interactions governing their self-assembly, typically described by the Flory-Huggins interaction parameter χ. We have investigated the χ parameter between polystyrene and long-chain poly(n-alkyl acrylate) homopolymers and copolymers: specifically we have included poly(stearyl acrylate), poly(lauryl acrylate), and their random copolymers. Lauryl and stearyl acrylate were chosen as model alkyl acrylates derived from vegetable oils and have alkyl side-chain lengths of 12 and 18 carbon atoms, respectively. Polystyrene is included in this study as a model petroleum-sourced polymer, which has wide applicability in commercially relevant multicomponent polymeric materials. Two independent methods were employed to measure the χ parameter: cloud point measurements on binary blends and characterization of the order-disorder transition of triblock copolymers, which were in relatively good agreement with one another. The χ parameter was found to be independent of the alkyl side-chain length (n) for large values of n (i.e., n > 10). This behavior is in stark contrast to the n-dependence of the χ parameter predicted from solubility parameter theory. Our study complements prior work investigating the interactions between polystyrene and short-chain polyacrylates (n ≤ 10). To our knowledge, this is the first study to explore the thermodynamic interactions between polystyrene and long-chain poly(n-alkyl acrylates) with n > 10. This work lays the groundwork for the development of multicomponent structured systems (i.e., blends and copolymers) in this class of sustainable materials.

Probing the structural dependence of carbon space lengths of poly(N-hydroxyalkyl acrylamide)-based brushes on antifouling performance.

PubMed

Yang, Jintao; Zhang, Mingzhen; Chen, Hong; Chang, Yung; Chen, Zhan; Zheng, Jie

2014-08-11

Numerous biocompatible antifouling polymers have been developed for a wide variety of fundamental and practical applications in drug delivery, biosensors, marine coatings, and many other areas. Several antifouling mechanisms have been proposed, but the exact relationship among molecular structure, surface hydration property, and antifouling performance of antifouling polymers still remains elusive. Here this work strives to provide a better understanding of the structure-property relationship of poly(N-hydroxyalkyl acrylamide)-based materials. We have designed, synthesized, and characterized a series of polyHAAA brushes of various carbon spacer lengths (CSLs), that is, poly(N-hydroxymethyl acrylamide) (polyHMAA), poly(N-(2-hydroxyethyl)acrylamide) (polyHEAA), poly(N-(3-hydroxypropyl)acrylamide) (polyHPAA), and poly(N-(5-hydroxypentyl)acrylamide) (polyHPenAA), to study the structural dependence of CSLs on their antifouling performance. HMAA, HEAA, HPAA, and HPenAA monomers contained one, two, three, and five methylene groups between hydroxyl and amide groups, while the other groups in polymer backbones were the same as each other. The relation of such small structural differences of polymer brushes to their surface hydration and antifouling performance was studied by combined experimental and computational methods including surface plasmon resonance sensors, sum frequency generation (SFG) vibrational spectroscopy, cell adhesion assay, and molecular simulations. Antifouling results showed that all polyHAAA-based brushes were highly surface resistant to protein adsorption from single protein solutions, undiluted blood serum and plasma, as well as cell adhesion up to 7 days. In particular, polyHMAA and polyHEAA with the shorter CSLs exhibited higher surface hydration and better antifouling ability than polyHPMA and polyHPenAA. SFG and molecular simulations further revealed that the variation of CSLs changed the ratio of hydrophobicity/hydrophilicity of polymers, resulting in different hydration characteristics. Among them, polyHMAA and polyHEAA with the shorter CSLs showed the highest potency for surface hydration and antifouling abilities, while polyHPenAA showed the lowest potency. The combination of both hydroxyl and amide groups in the same polymer chain provides a promising structural motif for the design of new effective antifouling materials.

Interferon induction by and toxicity of polyriboinosinic acid [poly(rI)].polyribocytidylic acid [poly (rC)], mismatched analog poly (rI).poly[r(C12Uracil)n], and poly(rI).poly(rC) L-lysine complexed with carboxymethylcellulose.

PubMed Central

Stringfellow, D A; Weed, S D

1980-01-01

The ability of polyriboinosionic acid [poly(rI)].polyribocytidylic acid [poly(rC)], mismatched analog poly (rI).poly[r(C12Uracil)n], and poly(rI).poly(rC) complexed with poly L-lysine and carboxymethylcellulose [poly(ICLc)] to induce interferon and the comparative toxicity of each in cats were evaluated. Each induced high levels of circulating interferon, although poly(ICLC) injected intravenously at 1 to 4 mg/kg induced up to 10 times more interferon than the other compounds. Each compound was pyrogenic and caused a transient decrease in leukocyte numbers. Poly(rI).poly(rC) and the mismatched analog caused severe diarrhea and nausea at the highest drug concentrations (1 to 4 mg/kg), but poly (ICLC) did not. Each compound also caused depression and lethargy and impaired coordination. PMID:6157363

Self-oscillating AB diblock copolymer developed by post modification strategy

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

Ueki, Takeshi, E-mail: ueki@cross.t.u-tokyo.ac.jp, E-mail: ryo@cross.t.u-tokyo.ac.jp; Onoda, Michika; Tamate, Ryota

We prepared AB diblock copolymer composed of hydrophilic poly(ethylene oxide) segment and self-oscillating polymer segment. In the latter segment, ruthenium tris(2,2′-bipyridine) (Ru(bpy){sub 3}), a catalyst of the Belousov-Zhabotinsky reaction, is introduced into the polymer architecture based on N-isopropylacrylamide (NIPAAm). The Ru(bpy){sub 3} was introduced into the polymer segment by two methods; (i) direct random copolymerization (DP) of NIPAAm and Ru(bpy){sub 3} vinyl monomer and (ii) post modification (PM) of Ru(bpy){sub 3} with random copolymer of NIPAAm and N-3-aminopropylmethacrylamide. For both the diblock copolymers, a bistable temperature region (the temperature range; ΔT{sub m}), where the block copolymer self-assembles into micelle atmore » reduced Ru(bpy){sub 3}{sup 2+} state whereas it breaks-up into individual polymer chain at oxidized Ru(bpy){sub 3}{sup 3+} state, monotonically extends as the composition of the Ru(bpy){sub 3} increases. The ΔT{sub m} of the block copolymer prepared by PM is larger than that by DP. The difference in ΔT{sub m} is rationalized from the statistical analysis of the arrangement of the Ru(bpy){sub 3} moiety along the self-oscillating segments. By using the PM method, the well-defined AB diblock copolymer having ΔT{sub m} (ca. 25 °C) large enough to cause stable self-oscillation can be prepared. The periodic structural transition of the diblock copolymer in a dilute solution ([Polymer] = 0.1 wt. %) is closely investigated in terms of the time-resolved dynamic light scattering technique at constant temperature in the bistable region. A macroscopic viscosity oscillation of a concentrated polymer solution (15 wt. %) coupled with the periodic microphase separation is also demonstrated.« less

Chiral Structures of Thermoresponsive Soft Spheres in Hollow Cylinders

NASA Astrophysics Data System (ADS)

Lohr, Matthew A.; Alsayed, Ahmed; Zhang, Zexin; Yodh, Arjun G.

2009-03-01

We experimentally observe the formation of closely packed crystalline structures in hollow cylinders. The structures have varying degrees of chiral order. The systems are created from aqueous suspensions of thermoresponsive N-isopropylacrylamide (NIPA) microgel particles packed in micron-diameter glass capillaries. We categorize these structures according to classifications used by Erickson for tubular packings of hard spheres [1]. By varying the temperature-tunable diameter of these particles, the system's volume fraction is changed, permitting observations of the resilience of these structures and their melting transitions. Melting of these thermal crystalline structures is observed. [1] R. O. Erickson, Science 181 (1973) 705-716.

Surface Modification of Nanocellulose Substrates

NASA Astrophysics Data System (ADS)

Zoppe, Justin Orazio

Cellulose fibers constitute an important renewable raw material that is utilized in many commercial applications in non-food, paper, textiles and composite materials. Chemical functionalization is an important approach for improving the properties of cellulose based materials. Different approaches are used to graft polymeric chains onto cellulose substrates, which can be classified by two principal routes, namely 'grafting onto' or 'grafting from' methods. Never-dried cellulose nanocrystals (CNCs) or nanowhiskers produced from sulfuric acid hydrolysis of ramie fibers were used as substrates for surface chemical functionalization with various macromolecules. In addition, the use of cellulose nanocrystals to reinforce poly(epsilon-caprolactone) (PCL) nanofibers was studied. Chemical grafting with low molecular weight polycaprolactone diol onto cellulose nanocrystals was carried out in an attempt to improve the interfacial adhesion with the fiber matrix. Significant improvements in the mechanical properties of the nanofibers after reinforcement with unmodified cellulose nanocrystals were confirmed. Fiber webs from PCL reinforced with 2.5% unmodified CNCs showed ca. 1.5-fold increase in Young's modulus and ultimate strength compared to PCL webs. The CNCs were also grafted with poly(N-isopropylacrylamide) (poly(NiPAAm)) brushes via surface-initiated single-electron transfer living radical polymerization (SI-SETLRP) under various conditions at room temperature. The grafting process depended on the initiator and/or monomer concentrations used. No observable damage occurred to the CNCs after grafting, as determined by X-ray diffraction. Size exclusion chromatography analyses of polymer chains cleaved from the cellulose nanocrystals indicated that a higher degree of polymerization was achieved by increasing initiator or monomer loading, most likely caused by local heterogeneities yielding higher rates of polymerization. In addition, the colloidal stability and thermo-responsive behavior of poly(NiPAAm) brushes grafted from nanoparticles of CNCs of varying graft densities and molecular weights was investigated. Halo areas surrounding grafted CNCs that were adsorbed on silica and imaged with an AFM were indicative of the grafted polymer brushes. Aggregation of nanoparticles carrying grafts of high degree of polymerization was observed. The responsiveness of CNCs in liquid medium and as spin-coated films was determined by using light scattering, viscometry and Colloidal Probe Microscopy (CPM). Light transmittance measurements showed temperaturedependent aggregation originating from the different graft densities and molecular weights and a sharp increase in dispersion viscosity as the temperature approached the LCST. The lower critical solution temperature (LCST) of grafted poly(NiPAAm) brushes was found to decrease with the ionic strength as is the case of neat poly(NiPAAm) in aqueous solution. CPM in aqueous media for asymmetric systems consisting of thin films of CNCs and a colloidal silica probe showed the distinctive effects of the grafted polymer brushes on the interaction (repulsive and adhesive) forces. The origin of such forces was mainly electrostatic and steric in the case of bare and grafted CNCs, respectively. A decrease in the onset of attractive and adhesion forces of grafted CNCs films was observed with the ionic strength of the aqueous solution medium. The decreased mobility of polymer brushes upon partial collapse and decreased availability of hydrogen bonding sites with higher electrolyte concentration were hypothesized as main reasons for the less prominent polymer bridging between interacting surfaces. Finally, poly(NiPAAm)-g-CNCs were utilized as a Pickering emulsions stabilizer. All emulsions formed were oil-in-water confirmed by a drop test. Various drop sizes were obtained as characterized by laser scattering particle size analysis and optical microscopy. Anisotropic colloidal assemblies of grafted CNCs at the oil-water interface were observed in freeze-fractured samples via Transmission Electron Microscopy. Emulsions were stable for over three months at the time of writing this thesis, however rapidly broke above the LCST as determined by rheometry.

Deformation and fracture of cross-linked polymer gels

NASA Astrophysics Data System (ADS)

Lin, Wei-Chun

Because soft materials, particularly polymer gels, are playing a greater role in industrial and biotechnological applications today, the exploration of their mechanical behavior over a range of deformations is becoming more relevant in our daily lives. Understanding these properties is therefore necessary as a means to predict their response for specific applications. To address these concerns, this dissertation presents a set of analytic tools based on flat punch probe indentation tests to predict the response of polymer gels from a mechanical perspective over a large range of stresses and at failure. At small strains, a novel technique is developed to determine the transport properties of gels based on their measured mechanical behavior. Assuming that a polymer gel behaves in a similar manner as a porous structure, the differentiation of solvent flow from viscoelasticity of a gel network is shown to be possible utilizing a flat, circular punch and a flat, rectangular punch under oscillatory conditions. Use of the technique is demonstrated with a poly(N-isopropyl acrylamide) (pNIPAM) hydrogel. Our results indicate that solvent flow is inhibited at temperatures above the critical solution temperature of 35°C. At high stresses and fracture, the flat probe punch indentation geometry is used to understand how the structure and geometry of silicone based gels affect their mechanical properties. A delayed failure response of the gels is observed and the modes of failure are found to be dependent on the geometry of the system. The addition of a sol fraction in these gels was found to toughen the network and play an important role at these large deformations. Potential mechanisms of fracture resistance are discussed, as is the effect of geometric confinement as it relates to large scale deformation and fracture. These results lay the groundwork for understanding the mechanical response of other highly, deformable material systems utilizing this particular geometry.

Osmotically driven drug delivery through remote-controlled magnetic nanocomposite membranes.

PubMed

Zaher, A; Li, S; Wolf, K T; Pirmoradi, F N; Yassine, O; Lin, L; Khashab, N M; Kosel, J

2015-09-01

Implantable drug delivery systems can provide long-term reliability, controllability, and biocompatibility, and have been used in many applications, including cancer pain and non-malignant pain treatment. However, many of the available systems are limited to zero-order, inconsistent, or single burst event drug release. To address these limitations, we demonstrate prototypes of a remotely operated drug delivery device that offers controllability of drug release profiles, using osmotic pumping as a pressure source and magnetically triggered membranes as switchable on-demand valves. The membranes are made of either ethyl cellulose, or the proposed stronger cellulose acetate polymer, mixed with thermosensitive poly(N-isopropylacrylamide) hydrogel and superparamagnetic iron oxide particles. The prototype devices' drug diffusion rates are on the order of 0.5-2 μg/h for higher release rate designs, and 12-40 ng/h for lower release rates, with maximum release ratios of 4.2 and 3.2, respectively. The devices exhibit increased drug delivery rates with higher osmotic pumping rates or with magnetically increased membrane porosity. Furthermore, by vapor deposition of a cyanoacrylate layer, a drastic reduction of the drug delivery rate from micrograms down to tens of nanograms per hour is achieved. By utilizing magnetic membranes as the valve-control mechanism, triggered remotely by means of induction heating, the demonstrated drug delivery devices benefit from having the power source external to the system, eliminating the need for a battery. These designs multiply the potential approaches towards increasing the on-demand controllability and customizability of drug delivery profiles in the expanding field of implantable drug delivery systems, with the future possibility of remotely controlling the pressure source.

Osmotically driven drug delivery through remote-controlled magnetic nanocomposite membranes

PubMed Central

Zaher, A.; Li, S.; Wolf, K. T.; Pirmoradi, F. N.; Yassine, O.; Lin, L.; Khashab, N. M.; Kosel, J.

2015-01-01

Implantable drug delivery systems can provide long-term reliability, controllability, and biocompatibility, and have been used in many applications, including cancer pain and non-malignant pain treatment. However, many of the available systems are limited to zero-order, inconsistent, or single burst event drug release. To address these limitations, we demonstrate prototypes of a remotely operated drug delivery device that offers controllability of drug release profiles, using osmotic pumping as a pressure source and magnetically triggered membranes as switchable on-demand valves. The membranes are made of either ethyl cellulose, or the proposed stronger cellulose acetate polymer, mixed with thermosensitive poly(N-isopropylacrylamide) hydrogel and superparamagnetic iron oxide particles. The prototype devices' drug diffusion rates are on the order of 0.5–2 μg/h for higher release rate designs, and 12–40 ng/h for lower release rates, with maximum release ratios of 4.2 and 3.2, respectively. The devices exhibit increased drug delivery rates with higher osmotic pumping rates or with magnetically increased membrane porosity. Furthermore, by vapor deposition of a cyanoacrylate layer, a drastic reduction of the drug delivery rate from micrograms down to tens of nanograms per hour is achieved. By utilizing magnetic membranes as the valve-control mechanism, triggered remotely by means of induction heating, the demonstrated drug delivery devices benefit from having the power source external to the system, eliminating the need for a battery. These designs multiply the potential approaches towards increasing the on-demand controllability and customizability of drug delivery profiles in the expanding field of implantable drug delivery systems, with the future possibility of remotely controlling the pressure source. PMID:26487899

Effect of charge and molecular weight on the functionality of gelatin carriers for corneal endothelial cell therapy.

PubMed

Lai, Jui-Yang; Lu, Pei-Lin; Chen, Ko-Hua; Tabata, Yasuhiko; Hsiue, Ging-Ho

2006-06-01

Cell transplantation strategies usually involve the use of supporting carrier materials because of the soft and fragile nature of these grafts. In this work, a cell-adhesive gelatin hydrogel carrier was fabricated to deliver cultivated human corneal endothelial cell (HCEC) sheets, which were harvested from thermo-responsive poly(N-isopropylacrylamide) (PNIPAAm)-grafted culture surfaces. The carrier disks, consisting of gelatins with a different isoelectric point (IEP = 5.0 and 9.0) and a molecular weight (MW) ranging from 3 to 100 kDa, were subjected to 16.6 kGy gamma irradiation for sterilization. The effect of IEP and MW of the raw gelatins (i.e., before irradiation) on the functionality of sterilized disks was studied by determinations of mechanical property, water content, dissolution degree, and cytocompatibility. Irrespective of the IEP of raw gelatin, hydrogel disks prepared with high MW (100 kDa) exhibited a greater tensile strength, lower water content, and slower dissolution rate than those made of low MW gelatin (8 and 3 kDa). From the investigation of cellular responses to the disks, the negatively charged gelatin (IEP = 5.0) groups were more cytocompatible when compared with their positively charged counterparts (IEP = 9.0) at the same MW (100 kDa). Additionally, in the negatively charged gelatin groups, only a slight increase in pro-inflammatory cytokine expression was observed with increasing MW of gelatin from 3 to 100 kDa. It is concluded that the gamma-sterilized hydrogel disks made from raw gelatins (IEP = 5.0, MW = 100 kDa) with appropriate dissolution degree and acceptable cytocompatibility are capable of providing stable mechanical support, making these carriers promising candidates for intraocular delivery of cultivated HCEC sheets.

Simulation of controllable permeation in PNIPAAm coated membranes

NASA Astrophysics Data System (ADS)

Ehrenhofer, Adrian; Wallmersperger, Thomas; Richter, Andreas

2016-04-01

Membranes separate fluid compartments and can comprise transport structures for selective permeation. In biology, channel proteins are specialized in their atomic structure to allow transport of specific compounds (selectivity). Conformational changes in protein structure allow the control of the permeation abilities by outer stimuli (gating). In polymeric membranes, the selectivity is due to electrostatic or size-exclusion. It can thus be controlled by size variation or electric charges. Controllable permeation can be useful to determine particle-size distributions in continuous flow, e.g. in microfluidics and biomedicine to gain cell diameter profiles in blood. The present approach uses patterned polyethylene terephthalate (PET) membranes with hydrogel surface coating for permeation control by size-exclusion. The thermosensitive hydrogel poly(N-isopropylacrylamide) (PNIPAAm) is structured with a cross-shaped pore geometry. A change in the temperature of the water flow through the membrane leads to a pore shape variation. The temperature dependent behavior of PNIPAAm can be numerically modeled with a temperature expansion model, where the swelling and deswelling is depicted by temperature dependent expansion coefficients. In the present study, the free swelling behavior was implemented to the Finite Element tool ABAQUS for the complex composite structure of the permeation control membrane. Experimental values of the geometry characteristics were derived from microscopy images with the tool Image J and compared to simulation results. Numerical simulations using the derived thermo-mechanical model for different pore geometries (circular, rectangle, cross and triangle) were performed. With this study, we show that the temperature expansion model with values from the free swelling behavior can be used to adequately predict the deformation behavior of the complex membrane system. The predictions can be used to optimize the behavior of the membrane pores and the overall performance of the smart membrane.

Synthesis of fast response crosslinked PVA-g-NIPAAm nanohydrogels by very low radiation dose in dilute aqueous solution

NASA Astrophysics Data System (ADS)

Fathi, Marziyeh; Reza Farajollahi, Ali; Akbar Entezami, Ali

2013-05-01

Nanohydrogels of poly(vinyl alcohol)-g-N-isopropylacrylamide (PVA-g-NIPAAm) are synthesized by PVA and NIPAAm dilute aqueous solution using much less radiation dose of 1-20 Gy via intramolecular crosslinking at ambient temperature. The radiation synthesis of nanohydrogels is performed in the presence of tetrakis (hydroxymethyl) phosphonium chloride (THPC) due to its rapid oxygen scavenging abilities and hydrogen peroxide (H2O2) as a source of hydroxyl radicals. The effect of radiation dose, feed composition ratio of PVA and H2O2 is investigated on swelling properties such as temperature and pH dependence of equilibrium swelling ratio as well as deswelling kinetics. Experimental data exhibit high equilibrium swelling ratio and fast response time for the synthesized nanohydrogels. The average molecular weight between crosslinks (Mc) and crosslinking density (ρx) of the obtained nanohydrogels are calculated from swelling data as a function of radiation dose, H2O2 and PVA amount. Fourier transform infrared spectroscopy (FT-IR), elemental analysis of nitrogen content and thermogravimetric analysis (TGA) are used to confirm the grafting reaction. Lower critical solution temperature (LCST) is measured around 33 °C by differential scanning calorimetry (DSC) for PVA-g-NIPAAm nanohydrogels. Dynamic light scattering (DLS) data demonstrate that the increase of radiation dose leads to the decreasing in dimension of nanohydrogels. Also, rheological studies are confirmed an improvement in the mechanical properties of the nanohydrogels with increasing the radiation dose. A cytotoxicity study exhibits a good biocompatibility for the obtained nanohydrogels. The prepared nanohydrogels show fast swelling/deswelling behavior, high swelling ratio, dual sensitivity and good cytocompatibility, which may find potential applications as biomaterial.

Embedment of silver into temperature- and pH-responsive microgel for the development of smart textiles with simultaneous moisture management and controlled antimicrobial activities.

PubMed

Štular, Danaja; Jerman, Ivan; Naglič, Iztok; Simončič, Barbara; Tomšič, Brigita

2017-03-01

Silver nanoparticles were embedded into a temperature- and pH-responsive microgel based on poly-(N-isopropylacrylamide) and chitosan (PNCS) before or after its application to cotton fabric to create a smart stimuli-responsive textile with simultaneous moisture management and controlled antimicrobial activities. Two different methods of silver embedment into the PNCS microgel using two different forms of silver nanoparticles were studied, i.e., in-situ synthesis of AgCl nanocrystals into PNCS microgel particles that had previously been applied to cotton fabric, as well as the direct incorporation of colloidal silver into the microgel suspension prior to its deposition on cellulose fibres. SEM and FT-IR analysis were employed to determine the morphological and chemical changes of the modified cotton fibres, while EDS and ICP MS analysis were used to confirm the presence of the silver nanoparticles. The influence of silver embedment on the swelling/deswelling activity of the PNCS microgel was studied using the temperature- and pH-responsiveness, as determined by the moisture content, water vapour transmission rate and water uptake. The antimicrobial activity against the bacteria Staphylococcus aureus and Escherichia coli was assessed. Regardless of the embedment technique, the presence of silver nanoparticles resulted in impaired moisture management activity of the studied microgel. The PNCS microgel proved to be a suitable carrier of antimicrobial agents, assuring the effective controlled release of silver triggered by changes in the temperature and pH of the surroundings, which granted the cotton fabric excellent antimicrobial activity against Gram-negative E. coli (>99%) and Gram-positive S. aureus (>85%). Copyright © 2016 Elsevier Ltd. All rights reserved.

On the importance of Bloom number of gelatin to the development of biodegradable in situ gelling copolymers for intracameral drug delivery.

PubMed

Chou, Shih-Feng; Luo, Li-Jyuan; Lai, Jui-Yang; Ma, David Hui-Kang

2016-09-10

To overcome the drawbacks associated with conventional antiglaucoma eye drops, this work demonstrated the feasibility of an effective alternative strategy to administer pilocarpine directly via intracameral injections of drug-containing biodegradable in situ gelling GN copolymers composed of gelatin and poly(N-isopropylacrylamide). Specifically, this study aims to understand the importance of Bloom number of gelatin, a physicochemical parameter, to the development of GN carriers for intracameral drug delivery in glaucoma therapy. Our results showed that both imino acid and triple-helix contents increased with increasing Bloom index from 75-100 to 300. The drug encapsulation efficiency in response to temperature-triggered phase transition in GN copolymers was affected by the Bloom index of gelatin. In addition, the differences in protein secondary structure significantly influenced the degradation rates of GN carriers, which were highly correlated with drug release profiles. The increase in released pilocarpine concentration led to a high intracellular calcium level in rabbit ciliary smooth muscle cell cultures, indicating a beneficial pharmacological response to a drug. Irrespective of Bloom number of gelatin, all carrier materials exhibited excellent in vitro and in vivo biocompatibility with corneal endothelium. In a glaucomatous rabbit model, intracameral injections of pilocarpine-containing GN synthesized from gelatins with various Bloom numbers had different abilities to improve ocular hypertension and induce pupillary constriction, indicating distinct antiglaucoma efficacies due to in vivo drug release. It is concluded that the effects on pharmacological treatment using GN carriers for intracameral pilocarpine administration demonstrate a strong dependence on the Bloom number of gelatin. Copyright © 2016 Elsevier B.V. All rights reserved.

A Cooperative Copper Metal-Organic Framework-Hydrogel System Improves Wound Healing in Diabetes.

PubMed

Xiao, Jisheng; Chen, Siyu; Yi, Ji; Zhang, Hao; Ameer, Guillermo A

2017-01-05

Chronic non-healing wounds remain a major clinical challenge that would benefit from the development of advanced, regenerative dressings that promote wound closure within a clinically relevant time frame. The use of copper ions has shown promise in wound healing applications possibly by promoting angiogenesis. However, reported treatments that use copper ions require multiple applications of copper salts or oxides to the wound bed, exposing the patient to potentially toxic levels of copper ions and resulting in variable outcomes. Herein we set out to assess whether copper metal organic framework nanoparticles (HKUST-1 NPs) embedded within an antioxidant thermoresponsive citrate-based hydrogel would decrease copper ion toxicity and accelerate wound healing in diabetic mice. HKUST-1 and poly-(polyethyleneglycol citrate-co- N -isopropylacrylamide) (PPCN) were synthesized and characterized. HKUST-1 NP stability in a protein solution with and without embedding them in PPCN hydrogel was determined. Copper ion release, cytotoxicity, apoptosis, and in vitro migration processes were measured. Wound closure rates and wound blood perfusion were assessed in vivo using the splinted excisional dermal wound diabetic mouse model. HKUST-1 NP disintegrated in protein solution while HKUST-1 NPs embedded in PPCN (H-HKUST-1) were protected from degradation and copper ions were slowly released. Cytotoxicity and apoptosis due to copper ion release were significantly reduced while dermal cell migration in vitro and wound closure rates in vivo were significantly enhanced. In vivo , H-HKUST-1 induced angiogenesis, collagen deposition, and re-epithelialization during wound healing in diabetic mice. These results suggest that a cooperatively stabilized, copper ion-releasing H-HKUST-1 hydrogel is a promising innovative dressing for the treatment of chronic wounds.

A simple route to synthesize conductive stimuli-responsive polypyrrole nanocomposite hydrogel particles with strong magnetic properties and their performance for removal of hexavalent chromium ions from aqueous solution

NASA Astrophysics Data System (ADS)

Ahmad, Hasan; Rahman, Mohammad Mostafizar; Ali, Mohammad Azgar; Minami, Hideto; Tauer, Klaus; Gafur, Mohammad Abdul; Rahman, Mohammad Mahbubor

2016-08-01

A combination of maghemite polypyrrole (PPy/γ-Fe2O3) and stimuli-responsive properties in the same hydrogel microspheres is expected to enhance their application potential in various fields such as tissue engineering, regenerative medicine, biosensors, biomedical applications and removal of heavy metals from waste water, catalysis etc. In this investigation a simple two step process is used to prepare conductive stimuli-responsive polypyrrole (PPy) composite hydrogel particles with strong magnetic properties. Poly(styrene-methacrylic acid-N-isopropylacrylamide-polyethelene glycol methacrylate) or P(S-NIPAM-MAA-PEGMA) hydrogel seed particles are first prepared by soap-free precipitation copolymerization. The copolymer hydrogel particles exhibited both temperature- and pH-responsive volume phase transition. Conductive P(S-NIPAM-MAA-PEGMA)/PPy/γ-Fe2O3 nanocomposite hydrogel particles are then prepared by seeded chemical oxidative polymerization of pyrrole in the presence of P(S-NIPAM-MAA-PEGMA) hydrogel seed particles using FeCl3 as a oxidant and p-toluene sulfonic acid (p-TSA) as a dopant. In the reaction system FeCl3 functioned as a source of Fe(III) for the formation of γ-Fe2O3. This reaction also requires the initial presence of Fe(II) provided by the addition of FeCl2. The size and size distribution, surface structure, and morphology of the prepared conductive composite hydrogel particles are confirmed by FTIR, electron micrographs, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and UV-visible spectroscopy. The performance of nanocomposite hydrogel particles has been evaluated for the removal of hexavalent chromium (Cr) ions from water.

A Comparative Study of Natural Antimicrobial Delivery Systems for Microbial Safety and Quality of Fresh-Cut Lettuce.

PubMed

Hill, Laura E; Oliveira, Daniela A; Hills, Katherine; Giacobassi, Cassie; Johnson, Jecori; Summerlin, Harvey; Taylor, T Matthew; Gomes, Carmen L

2017-05-01

Nanoencapsulation can provide a means to effectively deliver antimicrobial compounds and enhance the safety of fresh produce. However, to date there are no studies which directly compares how different nanoencapsulation systems affect fresh produce safety and quality. This study compared the effects on quality and safety of fresh-cut lettuce treated with free and nanoencapsulated natural antimicrobial, cinnamon bark extract (CBE). A challenge study compared antimicrobial efficacy of 3 different nanoencapsulated CBE systems. The most effective antimicrobial treatment against Listeria monocytogenes was chitosan-co-poly-N-isopropylacrylamide (chitosan-PNIPAAM) encapsulated CBE, with a reduction on bacterial load up to 2 log 10 CFU/g (P < 0.05) compared to the other encapsulation systems when fresh-cut lettuce was stored at 5 °C and 10 °C for 15 d. Subsequently, chitosan-PNIPAAM-CBE nanoparticles (20, 40, and 80 mg/mL) were compared to a control and free CBE (400, 800, and 1600 μg/mL) for its effects on fresh-cut lettuce quality over 15 d at 5 °C. By the 10th day, the most effective antimicrobial concentration was 80 mg/mL for chitosan-PNIPAAM-CBE, up to 2 log 10 CFU/g reduction (P < 0.05), compared with the other treatments. There was no significant difference between control and treated samples up to day 10 for the quality attributes evaluated. Chitosan-PNIPAAM-CBE nanoparticles effectively inhibited spoilage microorganisms' growth and extended fresh-cut lettuce shelf-life. Overall, nanoencapsulation provided a method to effectively deliver essential oil and enhanced produce safety, while creating little to no detrimental quality changes on the fresh-cut lettuce. © 2017 Institute of Food Technologists®.

Sustained release of stromal cell derived factor-1 from an antioxidant thermoresponsive hydrogel enhances dermal wound healing in diabetes.

PubMed

Zhu, Yunxiao; Hoshi, Ryan; Chen, Siyu; Yi, Ji; Duan, Chongwen; Galiano, Robert D; Zhang, Hao F; Ameer, Guillermo A

2016-09-28

Diabetic foot ulcers (DFUs) are a severe complication of diabetes mellitus. Altered cell migration due to microcirculatory deficiencies as well as excessive and prolonged reactive oxygen species production are implicated in the delayed healing of DFUs. The goal of this research was to assess whether sustained release of SDF-1, a chemokine that promotes endothelial progenitor cell homing and angiogenesis, from a citrate-based antioxidant thermoresponsive polymer would significantly improve impaired dermal wound healing in diabetes. Poly (polyethylene glycol citrate-co-N-isopropylacrylamide) (PPCN) was synthesized via sequential polycondensation and free radical polymerization reactions. SDF-1 was entrapped via gelation of the PPCN+SDF-1 solution above its lower critical solution temperature (LCST) and its release and bioactivity was measured. The effect of sustained release of SDF-1 from PPCN (PPCN+SDF-1) versus a bolus application of SDF-1 in phosphate buffered saline (PBS) on wound healing was evaluated in a diabetic murine splinted excisional dermal wound model using gross observation, histology, immunohistochemistry, and optical coherence tomography microangiography. Increasing PPCN concentration decreased SDF-1 release rate. The time to 50% wound closure was 11days, 16days, 14days, and 17days for wounds treated with PPCN+SDF-1, SDF-1 only, PPCN only, and PBS, respectively. Wounds treated with PPCN+SDF-1 had the shortest time for complete healing (24days) and exhibited accelerated granulation tissue production, epithelial maturation, and the highest density of perfused blood vessels. In conclusion, sustained release of SDF-1 from PPCN is a promising and easy to use therapeutic strategy to improve the treatment of chronic non-healing DFUs. Copyright © 2016 Elsevier B.V. All rights reserved.

Augmentation of poly(ADP-ribose) polymerase-dependent neuronal cell death by acidosis.

PubMed

Zhang, Jian; Li, Xiaoling; Kwansa, Herman; Kim, Yun Tai; Yi, Liye; Hong, Gina; Andrabi, Shaida A; Dawson, Valina L; Dawson, Ted M; Koehler, Raymond C; Yang, Zeng-Jin

2017-06-01

Tissue acidosis is a key component of cerebral ischemic injury, but its influence on cell death signaling pathways is not well defined. One such pathway is parthanatos, in which oxidative damage to DNA results in activation of poly(ADP-ribose) polymerase and generation of poly(ADP-ribose) polymers that trigger release of mitochondrial apoptosis-inducing factor. In primary neuronal cultures, we first investigated whether acidosis per sé is capable of augmenting parthanatos signaling initiated pharmacologically with the DNA alkylating agent, N-methyl- N'-nitro- N-nitrosoguanidine. Exposure of neurons to medium at pH 6.2 for 4 h after N-methyl- N'-nitro- N-nitrosoguanidine washout increased intracellular calcium and augmented the N-methyl- N'-nitro- N-nitrosoguanidine-evoked increase in poly(ADP-ribose) polymers, nuclear apoptosis-inducing factor , and cell death. The augmented nuclear apoptosis-inducing factor and cell death were blocked by the acid-sensitive ion channel-1a inhibitor, psalmotoxin. In vivo, acute hyperglycemia during transient focal cerebral ischemia augmented tissue acidosis, poly(ADP-ribose) polymers formation, and nuclear apoptosis-inducing factor , which was attenuated by a poly(ADP-ribose) polymerase inhibitor. Infarct volume from hyperglycemic ischemia was decreased in poly(ADP-ribose) polymerase 1-null mice. Collectively, these results demonstrate that acidosis can directly amplify neuronal parthanatos in the absence of ischemia through acid-sensitive ion channel-1a . The results further support parthanatos as one of the mechanisms by which ischemia-associated tissue acidosis augments cell death.

PREPARATION OF BLOCK COPOLYMERS OF POLY(STYRENE) AND POLY(T-BUTYL ACRYLATE) OF VARIOUS MOLECULAR WEIGHTS AND ARCHITECTURES BY ATOM TRANSFER RADICAL POLYMERIZATION. (R826735)

EPA Science Inventory

Block copolymers of polystyrene and poly(t-butyl acrylate) were prepared using atom transfer radical polymerization techniques. These polymers were synthesized with a CuBr/N,N,N,NElectrically atomised formulations of timolol maleate for direct and on-demand ocular lens coatings.

PubMed

Mehta, Prina; Al-Kinani, Ali A; Haj-Ahmad, Rita; Arshad, Muhammad Sohail; Chang, Ming-Wei; Alany, Raid G; Ahmad, Zeeshan

2017-10-01

Advances in nanotechnology have enabled solutions for challenging drug delivery targets. While the eye presents numerous emerging opportunities for delivery, analysis and sensing; issues persist for conventional applications. This includes liquid phase formulation localisation on the ocular surface once administered as formulated eye-drops; with the vast majority of dosage (>90%) escaping from the administered site due to tear production and various drainage mechanisms. The work presented here demonstrates a single needle electrohydrodynamic (EHD) engineering process to nano-coat (as an on demand and controllable fiber depositing method) the surface of multiple contact lenses rendering formulations to be stationary on the lens and at the bio-interface. The coating process was operational based on ejected droplet charge and glaucoma drug timolol maleate (TM) was used to demonstrate surface coating optimisation, bio-surface permeation properties (flux, using a bovine model) and various kinetic models thereafter. Polymers PVP, PNIPAM and PVP:PNIPAM (50:50%w/w) were used to encapsulate the active. Nano-fibrous and particulate samples were characterised using SEM, FTIR, DSC and TGA to confirm structural and thermal stability of surface coated formulations. More than 52% of nano-structured coatings (for all formulations) were <200nm in diameter. In vitro studies show coatings to exhibit biphasic release profiles; an initial burst release followed by sustained release; with TM-loaded PNIPAM coating releasing most drug after 24h (89.8%). Kinetic modelling (Higuchi, Korsmeyer-Peppas) was indicative of quasi-Fickian diffusion whilst biological evaluation demonstrates adequate ocular tolerability. Results from permeation studies indicate coated lenses are ideal to reduce dosing regimen, which in turn will reduce systemic drug absorption. Florescent microscopy demonstrated probe and probe embedded coating behaviour from lens surface in vitro. The multiple lens surface coating method demonstrates sustained drug release yielding promising results; suggesting both novel device and method to enhance drug activity at the eyes surface which will reduce formulation drainage. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Effects of carbon-to-sulfur (C/S) ratio and nitrate (N) dosage on Denitrifying Sulfur cycle-associated Enhanced Biological Phosphorus Removal (DS-EBPR)

PubMed Central

Yu, Mei; Lu, Hui; Wu, Di; Zhao, Qing; Meng, Fangang; Wang, Yudan; Hao, Xiaodi; Chen, Guang-Hao

2016-01-01

In this study, the Denitrifying Sulfur cycle-associated Enhanced Biological Phosphorous Removal (DS-EBPR) with 20 mg P/L/d of the volumetric P removal rate was successfully achieved in a Sequencing Batch Reactor (SBR). The effects of carbon-to-sulfur (C/S) mass ratio and nitrate (N) dosage were investigated through two batch tests to reveal the role of wastewater compositions in DS-EBPR performance. The optimal specific P release and uptake rates (0.4 and 2.4 mg P/g VSS/h, respectively) were achieved at C/S/P/N mass ratio of 150/200/20/20, and poly-S is supplied as a potential electron and energy storage. The nitrate dosage in a range of 10–50 mg N/L had no significant influence on P uptake rates (2.1 ~ 2.4 mg P/g VSS/h), but significantly affected the storage of inclusion poly-S, the poly-S oxidation rate was increased about 16% while dosing nitrate from 20 to 30 mg N/L. It implies that nitrate is denitrified in the P uptake phase, and excess nitrate is further consumed by poly-S. Moreover, the microbial analysis showed that the functional bacteria should mostly belong to denitrifying bacteria or Unclassified genera. PMID:26983801

Tuning the Protein Corona of Hydrogel Nanoparticles: The Synthesis of Abiotic Protein and Peptide Affinity Reagents.

PubMed

O'Brien, Jeffrey; Shea, Kenneth J

2016-06-21

Nanomaterials, when introduced into a complex, protein-rich environment, rapidly acquire a protein corona. The type and amount of proteins that constitute the corona depend significantly on the synthetic identity of the nanomaterial. For example, hydrogel nanoparticles (NPs) such as poly(N-isopropylacrylamide) (NIPAm) have little affinity for plasma proteins; in contrast, carboxylated poly(styrene) NPs acquire a dense protein corona. This range of protein adsorption suggests that the protein corona might be "tuned" by controlling the chemical composition of the NP. In this Account, we demonstrate that small libraries of synthetic polymer NPs incorporating a diverse pool of functional monomers can be screened for candidates with high affinity and selectivity to targeted biomacromolecules. Through directed synthetic evolution of NP compositions, one can tailor the protein corona to create synthetic organic hydrogel polymer NPs with high affinity and specificity to peptide toxins, enzymes, and other functional proteins, as well as to specific domains of large proteins. In addition, many NIPAm NPs undergo a change in morphology as a function of temperature. This transformation often correlates with a significant change in NP-biomacromolecule affinity, resulting in a temperature-dependent protein corona. This temperature dependence has been used to develop NP hydrogels with autonomous affinity switching for the protection of proteins from thermal stress and as a method of biomacromolecule purification through a selective thermally induced catch and release. In addition to temperature, changes in pH or buffer can also alter a NP protein corona composition, a property that has been exploited for protein purification. Finally, synthetic polymer nanoparticles with low nanomolar affinity for a peptide toxin were shown to capture and neutralize the toxin in the bloodstream of living mice. While the development of synthetic polymer alternatives to protein affinity reagents is in its early stages, these recent successes using only small libraries of functional monomers are most encouraging. It is likely that by expanding the chemical diversity of functional hydrogels and other polymers, a much broader range of NP-biomacromolecule affinity pairs will result. Since these robust, nontoxic polymers are readily synthesized in the chemistry laboratory, we believe the results presented in this Account offer a promising future for the development of low cost alternatives to more traditional protein affinity reagents such as antibodies.

Development and characterization of targeted poly(NIPAm) nanoparticles for delivery of anti-inflammatory peptides in peripheral artery disease and osteoarthritis

NASA Astrophysics Data System (ADS)

McMasters, James F.

Inflammation is the underlying cause of several severe diseases including cardiovascular disease and osteoarthritis. Peripheral artery disease (PAD) is characterized by atherosclerotic occlusions within the peripheral vasculature. Current treatment for severe PAD involves mechanical widening of the artery via percutaneous transluminal angioplasty. Unfortunately, deployment of the balloon damages the endothelial layer, exposing the underlying collagenous matrix. Circulating platelets can bind to this collagen and become activated, releasing proinflammatory cytokines that promote proliferation of local smooth muscle cells. These proliferating cells eventually reocclude the vessel, resulting in restenosis and necessitating the need for a second procedure to reopen the vessel. Current treatments for moderate osteoarthritis include local injection of anti-inflammatory compounds such as glucocorticoids. Unfortunately, prolonged treatment carries with it significant side effects including osteoporosis, and cardiovascular complications. Our lab has developed an anti-inflammatory cell-penetrating peptide that inhibits mitogen-activated protein kinase activated protein kinase 2 (MK2). MK2 is implicated in the inflammatory cascade of atherosclerosis and osteoarthritis, making it a potentially effective strategy for reducing inflammation in both disease states. Unfortunately, these peptides are untargeted and quickly degraded in the presence of serum proteases, making the development of an effective delivery system of paramount importance. The overall goal of the research presented here is to detail the development of a poly(N-isopropylacrylamide) nanoparticle that is able to effectively load and release anti-inflammatory peptides for the treatment of these inflammatory diseases. In this dissertation, I will discuss the development of a collagen-binding nanoparticle that is able to inhibit platelet binding following angioplasty, thereby halting the initial inflammatory cascade. Additionally, these particles demonstrate the ability to reduce inflammation by through the loading and release of MK2-inhibiting cell-penetrating peptides. Additionally, I will cover the development of a hollow nanoparticle system that is designed to load increased quantities of these anti-inflammatory peptides for the treatment of osteoarthritis. This particle demonstrated increased macrophage uptake and prolonged drug release, resulting in a progressive inhibition of osteoarthritic inflammation over 8 days. The results presented here advance our understanding of these nanoparticle platforms, and suggest that they may serve at effective platforms for the treatment of restenosis following angioplasty, as well as osteoarthritis.

Synthesis of Poly[APMA]-DOTA-64Cu conjugates for interventional radionuclide therapy of prostate cancer: assessment of intratumoral retention by micro-positron emission tomography.

PubMed

Yuan, Jianchao; You, Yezi; Lu, Xin; Muzik, Otto; Oupicky, David; Peng, Fangyu

2007-01-01

To develop new radiopharmaceuticals for interventional radionuclide therapy of locally recurrent prostate cancer, poly[N-(3-aminopropyl)methacrylamide] [poly(APMA)] polymers were synthesized by free radical precipitation polymerization in acetone-dimethylsulfoxide using N,N'-azobis(isobutyronitrile) as the initiator. The polymers were characterized with nuclear magnetic resonance, size exclusion chromatography, and dynamic light scattering (M(n) = 2.40 x 10(4), M(w)/M(n) = 1.87). Subsequently, poly[APMA] was coupled with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride as an activator, followed by conjugation with (64)Cu radionuclide. Prolonged retention of poly[APMA]-DOTA-(64)Cu conjugates within the tumor tissues was demonstrated by micro-positron emission tomography at 24 hours following intra-tumoral injection of the conjugates to human prostate xenografts in mice. The data suggest that the poly[APMA]-DOTA-(64)Cu conjugates might be useful for interventional radionuclide therapy of locally recurrent prostate cancer in humans.

Influence of the transition region between p- and n-type polycrystalline silicon passivating contacts on the performance of interdigitated back contact silicon solar cells

NASA Astrophysics Data System (ADS)

Reichel, Christian; Müller, Ralph; Feldmann, Frank; Richter, Armin; Hermle, Martin; Glunz, Stefan W.

2017-11-01

Passivating contacts based on thin tunneling oxides (SiOx) and n- and p-type semi-crystalline or polycrystalline silicon (poly-Si) enable high passivation quality and low contact resistivity, but the integration of these p+/n emitter and n+/n back surface field junctions into interdigitated back contact silicon solar cells poses a challenge due to high recombination at the transition region from p-type to n-type poly-Si. Here, the transition region was created in different configurations—(a) p+ and n+ poly-Si regions are in direct contact with each other ("pn-junction"), using a local overcompensation (counterdoping) as a self-aligning process, (b) undoped (intrinsic) poly-Si remains between the p+ and n+ poly-Si regions ("pin-junction"), and (c) etched trenches separate the p+ and n+ poly-Si regions ("trench")—in order to investigate the recombination characteristics and the reverse breakdown behavior of these solar cells. Illumination- and injection-dependent quasi-steady state photoluminescence (suns-PL) and open-circuit voltage (suns-Voc) measurements revealed that non-ideal recombination in the space charge regions with high local ideality factors as well as recombination in shunted regions strongly limited the performance of solar cells without a trench. In contrast, solar cells with a trench allowed for open-circuit voltage (Voc) of 720 mV, fill factor of 79.6%, short-circuit current (Jsc) of 41.3 mA/cm2, and a conversion efficiencies (η) of 23.7%, showing that a lowly conducting and highly passivating intermediate layer between the p+ and n+ poly-Si regions is mandatory. Independent of the configuration, no hysteresis was observed upon multiple stresses in reverse direction, indicating a controlled and homogeneously distributed breakdown, but with different breakdown characteristics.

Triblock copolyampholytes from 5-(N,N-dimethyl amino)isoprene styrene, and methacrylic acid: Synthesis and solution properties

NASA Astrophysics Data System (ADS)

Bieringer, R.; Abetz, V.; Müller, A. H. E.

ABC triblock copolymers of the type poly[5-(N,N-dimethyl amino)isoprene]-block-polystyrene-block-poly(tert-butyl methacrylate) (AiST) were synthesized and hydrolyzed to yield poly[5-(N,N-dimethyl amino)isoprene]-block-polystyrene-block-poly(methacrylic acid) (AiSA) triblock copolyampholytes. Due to a complex solubility behavior the solution properties of these materials had to be investigated in THF/water solvent mixtures. Potentiometric titrations of AiSA triblock copolyampholytes showed two inflection points with the A block being deprotonated prior to the Ai hydrochloride block thus forming a polyzwitterion at the isoelectric point (iep). The aggregation behavior was studied by dynamic light scattering (DLS) and freeze-fracture/transmission electron microscopy (TEM). Large vesicular structures with almost pH-independent radii were observed.

Toxic PRn poly-dipeptides encoded by the C9orf72 repeat expansion block nuclear import and export.

PubMed

Shi, Kevin Y; Mori, Eiichiro; Nizami, Zehra F; Lin, Yi; Kato, Masato; Xiang, Siheng; Wu, Leeju C; Ding, Ming; Yu, Yonghao; Gall, Joseph G; McKnight, Steven L

2017-02-14

The toxic proline:arginine (PR n ) poly-dipeptide encoded by the (GGGGCC) n repeat expansion in the C9orf72 form of heritable amyotrophic lateral sclerosis (ALS) binds to the central channel of the nuclear pore and inhibits the movement of macromolecules into and out of the nucleus. The PR n poly-dipeptide binds to polymeric forms of the phenylalanine:glycine (FG) repeat domain, which is shared by several proteins of the nuclear pore complex, including those in the central channel. A method of chemical footprinting was used to characterize labile, cross-β polymers formed from the FG domain of the Nup54 protein. Mutations within the footprinted region of Nup54 polymers blocked both polymerization and binding by the PR n poly-dipeptide. The aliphatic alcohol 1,6-hexanediol melted FG domain polymers in vitro and reversed PR n -mediated enhancement of the nuclear pore permeability barrier. These data suggest that toxicity of the PR n poly-dipeptide results in part from its ability to lock the FG repeats of nuclear pore proteins in the polymerized state. Our study offers a mechanistic interpretation of PR n poly-dipeptide toxicity in the context of a prominent form of ALS.

Integrated system for temperature-controlled fast protein liquid chromatography comprising improved copolymer modified beaded agarose adsorbents and a travelling cooling zone reactor arrangement.

PubMed

Müller, Tobias K H; Cao, Ping; Ewert, Stephanie; Wohlgemuth, Jonas; Liu, Haiyang; Willett, Thomas C; Theodosiou, Eirini; Thomas, Owen R T; Franzreb, Matthias

2013-04-12

An integrated approach to temperature-controlled chromatography, involving copolymer modified agarose adsorbents and a novel travelling cooling zone reactor (TCZR) arrangement, is described. Sepharose CL6B was transformed into a thermoresponsive cation exchange adsorbent (thermoCEX) in four synthetic steps: (i) epichlorohydrin activation; (ii) amine capping; (iii) 4,4'-azobis(4-cyanovaleric acid) immobilization; and 'graft from' polymerization of poly(N-isopropylacrylamide-co-N-tert-butylacrylamide-co-acrylic acid-co-N,N'-methylenebisacrylamide). FT-IR, (1)H NMR, gravimetry and chemical assays allowed precise determination of the adsorbent's copolymer composition and loading, and identified the initial epoxy activation step as a critical determinant of 'on-support' copolymer loading, and in turn, protein binding performance. In batch binding studies with lactoferrin, thermoCEX's binding affinity and maximum adsorption capacity rose smoothly with temperature increase from 20 to 50 °C. In temperature shifting chromatography experiments employing thermoCEX in thermally jacketed columns, 44-51% of the lactoferrin adsorbed at 42 °C could be desorbed under binding conditions by cooling the column to 22 °C, but the elution peaks exhibited strong tailing. To more fully exploit the potential of thermoresponsive chromatography adsorbents, a new column arrangement, the TCZR, was developed. In TCZR chromatography, a narrow discrete cooling zone (special assembly of copper blocks and Peltier elements) is moved along a bespoke fixed-bed separation columnfilled with stationary phase. In tests with thermoCEX, it was possible to recover 65% of the lactoferrin bound at 35 °C using 8 successive movements of the cooling zone at a velocity of 0.1mm/s; over half of the recovered protein was eluted in the first peak in more concentrated form than in the feed. Intra-particle diffusion of desorbed protein out of the support pores, and the ratio between the velocities of the cooling zone and mobile phase were identified as the main parameters affecting TCZR performance. In contrast to conventional systems, which rely on cooling the whole column to effect elution and permit only batch-wise operation, TCZR chromatography generates sharp concentrated elution peaks without tailing effects and appears ideally suited for continuous operation. Copyright © 2013 Elsevier B.V. All rights reserved.

Heterologous Expression, Purification and Immunoreactivity of the Antigen 5 from Polybia paulista Wasp Venom

PubMed Central

Bazon, Murilo Luiz; Perez-Riverol, Amilcar; dos Santos-Pinto, José Roberto Aparecido; Lasa, Alexis Musacchio; Justo-Jacomini, Débora Laís; Palma, Mario Sergio

2017-01-01

Polybia paulista (Hymenoptera: Vespidae) is responsible for a high number of sting accidents and anaphylaxis events in Southeast Brazil, Argentina and Paraguay. The specific detection of allergy to the venom of this wasp is often hampered by the lack of recombinant allergens currently available for molecular diagnosis. Antigen 5 (~23 kDa) from P. paulista venom (Poly p 5) is a highly abundant and glycosylated allergenic protein that could be used for development of component-resolved diagnosis (CRD). Here, we describe the cloning and heterologous expression of the antigen 5 (rPoly p 5) from P. paulista venom using the eukaryotic system Pichia pastoris. The expression as a secreted protein yielded high levels of soluble rPoly p 5. The recombinant allergen was further purified to homogeneity (99%) using a two-step chromatographic procedure. Simultaneously, the native form of the allergen (nPoly p 5) was purified from the wasp venom by Ion exchange chromatography. The rPoly p 5 and nPoly p 5 were then submitted to a comparative analysis of IgE-mediated immunodetection using sera from patients previously diagnosed with sensitization to wasp venoms. Both rPoly p 5 and nPoly p 5 were recognized by specific IgE (sIgE) in the sera of the allergic individuals. The high levels of identity found between nPoly p 5 and rPoly p 5 by the alignment of its primary sequences as well as by 3-D models support the results obtained in the immunoblot. Overall, we showed that P. pastoris is a suitable system for production of soluble rPoly p 5 and that the recombinant allergen represents a potential candidate for molecular diagnosis of P.paulista venom allergy. PMID:28837089

Delivery of phytochemical thymoquinone using molecular micelle modified poly(D, L lactide-co-glycolide) (PLGA) nanoparticles

NASA Astrophysics Data System (ADS)

Ganea, Gabriela M.; Fakayode, Sayo O.; Losso, Jack N.; van Nostrum, Cornelus F.; Sabliov, Cristina M.; Warner, Isiah M.

2010-07-01

Continuous efforts have been made in the development of potent benzoquinone-based anticancer drugs aiming for improved water solubility and reduced adverse reactions. Thymoquinone is a liposoluble benzoquinone-based phytochemical that has been shown to have remarkable antioxidant and anticancer activities. In the study reported here, thymoquinone-loaded PLGA nanoparticles were synthesized and evaluated for physico-chemical, antioxidant and anticancer properties. The nanoparticles were synthesized by an emulsion solvent evaporation method using anionic molecular micelles as emulsifiers. The system was optimized for maximum entrapment efficiency using a Box-Behnken experimental design. Optimum conditions were found for 100 mg PLGA, 15 mg TQ and 0.5% w/v poly(sodium N-undecylenyl-glycinate) (poly-SUG). In addition, other structurally related molecular micelles such as poly(sodium N-heptenyl-glycinate) (poly-SHG), poly(sodium N-undecylenyl-leucinate) (poly-SUL), and poly(sodium N-undecylenyl-valinate) (poly-SUV) were also examined as emulsifiers. All investigated molecular micelles provided excellent emulsifier properties, leading to maximum optimized TQ entrapment efficiency, and monodispersed particle sizes below 200 nm. The release of TQ from molecular micelle modified nanoparticles was investigated by dialysis and reached lower levels than the free drug. The antioxidant activity of TQ-loaded nanoparticles, indicated by IC50 (mg ml - 1 TQ for 50% 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity), was highest for poly-SUV emulsified nanoparticles (0.030 ± 0.002 mg ml - 1) as compared to free TQ. In addition, it was observed that TQ-loaded nanoparticles emulsified with poly-SUV were more effective than free TQ against MDA-MB-231 cancer cell growth inhibition, presenting a cell viability of 16.0 ± 5.6% after 96 h.

In vitro adhesion and biocompatability of osteoblast-like cells to poly(methylmethacrylate) and poly(ethylmethacrylate) bone cements.

PubMed

Dalby, M J; Di Silvio, L; Harper, E J; Bonfield, W

2002-03-01

A bone cement, poly(ethylmethacrylate)/n-butylmethacrylate (PEMA/nBMA) has been developed with lower exotherm and monomer leaching compared to the traditional poly(methylmethacrylate)/methylmethacrylate (PMMA/MMA) cement. This study compares the in vitro biological response to the cements using primary human osteoblast-like cells (HOB). Cell attachment was qualified by immunolocalization of vinculin and actin cytoskeleton, showing more organization on PEMA/nBMA compared to PMMA/MMA. Proliferation was assessed using tritiated thymidine incorporation, and phenotype expression determined by measuring alkaline phosphatase (ALP) activity. An increase in proliferation and ALP activity was observed on PEMA/nBMA compared to PMMA/MMA. The results confirm the biocompatability of PEMA/nBMA, and an enhanced cell attachment and expression of differentiated cell phenotype.

Poly(ornithine-co-arginine-co-glycine-co-aspartic Acid): Preparation via NCA Polymerization and its Potential as a Polymeric Tumor-Penetrating Agent.

PubMed

Yu, Haiyang; Tang, Zhaohui; Zhang, Dawei; Song, Wantong; Duan, Taicheng; Gu, Jingkai; Chen, Xuesi

2015-06-01

A novel random copolypeptide of ornithine, arginine, glycine, and aspartic acid [Poly(ornithine-co-arginine-co-glycine-co-aspartic acid), Poly(O,R,G,D)] has been prepared through ring-opening polymerization of N-δ-carbobenzoxy-l-ornithine N-carboxyanhydride [Orn(Cbz)-NCA)], l-glycine N-carboxyanhydride (Gly-NCA) and β-benzyl l-aspartate N-carboxyanhydride [Asp(Bn)-NCA], following by subsequent deprotection and guanidization. The structure of Poly(O,R,G,D) was confirmed by nuclear magnetic resonance (NMR) spectroscopy and gel permeation chromatography (GPC). Low cytotoxicity of Poly(O,R,G,D) was confirmed from MTT assay. The Poly(O,R,G,D) contain some internal sequences of RXXR (X = O, R, G, or D) that could be proteolytically cleaved to expose the cryptic CendR element and bind to Neuropilin-1. This would lead to vascular and tissue permeabilization. Therefore trypsin-cleaved Poly(O,R,G,D) increase the vascular leakage of Evans blue from dermal microvessels at the injection site in vivo skin permeability assay. The intratumoral injection of the Poly(O,R,G,D) significantly enhanced the concentration of cisplatin-loaded nanoparticles in MCF-7 solid tumors. These results show that Poly(O,R,G,D) could increase the vascular leakage and tissue penetration of nanoparticles in a solid tumor and can be used as a potential polymeric tumor-penetrating agent. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polymer–Metal–Organic Frameworks (polyMOFs) as Water Tolerant Materials for Selective Carbon Dioxide Separations

DOE PAGES

Zhang, Zhenjie; Nguyen, Ha Thi Hoang; Miller, Stephen A.; ...

2015-12-28

Recently, polymer–metal–organic frameworks (polyMOFs) were reported as a new class of hybrid porous materials that combine advantages of both organic polymers and crystalline MOFs. Herein, we report a bridging coligand strategy to prepare new types of polyMOFs, demonstrating that polyMOFs are compatible with additional MOF architectures besides that of the earlier reported IRMOF-1 type polyMOF. Gas sorption studies revealed that these polyMOF materials exhibited relatively high CO 2 sorption but very low N 2 sorption, making them promising materials for CO 2/N 2 separations. Furthermore, these polyMOFs demonstrated exceptional water stability attributed to the hydrophobicity of polymer ligands as wellmore » as the cross-linking of the polymer chains within the MOF.« less

Triple helical polynucleotidic structures: an FTIR study of the C+ .G. Ctriplet.

PubMed

Akhebat, A; Dagneaux, C; Liquier, J; Taillandier, E

1992-12-01

Triple helixes containing one homopurine poly dG or poly rG strand and two homopyrimidine poly dC or poly rC strands have been prepared and studied by FTIR spectroscopy in H2O and D2O solutions. The spectra are discussed by comparison with those of the corresponding third strands (auto associated or not) and of double stranded poly dG.poly dC and poly rG.poly rC in the same concentration range and salt conditions. The triplex formation is characterized by the study of the base-base interactions reflected by changes in the spectral domain involving the in-plane double bond vibrations of the bases. Modifications of the initial duplex conformation (A family form for poly rG.poly rC, B family form for poly dG.poly dC) when the triplex is formed have been investigated. Two spectral domains (950-800 and 1450-1350 cm-1) containing absorption bands markers of the N and S type sugar geometries have been extensively studied. The spectra of the triplexes prepared starting with a double helix containing only riboses (poly rC+.poly rG.poly rC and poly dC+.poly rG.poly rC) as well as that of poly rC+.poly dG.poly dC present exclusively markers of the North type geometry of the sugars. On the contrary in the case of the poly dC+.poly dG.poly dC triplex both N and S type sugars are shown to coexist. The FTIR spectra allow us to propose that in this case the sugars of the purine (poly dG) strand adopt the S type geometry.

Thermally Switchable Thin Films of an ABC Triblock Copolymer of Poly(n-butyl methacrylate)-poly(methyl methacrylate)-poly(2-fluoroethyl methacrylate)

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

Zhang, Shanju; Liu, Zhan; Bucknall, David G.

2011-01-01

The thermo-responsive behavior of polymer films consisting of novel linear triblock copolymers of poly(n-butyl methacrylate)-poly(methyl methacrylate)-poly(2-fluoroethyl methacrylate) (PnBuMA-PMMA-P2FEMA) are reported using differential scanning calorimetry (DSC), atomic forcing microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and contacting angle (CA) measurements. The surface morphology, wettability and chemical structure of thin films of these triblock copolymers on silicon wafers as a function of temperature have been investigated. It has been shown that the wettability of the films is thermally switchable. Detailed structural analysis shows that thermo-responsive surface composition changes are produced. The underlying mechanism of the thermoresponsive behavior is discussed.

A Cell-Targeted Non-Cytotoxic Fluorescent Nanogel Thermometer Created with an Imidazolium-Containing Cationic Radical Initiator.

PubMed

Uchiyama, Seiichi; Tsuji, Toshikazu; Kawamoto, Kyoko; Okano, Kentaro; Fukatsu, Eiko; Noro, Takahiro; Ikado, Kumiko; Yamada, Sayuri; Shibata, Yuka; Hayashi, Teruyuki; Inada, Noriko; Kato, Masaru; Koizumi, Hideki; Tokuyama, Hidetoshi

2018-05-04

A cationic fluorescent nanogel thermometer based on thermo-responsive N-isopropylacrylamide and environment-sensitive benzothiadiazole was developed with a new azo compound bearing imidazolium rings as the first cationic radical initiator. This cationic fluorescent nanogel thermometer showed an excellent ability to enter live mammalian cells in a short incubation period (10 min), a high sensitivity to temperature variations in live cells (temperature resolution of 0.02-0.84 °C in the range 20-40 °C), and remarkable non-cytotoxicity, which permitted ordinary cell proliferation and even differentiation of primary cultured cells. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Specific interactions study in complexes of poly(mono-n-alkyl itaconates) with tertiary polyamides.

PubMed

Katime, Issa; Meaurio, Emilio; Cesteros, Luis C; Mendizábal, Eduardo

2003-07-01

This paper reports an FT-IR study of blends of poly(mono-n-alkyl itaconates) with poly(N,N-dimethylacrylamide) (PDMA) and poly(ethyloxazoline) (PEOX). Strong hydrogen bonding has been found, and both polybases have shown similar acceptor strengths. Derivative techniques show asymmetric profiles for the free carbonyl band of the polybases, resulting in shifted band locations. The extent of the interassociation has been estimated by spectral curve fitting of the polybase carbonyl band. The results show that the interaction degree in blends with PEOX does not depend on the length of the poly(monoalkyl itaconate) side group, while an inter-associating ability loss is observed in blends with PDMA as the side-group size of the polyacid increases. This different behavior is attributed to the greater interspacing between vicinal carbonyl groups in PEOX. This band shows conformational sensitivity and reflects the conformational changes that occur as the steric hindrances present in the medium (due to the bulky side groups of the polyacids) increase.

Biomimetic honeycomb-patterned surface as the tunable cell adhesion scaffold.

PubMed

Chen, Shuangshuang; Lu, Xuemin; Hu, Ying; Lu, Qinghua

2015-01-01

Inspired by the typically adhesive behaviors of fish skin and Parthenocissus tricuspidata, two different decorations of polystyrene honeycomb membrane (PSHCM) prepared by the breath figure approach were carried out with poly(N-(3-Sulfopropyl)-N-(methacryloxyethyl)-N,N-dimethylammonium betaine)(polySBMA) to explore controllable bioadhesive surfaces. Casting and dip-coating were employed to graft polySBMA onto the plasma treated PSHCM. The polySBMA casted PSHCM showed a uniform covering layer on the PSHCM similar to the mucus layer of fish skin, presenting excellent antifouling properties. On the contrary, a dip-coated one showed the polySBMA aggregating on the honeycomb pore walls forming a large number of sucking disks such as the adhesive disks of the tendrils of P. tricuspidata, which remarkably boosts cell adhesion on substrates. Thus, bioadhesion could be regulated as desired by tuning the distribution of zwitterionic polymer on the honeycomb surface. The results may provide a new approach for the design of biomaterial surfaces.

Poly(DL-lactide)-b-poly(N,N-dimethylamino-2-ethyl methacrylate): synthesis, characterization, micellization behavior in aqueous solutions, and encapsulation of the hydrophobic drug dipyridamole.

PubMed

Karanikolopoulos, Nikos; Zamurovic, Miljana; Pitsikalis, Marinos; Hadjichristidis, Nikos

2010-02-08

We synthesized a series of well-defined poly(dl-lactide)-b-poly(N,N-dimethylamino-2-ethyl methacrylate) (PDLLA-b-PDMAEMA) amphiphilic diblock copolymers by employing a three-step procedure: (a) ring-opening polymerization (ROP) of dl-lactide using n-decanol and stannous octoate, Sn(Oct)(2), as the initiating system, (b) reaction of the PDLLA hydroxyl end groups with bromoisobutyryl bromide, and (c) atom transfer radical polymerization, ATRP, of DMAEMA with the newly created bromoisobutyryl initiating site. The aggregation behavior of the prepared block copolymers was investigated by dynamic light scattering and zeta potential measurements at 25 degrees C in aqueous solutions of different pH values. The hydrophobic drug dipyridamole was efficiently incorporated into the copolymer aggregates in aqueous solutions of pH 7.40. High partition coefficient values were determined by fluorescence spectroscopy.

Quartz crystal microbalance with coupled spectroscopic ellipsometry-study of temperature-responsive polymer brush systems

NASA Astrophysics Data System (ADS)

Adam, Stefan; Koenig, Meike; Rodenhausen, Keith Brian; Eichhorn, Klaus-Jochen; Oertel, Ulrich; Schubert, Mathias; Stamm, Manfred; Uhlmann, Petra

2017-11-01

Using a combined setup of quartz crystal microbalance with dissipation monitoring together with spectroscopic ellipsometry, the thermo-responsive behavior of two different brush systems (poly(N-isopropyl acrylamide) and poly(2-oxazoline)s) was investigated and compared to the behavior of the free polymer in solution. Poly(2-oxazoline)s with three different hydrophilicities were prepared by changing the content of a hydrophilic comonomer. While both polymer types exhibit a sharp, discontinuous thermal transition in solution, in the brush state the transition gets broader in the case of poly(N-isopropyl acrylamide) and is transformed into a continuous transition for poly(2-oxazoline)s. The position of the transition in solution is influenced by the degree of hydrophilicity of the poly(2-oxazoline). The difference in areal mass detected by quartz crystal microbalance and by spectroscopic ellipsometry, has been attributed to the chain segment density profile of the polymer brushes. Applying this density profile information, for poly(N-isopropyl acrylamide) two different swelling stages could be identified, while for poly(2-oxazoline) the transition between a parabolic and more step-wise profile is found continuous. The different swelling characteristics were attributed to the different miscibility behavior types, with the brush state acting similar to a crosslinked system.

New structures and composition of cell wall teichoic acids from Nocardiopsis synnemataformans, Nocardiopsis halotolerans, Nocardiopsis composta and Nocardiopsis metallicus: a chemotaxonomic value.

PubMed

Tul'skaya, Elena M; Shashkov, Alexander S; Streshinskaya, Galina M; Potekhina, Natalia V; Evtushenko, Ludmila I

2014-12-01

The structures of the cell wall teichoic acids (TA) from some species of the genus Nocardiopsis were established by chemical and NMR spectroscopic methods. The cell walls of Nocardiopsis synnemataformans VKM Ac-2518(T) and Nocardiopsis halotolerans VKM Ac-2519(T) both contain two TA with unique structures-poly(polyol phosphate-glycosylpolyol phosphate)-belonging to the type IV TA. In both organisms, the minor TA have identical structures: poly(glycerol phosphate-N-acetyl-β-galactosaminylglycerol phosphate) with the phosphodiester bond between C-3 of glycerol and C-4 of the amino sugar. This structure is found for the first time. The major TA of N. halotolerans has a hitherto unknown structure: poly(glycerol phosphate-N-acetyl-β-galactosaminylglycerol phosphate), the N-acetyl-β-galactosamine being acetalated with pyruvic acid at positions 4 and 6. The major TA of N. synnemataformans is a poly(glycerol phosphate-N-acetyl-β-galactosaminylglycerol phosphate) with the phosphodiester bond between C-3 of glycerol and C-3 of the amino sugar. The cell walls of Nocardiopsis composta VKM Ac-2520 and N. composta VKM Ac-2521(T) contain only one TA, namely 1,3-poly(glycerol phosphate) partially substituted with N-acetyl-α-glucosamine. The cell wall of Nocardiopsis metallicus VKM Ac-2522(T) contains two TA. The major TA is 1,5-poly(ribitol phosphate), each ribitol unit carrying a pyruvate ketal group at positions 2 and 4. The structure of the minor TA is the same as that of N. composta. The results presented correlate well with the phylogenetic grouping of strains and confirm the species and strain specific features of cell wall TA in members of the genus Nocardiopsis.

Elastin Based Cell-laden Injectable Hydrogels with Tunable Gelation, Mechanical and Biodegradation Properties

PubMed Central

Fathi, Ali; Mithieux, Suzanne M.; Wei, Hua; Chrzanowski, Wojciech; Valtchev, Peter; Weiss, Anthony S.; Dehghani, Fariba

2015-01-01

Injectable hydrogels made from extracellular matrix proteins such as elastin show great promise for various biomedical applications. Use of cytotoxic reagents, fixed gelling behavior, and lack of mechanical strength in these hydrogels are the main associated drawbacks. The aim of this study was to develop highly cytocompatible and injectable elastin-based hydrogels with alterable gelation characteristics, favorable mechanical properties and structural stability for load bearing applications. A thermoresponsive copolymer, poly(N-isopropylacrylamide-co-polylactide-2-hydroxyethyl methacrylate-co-oligo(ethylene glycol)monomethyl ether methacrylate, was functionalized with succinimide ester groups by incorporating N-acryloxysuccinimide monomer. These ester groups were exploited to covalently bond this polymer, denoted as PNPHO, to different proteins with primary amine groups such as α-elastin in aqueous media. The incorporation of elastin through covalent bond formation with PNPHO promotes the structural stability, mechanical properties and live cell proliferation within the structure of hydrogels. Our results demonstrated that elastin-co-PNPHO solutions were injectable through fine gauge needles and converted to hydrogels in situ at 37 °C in the absence of any crosslinking reagent. By altering PNPHO content, the gelling time of these hydrogels can be finely tuned within the range of 2 to 15 min to ensure compatibility with surgical requirements. In addition, these hydrogels exhibited compression moduli in the range of 40 to 145 kPa, which are substantially higher than those of previously developed elastin-based hydrogels. These hydrogels were highly stable in the physiological environment with the evidence of 10 wt% mass loss in 30 days of incubation in a simulated environment. This class of hydrogels is in vivo bioabsorbable due to the gradual increase of the lower critical solution temperature of the copolymer to above 37 °C due to the cleavage of polylactide from the PNPHO copolymer. Moreover, our results demonstrated that more than 80% of cells encapsulated in these hydrogels remained viable, and the number of encapsulated cells increased for at least 5 days. These unique properties mark elastin-co-PNHPO hydrogels as favorable candidates for a broad range of tissue engineering applications. PMID:24731705

Gd@C82 metallofullerenes for neutron capture therapy—fullerene solubilization by poly(ethylene glycol)-block-poly(2-(N, N-diethylamino)ethyl methacrylate) and resultant efficacy in vitro

PubMed Central

Horiguchi, Yukichi; Kudo, Shinpei; Nagasaki, Yukio

2011-01-01

Poly(ethylene glycol)-block-poly(2-(N,N-diethylamino)ethyl methacrylate) (PEG-b-PAMA) was found to solubilize fullerenes such as C60, and this technique was applied to metallofullerenes. Gd@C82 was easily dissolved in water in the presence of PEG-b-PAMA without any covalent derivatization, forming a transparent complex about 20–30 nm in diameter. Low cytotoxicity was confirmed in vitro. Neutron irradiation of cultured cells (colon-26 adenocarcinoma) with Gd@C82-PEG-b-PAMA-complexed nanoparticles showed effective cytotoxicity, indicating the effective emission of gamma rays and internal conversion electrons produced from the neutron capture reaction of Gd. This result suggests a potentially valuable approach to gadolinium-based neutron capture therapy. PMID:27877415

A Copolymer Scaffold Functionalized with Nanodiamond Particles Enhances Osteogenic Metabolic Activity and Bone Regeneration.

PubMed

Yassin, Mohammed A; Mustafa, Kamal; Xing, Zhe; Sun, Yang; Fasmer, Kristine Eldevik; Waag, Thilo; Krueger, Anke; Steinmüller-Nethl, Doris; Finne-Wistrand, Anna; Leknes, Knut N

2017-06-01

Functionalizing polymer scaffolds with nanodiamond particles (nDPs) has pronounced effect on the surface properties, such as improved wettability, an increased active area and binding sites for cellular attachment and adhesion, and increased ability to immobilize biomolecules by physical adsorption. This study aims to evaluate the effect of poly(l-lactide-co-ε-caprolactone) (poly(LLA-co-CL)) scaffolds, functionalized with nDPs, on bone regeneration in a rat calvarial critical size defect. Poly(LLA-co-CL) scaffolds functionalized with nDPs are also compared with pristine scaffolds with reference to albumin adsorption and seeding efficiency of bone marrow stromal cells (BMSCs). Compared with pristine scaffolds, the experimental scaffolds exhibit a reduction in albumin adsorption and a significant increase in the seeding efficiency of BMSCs (p = 0.027). In the calvarial defects implanted with BMSC-seeded poly(LLA-co-CL)/nDPs scaffolds, live imaging at 12 weeks discloses a significant increase in osteogenic metabolic activity (p = 0.016). Microcomputed tomography, confirmed by histological data, reveals a substantial increase in bone volume (p = 0.021). The results show that compared with conventional poly(LLA-co-CL) scaffolds those functionalized with nDPs promote osteogenic metabolic activity and mineralization capacity. It is concluded that poly(LLA-co-CL) composite matrices functionalized with nDPs enhance osteoconductivity and therefore warrant further study as potential scaffolding material for bone tissue engineering. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

THERMALLY STABLE PERFLUORINATED POLYMERS

DTIC Science & Technology

structure to cyclic product from perfluoroglutaronitrile and N2H4, opening of this cyclic product with polymerization to poly(N2-imidoyl perfluoroglutar ...Work on the 1,2,4-triazole polymer system, in which these heterocyclic groups are connected by perfluoroalkylene chains, included assignment of...hydrazidine), and synthesis of poly( perfluoropropylene - 1,2,4- triazole) both from the poly(imidoyl hydrazidine) and directly from the original cyclic

CRACC-CRACC Interaction between Kupffer and NK Cells Contributes to Poly I:C/D-GalN Induced Hepatitis

PubMed Central

Li, Yangxi; Cao, Guoshuai; Zheng, Xiaodong; Wang, Jun; Wei, Haiming; Tian, Zhigang; Sun, Rui

2013-01-01

CD2-like receptor activating cytotoxic cells (CRACC) is known as a critical activating receptor of natural killer (NK) cells. We have previously reported that NK cells contribute to Poly I:C/D-galactosamine (D-GalN)-induced fulminant hepatitis. Since natural killer group 2, member D (NKG2D) is considered critical but not the only activating receptor for NK cells, we investigated the role of CRACC in this model. We found that CRACC was abundant on hepatic NK cells but with low expression levels on Kupffer cells under normal conditions. Expression of CRACC on NK cells and Kupffer cells was remarkably upregulated after poly I:C injection. Hepatic CRACC mRNA levels were also upregulated in Poly I:C/D-GalN-treated mice, and correlated positively with the serum alanine aminotransferase (ALT) levels. CRACC expression on Kupffer cells was specifically silenced by nano-particle encapsulated siRNA in vivo, which significantly reduced Poly I:C/D-GalN-induced liver injury. In co-culture experiments, it was further verified that silencing CRACC expression or blockade of CRACC activation by mAb reduced the production of interferon (IFN)-γ and tumor necrosis factor (TNF)-α. Collectively, our findings suggest that CRACC-CRACC interaction between NK cells and resident Kupffer cells contributes to Poly I:C/D-GalN-induced fulminant hepatitis. PMID:24098802

Modification of HTPB-based polyurethane with temperature-sensitive poly(N-isopropyl acrylamide) for biomaterial usage.

PubMed

Yang, Jen Ming; Yang, Shu Jyuan; Lin, Hao Tzu; Chen, Jan Kan

2007-01-01

Hydroxyl-terminated polybutadiene (HTPB)-based polyurethane with dimethyol propionic acid (DPA) as chain extender was synthesized by solution polymerization. The HTPB-based polyurethane was modified by UV radiation with N-isopropyl acrylamide monomer to get poly(N-isopropyl acrylamide)-modified polyurethane (PUDPANIPAAm). The cohesive energy (E(coh)), molar volume (V), solubility parameter (delta), molecular weight (W(M)), volume per gram (V(g)), and the density (1/V(g)) of PUDPANIPAAm were calculated by group contribution methods. To evaluate the application of PUDPANIPAAm for wound dressing and transplantation of cell sheet, the measurement of water content, water vapor transmission rate, and gas permeation on the PUDPANIPAAm membrane was evaluated. The biocompatibility of these membranes, cell adhesion, and proliferation assay were conducted in the cell culture. The effect of thermosensitivity of poly(N-isopropyl acrylamide) on cell detachment was also evaluated in the primary study. The results showed that these PUDPANIPAAm membranes are thermosensitive. The modification of PU with poly(N-isopropyl acrylamide) reduced the water vapor transmission rate and permeability of gas through PUDPANIPAAm membrane. PUDPANIPAAm membranes could support cell adhesion and growth. Owing to the thermosensitive nature of poly(N-isopropyl acrylamide), the relative cell numbers detached from PUDPANIPAAm membranes were larger than those detached from the polystyrene dish. 2006 Wiley Periodicals, Inc.

Safety and complications of absorbable threads made of poly-L-lactic acid and poly lactide/glycolide: Experience with 148 consecutive patients.

PubMed

Sarigul Guduk, Sukran; Karaca, Nezih

2018-04-01

Thread lifting is a minimally invasive procedure for lifting and repositioning tissues. Few articles with absorbable sutures exist in the literature. Furthermore there is no study focusing on complications of absorbable sutures. To describe complications of thread lifting using a totally absorbable suture composed of poly-L-lactic acid affixed with poly lactide/glycolide cones. Data regarding complications were analyzed retrospectively for 148 patients underwent thread lifting between June 2014 and February 2017. A total of 321 pairs of sutures used in the 148 patients studied. Overall 40 (27%) patients had complications regarded as minimal or moderate without permanent sequela. The most common complication was skin dimpling and irregularity (n = 17, 11.4%) followed by ecchymosis (n = 12, 8.1%), suture extrusion (n = 4, 2.7%), and pain (n = 4, 2.7%) Except one patient, dimpling, and irregularity resolved in all patients after 3-7 days spontaneously. Suture migration was observed in 2 (1.35%) patients. Hematoma and infection were seen in 2 patients one for each. The procedure using sutures made of absorbable poly-L-lactic acid and poly lactide/glycolide is a relatively safe procedure without major complications. © 2018 Wiley Periodicals, Inc.

Surface Grafting of Thermoresponsive Microgel Nanoparticles (Postprint)

DTIC Science & Technology

2011-01-01

and cell immobilization, as biosensors, and for in vivo drug delivery .33,34,36,49–53 PNIPAM-containing microgels have been synthesized and...2007, 25, 577–583. 51 J. Jagur-Grodzinski, Polym. Adv. Technol., 2010, 21, 27–47.Soft Matter52 M. Hamidi, A. Azadi and P. Rafiei,Adv. Drug Delivery ...prospective applications in micro- and nanofluidics, biocompatible materials, controlled drug release, nano- and biotribology, controlled cell growth

Thermophysical Properties of Aircraft Structural Materials in Solid and Molten States. A Comprehensive Survey of Available Data and Feasibility Study of Estimation and Measurement.

DTIC Science & Technology

1974-08-01

methylmethacrylate and 0-100% methacrylic acid . 25-300 90025 Polymethacrylic acid . 50-200 66583 Polyethylm ethacrylate, poly-n-butyl acrylate, and...Polyacrylic acid and some of its salts (H, Na, Cu, Hg). 10. Lucite "Lucite" is a trade name of DuPont for polymethylmethacrylate (PMMA). The other trade name...2.2 40338 7.13 mm before and after methacrylate) fading. Poly(n-butyl 300 2.0-15.0 19814 methacrylate) Poly(acrylic acid ) 300 3-7 34840 Poly( ethylene

Cadmium-free quantum dot light emitting devices: energy-transfer realizing pure blue emission.

PubMed

Ji, Wenyu; Jing, Pengtao; Fan, Yi; Zhao, Jialong; Wang, Yunjun; Kong, Xianggui

2013-01-01

In this study, deep blue, pure electroluminescence (EL) at 441.5 nm from a ZnSe/ZnS quantum dot light-emitting device (QD-LED) is obtained by using poly (4-butylphenyl-diphenyl-amine) (poly-TPD) as the hole-transport layer (HTL) to open up the channel for energy transfer from poly-TPD to QDs. The emission originating from HTL is observed in the QD-LED with N,N'-bis (tolyl)-N,N'-diphenyl-1,1'-biphenyl-4,4'-diamine functionalized with two styryl groups (2-TPD) as the HTL due to inefficient energy-transfer from 2-TPD to QDs. The poly-TPD based device exhibits color-saturated blue emission with a narrow spectral bandwidth of full width at half maximum (~17.2 nm). These results explore the operating mechanism of the QD EL and signify a remarkable progress in deep blue QD-LEDs based on environmental-friendly QD materials.

Reversible addition-fragmentation chain transfer polymerization of N-isopropylacrylamide: a comparison between a conventional and a fast initiator.

PubMed

Bouchékif, Hassen; Narain, Ravin

2007-09-27

The reversible addition-fragmentation chain transfer (RAFT) polymerization of N-isopropylacrylamide (NIPAM) was studied to determine the reasons for deviation of experimental molecular weights to lower molecular weight at high monomer conversion when S-1-dodecyl-S-(alpha,alpha'-dimethyl-alpha' '-acetic acid)trithiocarbonate (CTAm) and S,S-bis(alpha,alpha'-dimethyl-alpha' '-acetic acid)trithiocarbonate (CTAd) were used as RAFT agents at 65 degrees C. For this purpose, experiments were performed in N,N'-dimethylformamide (DMF) at the NIPAM/CTA ratio of 200 with initiators capable of yielding fast and slow initiation, respectively by photochemical and thermal process, either at ambient temperature or at 65 degrees C. When the polymerization of NIPAM was conducted under these conditions with Irgacure-2959 (IRGC) as photoinitiator, a continuing supply of primary radicals by incremental initiator addition was required to achieve reasonably high conversion. This effect was also apparent by the loss of linearity of the first-order kinetic plot with a conventional initiator (4,4-azobis(4-cyanovaleric acid) (ACVA) as azo-initiator, 10h (t1/2) decomposition at 65 degrees C) indicating that steady-state concentration of the macroradical decreases significantly with the initiator consumption. Nevertheless, polymers with predictable number-average molecular weight Mn (i.e., based on [monomer]/([CTA] + [initiator]) ratio) and narrow polydispersities were obtained (PDIs < 1.2) with CTAm indicating that the process of chain growth was controlled. When CTAd was used, instead of CTAm, the polymers obtained were characterized by a larger polydispersity (1.2 < PDIs < 1.3). The so-called "living steady-state concentration" in chain equilibration together with the linear dependence of Mn vs conversion was observed only when the 200/1 NIPAM/CTA mixture in DMF was subjected to a permanent photoirradiation at 65 degrees C. With ACVA, the deviation of the experimentally measured molecular weights at high conversion was accounted for by the simultaneous self-initiated polymerization of NIPAM with the controlled process in the presence of CTA at 65 degrees C. Similar drift from the linear dependence Mn vs conversion was also observed at 65 degrees C when a significant number of low molecular weight polymer chains were generated intentionally by photodecomposition of IRGC.

Synthesis and characterization of poly(L-alanine)-block-poly(ethylene glycol) monomethyl ether as amphiphilic biodegradable co-polymers.

PubMed

Zhang, Guolin; Ma, Jianbiao; Li, Yanhong; Wang, Yinong

2003-01-01

Di-block co-polymers of poly(L-alanine) with poly(ethylene glycol) monomethyl ether (MPEG) were synthesized as amphiphilic biodegradable co-polymers. The ring-opening polymerization of N-carboxy-L-alanine anhydride (NCA) in dichloromethane was initiated by amino-terminated poly(ethylene glycol) monomethyl ether (MPEG-NH2, M(n) = 2000) to afford poly(L-alanine)-block-MPEG. The weight ratio of two blocks in the co-polymers could be altered by adjusting the feeding ratio of NCA to MPEG-NH2. Their chemical structures were characterized on the basis of infrared spectrometry and nuclear magnetic resonance. According to circular dichroism measurement, the poly(L-alanine) chain on the co-polymers in an aqueous medium had a alpha-helix conformation. Two melting points from MPEG block and poly(L-alanine), respectively, could be observed in differential scanning calorimetry curves of the co-polymers, suggesting that a micro-domain phase separation appeared in their bulky states. The co-polymers could take up some water and the capacity was dependent on the ratio of poly(L-alanine) block to MPEG. Such co-polymers might be useful in drug-delivery systems and other biomedical applications.

Synthesis and Characterization of Multiwalled Carbon Nanotubes/Poly(HEMA-co-MMA) by Utilizing Click Chemistry.

PubMed

Bach, Long Giang; Cao, Xuan Thang; Islam, Md Rafiqul; Jeong, Yeon Tae; Kim, Jong Su; Lim, Kwon Taek

2016-03-01

The hybrid material consisting of multi walled carbon nanotubes (MWNTs) and poly(2-hydroxyethylmethacrylate-co-methylmethacrylate) [poly(HEMA-co-MMA)] was synthesized by a combination of RAFT and Click chemistry. In the primary stage, the copolymer poly(HEMA-co-MMA) was prepared by applying RAFT technique. Alkynyl side groups were incorporated onto the poly(HEMA-co-MMA) backbone by esterification reaction. Then, MWNTs-N3 was prepared by treating MWNTs with 4-azidobutylamine. The click coupling reaction between azide-functionalized MWNTs (MWNTs-N3) and the alkyne-functionalized random copolymer ((HEMA-co-MMA)-Alkyne) with the Cu(I)-catalyzed [3+2] Huisgen cycloaddition afforded the hybrid compound. The structure and properties of poly(MMA-co-HEMA)-g-MWNTs were investigated by FT-IR, EDX and TGA measurements. The copolymer brushes were observed to be immobilized onto the functionalized MWNTs by SEM and TEM analysis.

Development of injectable hydrogels for nucleus pulposus replacement

NASA Astrophysics Data System (ADS)

Thomas, Jonathan D.

Intervertebral disc degeneration has been reported as the underlying cause for 75% of cases of lower back pain and is marked by dehydration of the nucleus pulposus within the intervertebral disc. There have been many implant designs to replace the nucleus pulposus. Some researchers have proposed the replacement of the nucleus pulposus with hydrogel materials. The insertion of devices made from these materials further compromises the annulus of the disc. An ideal nucleus replacement could be injected into the disc space and form a solid in vivo. However, injectable replacements using curing elastomers and thermoplastic materials are not ideal because of the potentially harmful exothermic heat evolved from their reactions and the toxicity of the reactants used. We propose a hydrogel system that can be injected as a liquid at 25°C and solidified to yield a hydrogel within the intervertebral disc at 37°C. In aqueous solutions, these polymers have Lower Critical Solution Temperatures (LCST) between 25-37°C, making them unique candidate materials for this application. Poly(N-isopropylacrylamide) (PNIPAAm) is the most widely studied LCST polymer due to its drastic transition near body temperature. However, by itself, pure PNIPAAm forms a hydrogel that has low water content and can readily undergo plastic deformation. To increase the water content and impart elasticity to PNIPAAm hydrogels, grafted and branched hydrogel systems were created that incorporated the thermogelling PNIPAAm and hydrophilic poly(ethylene glycol) (PEG). In this research, the effects of polymer composition and monomer to initiator ratio, which controls polymer MW, on the in vitro swelling properties (mass, chemical, and compressive mechanical stability) of hydrogels formed from aqueous solutions of these polymers were evaluated. Immersion studies were also conducted in solutions to simulate the osmotic environment of the nucleus pulposus. The effects of repeated compression and unloading cycles on the water content and dimensional recovery of hydrogels made from three candidate polymer formulations were also determined. Unlike PNIPAAm and PEG grafted PNIPAAm hydrogels, PEG branched hydrogels have covalently linked networks. Addition of 7 mol% PEG branches to PNIPAAm resulted in a hydrogel with a higher water content and better elastic recovery than hydrogels made from pure PNIPAAm. PEG branched PNIPAAm hydrogels were shown to have mass, chemical, and compressive mechanical stability in vitro. Furthermore, these hydrogels showed superior dimensional recovery after compressive cycling than pure PNIPAAm and PEG grafted PNIPAAm hydrogels. The 7 mol% PEG branched PNIPAAm hydrogels have suitable swelling and mechanical properties to potentially serve as a nucleus pulposus replacement.

Charge-Carrier Balance for Highly Efficient Inverted Planar Heterojunction Perovskite Solar Cells.

PubMed

Chen, Ke; Hu, Qin; Liu, Tanghao; Zhao, Lichen; Luo, Deying; Wu, Jiang; Zhang, Yifei; Zhang, Wei; Liu, Feng; Russell, Thomas P; Zhu, Rui; Gong, Qihuang

2016-12-01

The charge-carrier balance strategy by interface engineering is employed to optimize the charge-carrier transport in inverted planar heterojunction perovskite solar cells. N,N-Dimethylformamide-treated poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) and poly(methyl methacrylate)-modified PCBM are utilized as the hole and electron selective contacts, respectively, leading to a high power conversion efficiency of 18.72%. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tissue engineering: construction of a multicellular 3D scaffold for the delivery of layered cell sheets.

PubMed

Turner, William S; Sandhu, Nabjot; McCloskey, Kara E

2014-10-03

Many tissues, such as the adult human hearts, are unable to adequately regenerate after damage.(2,3) Strategies in tissue engineering propose innovations to assist the body in recovery and repair. For example, TE approaches may be able to attenuate heart remodeling after myocardial infarction (MI) and possibly increase total heart function to a near normal pre-MI level.(4) As with any functional tissue, successful regeneration of cardiac tissue involves the proper delivery of multiple cell types with environmental cues favoring integration and survival of the implanted cell/tissue graft. Engineered tissues should address multiple parameters including: soluble signals, cell-to-cell interactions, and matrix materials evaluated as delivery vehicles, their effects on cell survival, material strength, and facilitation of cell-to-tissue organization. Studies employing the direct injection of graft cells only ignore these essential elements.(2,5,6) A tissue design combining these ingredients has yet to be developed. Here, we present an example of integrated designs using layering of patterned cell sheets with two distinct types of biological-derived materials containing the target organ cell type and endothelial cells for enhancing new vessels formation in the "tissue". Although these studies focus on the generation of heart-like tissue, this tissue design can be applied to many organs other than heart with minimal design and material changes, and is meant to be an off-the-shelf product for regenerative therapies. The protocol contains five detailed steps. A temperature sensitive Poly(N-isopropylacrylamide) (pNIPAAM) is used to coat tissue culture dishes. Then, tissue specific cells are cultured on the surface of the coated plates/micropattern surfaces to form cell sheets with strong lateral adhesions. Thirdly, a base matrix is created for the tissue by combining porous matrix with neovascular permissive hydrogels and endothelial cells. Finally, the cell sheets are lifted from the pNIPAAM coated dishes and transferred to the base element, making the complete construct.

Metal ion promoted hydrogels for bovine serum albumin adsorption: Cu(II) and Co(II) chelated poly[(N-vinylimidazole)-maleic acid].

PubMed

Pekel, Nursel; Salih, Bekir; Güven, Olgun

2005-05-10

Poly[(N-vinylimidazole)-maleic acid] (poly(VIm-MA)), copolymeric hydrogels were prepared by gamma-irradiating ternary mixtures of N-vinylimidazole-maleic acid-water in a (60)Co-gamma source. Cu(II) and Co(II) ions were chelated within the gels at pH=5.0. The maximum adsorption capacity of the gels were 3.71 mmol/g dry gel for Cu(II) and 1.25 mmol/g dry gel for Co(II) at pH=5.0. The swelling ratios of the gels were 1200% for poly(VIm-MA), 60 and 45% for Cu(II) and Co(II)-chelated poly(VIm-MA) gels at pH=5.0 in acetate buffer solution. These affinity gels with different swelling ratios for plain poly(VIm-MA), Cu(II)-, and Co(II)-chelated poly(VIm-MA), in acetate and phosphate buffers were used in the bovine serum albumin (BSA) adsorption/desorption studies in batch reactor. The maximum BSA adsorption capacities of the gels were 0.38 g/g dry gel for plain, 0.88 g/g dry gel for Cu(II)-chelated poly(VIm-MA) and 1.05 g/g dry gel for Co(II)-chelated poly(VIm-MA) gels. Adsorption capacity of BSA by the gels was reduced dramatically by increasing the ionic strength adjusted with NaCl. More than 95% of BSA were desorbed in 10 h in desorption medium containing 0.1M of EDTA for metal ion-chelated gels at pH=4.7.

Modular Small Diameter Vascular Grafts with Bioactive Functionalities

PubMed Central

Neufurth, Meik; Wang, Xiaohong; Tolba, Emad; Dorweiler, Bernhard; Schröder, Heinz C.; Link, Thorben; Diehl-Seifert, Bärbel; Müller, Werner E. G.

2015-01-01

We report the fabrication of a novel type of artificial small diameter blood vessels, termed biomimetic tissue-engineered blood vessels (bTEBV), with a modular composition. They are composed of a hydrogel scaffold consisting of two negatively charged natural polymers, alginate and a modified chitosan, N,O-carboxymethyl chitosan (N,O-CMC). Into this biologically inert scaffold two biofunctionally active biopolymers are embedded, inorganic polyphosphate (polyP) and silica, as well as gelatin which exposes the cell recognition signal, Arg-Gly-Asp (RGD). These materials can be hardened by exposure to Ca2+ through formation of Ca2+ bridges between the polyanions, alginate, N,O-CMC, and polyP (alginate-Ca2+-N,O-CMC-polyP). The bTEBV are formed by pressing the hydrogel through an extruder into a hardening solution, containing Ca2+. In this universal scaffold of the bTEBV biomaterial, polycations such as poly(l-Lys), poly(d-Lys) or a His/Gly-tagged RGD peptide (three RGD units) were incorporated, which promote the adhesion of endothelial cells to the vessel surface. The mechanical properties of the biopolymer material (alginate-Ca2+-N,O-CMC-polyP-silica) revealed a hardness (elastic modulus) of 475 kPa even after a short incubation period in CaCl2 solution. The material of the artificial vascular grafts (bTEBVs with an outer size 6 mm and 1.8 mm, and an inner diameter 4 mm and 0.8 mm, respectively) turned out to be durable in 4-week pulsatile flow experiments at an alternating pressure between 25 and 100 mbar (18.7 and 75.0 mm Hg). The burst pressure of the larger (smaller) vessels was 850 mbar (145 mbar). Incorporation of polycationic poly(l-Lys), poly(d-Lys), and especially the His/Gly-tagged RGD peptide, markedly increased the adhesion of human, umbilical vein/vascular endothelial cells, EA.HY926 cells, to the surface of the hydrogel. No significant effect of the polyP samples on the clotting of human plasma is measured. We propose that the metabolically degradable polymeric scaffold bTEBV is a promising biomaterial for future prosthetic vascular grafts. PMID:26204529

Evaluation of Electrical Characteristics and Trap-State Density in Bottom-Gate Polycrystalline Thin Film Transistors Processed with High-Pressure Water Vapor Annealing

NASA Astrophysics Data System (ADS)

Kunii, Masafumi

2006-02-01

This paper discusses electrical characteristics and trap-state density in polycrystalline silicon (poly-Si) used in bottom-gate poly-Si thin film transistors (TFTs) processed with high-pressure water vapor annealing (HWA). The threshold voltage uniformity of the HWA-processed TFTs is improved by 42% for N-channel and 38% for P-channel TFTs in terms of standard deviation, and carrier mobility is enhanced by 10% or greater for both N- and P-channel TFTs than those TFTs processed conventionally. Subthreshold swing is also improved by HWA, showing that HWA postannealing is effective for improving the Si/SiO2 interface of the bottom-gate TFTs. Two types of TFTs having different poly-Si crystallinities are examined to investigate carrier transport in poly-Si processed by HWA postannealing. The evaluation of trap-state density for the two types of poly-Si reveals that HWA postannealing is more efficient for N-channel than for P-channel TFTs. Furthermore, HWA postannealing is more effective for poly-Si with high crystallinity to improve TFT characteristics. The analysis of the trap-state distributions and the activation energy of TFT drain current indicate that HWA deactivates dangling bonds highly localized at poly-Si grain boundaries (GBs). Thus, HWA postannealing effects can be interpreted by a GB barrier potential model similar to that applied to conventional hydrogenation.

Assessing the transport potential of polymeric nanocapsules developed for crop protection.

PubMed

Petosa, Adamo Riccardo; Rajput, Faraz; Selvam, Olivia; Öhl, Carolin; Tufenkji, Nathalie

2017-03-15

Nanotechnology is increasingly important in the agricultural sector, with novel products being developed to heighten crop yields and increase pesticide efficacy. Herein, the transport potential of different polymeric nanocapsules (nCAPs) developed as pesticide delivery vehicles was assessed in model soil systems. The nCAPs examined are (i) poly(acrylic acid)-based (nCAP1), (ii) poly(methacrylic acid)-ran-poly(ethyl acrylate) copolymer-based (nCAP2), (iii) poly(methacrylic acid-ran-styrene) copolymer-based (nCAP3), and (iv) poly(methacrylic acid-ran-butylmethacrylate)-based (nCAP4). nCAP mobility was examined in columns packed with agricultural loamy sand saturated with artificial porewater containing Ca 2+ and Mg 2+ cations (10 mM ionic strength, pH 6 and 8). Furthermore, the impact of (i) cation species, (ii) sand type, and (iii) ammonium polyphosphate fertilizer on the transport potential of a nanoformulation combining nCAP4 capsules and the pyrethroid bifenthrin (nCAP4-BIF) was examined and compared to a commercial bifenthrin formulation (Capture ® LFR). Although nCAP4-BIF and Capture ® LFR formulations were highly mobile in quartz sand saturated with 10 mM NaNO 3 (≥95% elution), they were virtually immobile in the presence of 10% ammonium polyphosphate fertilizer. The presence of Ca 2+ and Mg 2+ did not hinder nCAP4-BIF elution in quartz sand saturated with 10 mM standard CIPAC D synthetic porewater; however, limited Capture ® LFR transport (<10% elution) was observed under the same conditions. Capture ® LFR also exhibited limited mobility in the presence or absence of fertilizer in loamy sand saturated with divalent salt solutions, whereas nCAP4-BIF exhibited increased elution with time and enhanced transport upon the addition of fertilizer. Overall, nCAP4 is a promising delivery vehicle in pyrethroid nanoformulations such as nCAP4-BIF. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fabrication of n-type Si nanostructures by direct nanoimprinting with liquid-Si ink

NASA Astrophysics Data System (ADS)

Takagishi, Hideyuki; Masuda, Takashi; Yamazaki, Ken; Shimoda, Tatsuya

2018-01-01

Nanostructures of n-type amorphous silicon (a-Si) and polycrystalline silicon (poly-Si) with a height of 270 nm and line widths of 110-165 nm were fabricated directly onto a substrate through a simple imprinting process that does not require vacuum conditions or photolithography. The n-type Liquid-Si ink was synthesized via photopolymerization of cyclopentasilane (Si5H10) and white phosphorus (P4). By raising the temperature from 160 °C to 200 °C during the nanoimprinting process, well-defined angular patterns were fabricated without any cracking, peeling, or deflections. After the nanoimprinting process, a-Si was produced by heating the nanostructures at 400°C-700 °C, and poly-Si was produced by heating at 800 °C. The dopant P diffuses uniformly in the Si films, and its concentration can be controlled by varying the concentration of P4 in the ink. The specific resistance of the n-type poly-Si pattern was 7.0 × 10-3Ω ṡ cm, which is comparable to the specific resistance of flat n-type poly-Si films.

Efficiency of solution-processed multilayer polymer light-emitting diodes using charge blocking layers

NASA Astrophysics Data System (ADS)

Kasparek, Christian; Rörich, Irina; Blom, Paul W. M.; Wetzelaer, Gert-Jan A. H.

2018-01-01

By blending semiconducting polymers with the cross-linkable matrix ethoxylated-(4)-bisphenol-a-dimethacrylate (SR540), an insoluble layer is acquired after UV-illumination. Following this approach, a trilayer polymer light-emitting diode (PLED) consisting of a blend of poly[N,N'-bis(4-butylphenyl)-N,N'-bis(phenyl)-benzidine] (poly-TPD) and SR540 as an electron-blocking layer, Super Yellow-Poly(p-phenylene vinylene) (SY-PPV) blended with SR540 as an emissive layer, and poly(9,9-di-n-octylfluorenyl-2,7-diyl) as a hole-blocking layer is fabricated from solution. The trilayer PLED shows a 23% increase in efficiency at low voltage as compared to a single layer SY-PPV PLED. However, at higher voltage, the advantage in current efficiency gradually decreases. A combined experimental and modelling study shows that the increased efficiency is not only due to the elimination of exciton quenching at the electrodes but also due to suppressed nonradiative trap-assisted recombination due to carrier confinement. At high voltages, holes can overcome the hole-blocking barrier, which explains the efficiency roll-off.

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

Design and application of ion-implanted polySi passivating contacts for interdigitated back contact c-Si solar cells

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

Yang, Guangtao; Ingenito, Andrea; Hameren, Nienke van

2016-01-18

Ion-implanted passivating contacts based on poly-crystalline silicon (polySi) are enabled by tunneling oxide, optimized, and used to fabricate interdigitated back contact (IBC) solar cells. Both n-type (phosphorous doped) and p-type (boron doped) passivating contacts are fabricated by ion-implantation of intrinsic polySi layers deposited via low-pressure chemical vapor deposition and subsequently annealed. The impact of doping profile on the passivation quality of the polySi doped contacts is studied for both polarities. It was found that an excellent surface passivation could be obtained by confining as much as possible the implanted-and-activated dopants within the polySi layers. The doping profile in the polySimore » was controlled by modifying the polySi thickness, the energy and dose of ion-implantation, and the temperature and time of annealing. An implied open-circuit voltage of 721 mV for n-type and 692 mV for p-type passivating contacts was achieved. Besides the high passivating quality, the developed passivating contacts exhibit reasonable high conductivity (R{sub sh n-type} = 95 Ω/□ and R{sub sh p-type} = 120 Ω/□). An efficiency of 19.2% (V{sub oc} = 673 mV, J{sub sc} = 38.0 mA/cm{sup 2}, FF = 75.2%, and pseudo-FF = 83.2%) was achieved on a front-textured IBC solar cell with polySi passivating contacts as both back surface field and emitter. By improving the front-side passivation, a V{sub OC} of 696 mV was also measured.« less

Improved Social Interaction, Recognition and Working Memory with Cannabidiol Treatment in a Prenatal Infection (poly I:C) Rat Model

PubMed Central

Osborne, Ashleigh L; Solowij, Nadia; Babic, Ilijana; Huang, Xu-Feng; Weston-Green, Katrina

2017-01-01

Neuropsychiatric disorders such as schizophrenia are associated with cognitive impairment, including learning, memory and attention deficits. Antipsychotic drugs are limited in their efficacy to improve cognition; therefore, new therapeutic agents are required. Cannabidiol (CBD), the non-intoxicating component of cannabis, has anti-inflammatory, neuroprotective and antipsychotic-like properties; however, its ability to improve the cognitive deficits of schizophrenia remains unclear. Using a prenatal infection model, we examined the effect of chronic CBD treatment on cognition and social interaction. Time-mated pregnant Sprague-Dawley rats (n=16) were administered polyinosinic-polycytidilic acid (poly I:C) (POLY; 4 mg/kg) or saline (CONT) at gestation day 15. Male offspring (PN56) were injected twice daily with 10 mg/kg CBD (CONT+CBD, POLY+CBD; n=12 per group) or vehicle (VEH; CONT+VEH, POLY+VEH; n=12 per group) for 3 weeks. Body weight, food and water intake was measured weekly. The Novel Object Recognition and rewarded T-maze alternation tests assessed recognition and working memory, respectively, and the social interaction test assessed sociability. POLY+VEH offspring exhibited impaired recognition and working memory, and reduced social interaction compared to CONT+VEH offspring (p<0.01). CBD treatment significantly improved recognition, working memory and social interaction deficits in the poly I:C model (p<0.01 vs POLY+VEH), did not affect total body weight gain, food or water intake, and had no effect in control animals (all p>0.05). In conclusion, chronic CBD administration can attenuate the social interaction and cognitive deficits induced by prenatal poly I:C infection. These novel findings present interesting implications for potential use of CBD in treating the cognitive deficits and social withdrawal of schizophrenia. PMID:28230072

Improved Social Interaction, Recognition and Working Memory with Cannabidiol Treatment in a Prenatal Infection (poly I:C) Rat Model.

PubMed

Osborne, Ashleigh L; Solowij, Nadia; Babic, Ilijana; Huang, Xu-Feng; Weston-Green, Katrina

2017-06-01

Neuropsychiatric disorders such as schizophrenia are associated with cognitive impairment, including learning, memory and attention deficits. Antipsychotic drugs are limited in their efficacy to improve cognition; therefore, new therapeutic agents are required. Cannabidiol (CBD), the non-intoxicating component of cannabis, has anti-inflammatory, neuroprotective and antipsychotic-like properties; however, its ability to improve the cognitive deficits of schizophrenia remains unclear. Using a prenatal infection model, we examined the effect of chronic CBD treatment on cognition and social interaction. Time-mated pregnant Sprague-Dawley rats (n=16) were administered polyinosinic-polycytidilic acid (poly I:C) (POLY; 4 mg/kg) or saline (CONT) at gestation day 15. Male offspring (PN56) were injected twice daily with 10 mg/kg CBD (CONT+CBD, POLY+CBD; n=12 per group) or vehicle (VEH; CONT+VEH, POLY+VEH; n=12 per group) for 3 weeks. Body weight, food and water intake was measured weekly. The Novel Object Recognition and rewarded T-maze alternation tests assessed recognition and working memory, respectively, and the social interaction test assessed sociability. POLY+VEH offspring exhibited impaired recognition and working memory, and reduced social interaction compared to CONT+VEH offspring (p<0.01). CBD treatment significantly improved recognition, working memory and social interaction deficits in the poly I:C model (p<0.01 vs POLY+VEH), did not affect total body weight gain, food or water intake, and had no effect in control animals (all p>0.05). In conclusion, chronic CBD administration can attenuate the social interaction and cognitive deficits induced by prenatal poly I:C infection. These novel findings present interesting implications for potential use of CBD in treating the cognitive deficits and social withdrawal of schizophrenia.

Poly[n]catenanes: Synthesis of molecular interlocked chains

NASA Astrophysics Data System (ADS)

Wu, Qiong; Rauscher, Phillip M.; Lang, Xiaolong; Wojtecki, Rudy J.; de Pablo, Juan J.; Hore, Michael J. A.; Rowan, Stuart J.

2017-12-01

As the macromolecular version of mechanically interlocked molecules, mechanically interlocked polymers are promising candidates for the creation of sophisticated molecular machines and smart soft materials. Poly[n]catenanes, where the molecular chains consist solely of interlocked macrocycles, contain one of the highest concentrations of topological bonds. We report, herein, a synthetic approach toward this distinctive polymer architecture in high yield (~75%) via efficient ring closing of rationally designed metallosupramolecular polymers. Light-scattering, mass spectrometric, and nuclear magnetic resonance characterization of fractionated samples support assignment of the high-molar mass product (number-average molar mass ~21.4 kilograms per mole) to a mixture of linear poly[7-26]catenanes, branched poly[13-130]catenanes, and cyclic poly[4-7]catenanes. Increased hydrodynamic radius (in solution) and glass transition temperature (in bulk materials) were observed upon metallation with Zn2+.

Poly(ethylene oxide) surfactant polymers.

PubMed

Vacheethasanee, Katanchalee; Wang, Shuwu; Qiu, Yongxing; Marchant, Roger E

2004-01-01

We report on a series of structurally well-defined surfactant polymers that undergo surface-induced self-assembly on hydrophobic biomaterial surfaces. The surfactant polymers consist of a poly(vinyl amine) backbone with poly(ethylene oxide) and hexanal pendant groups. The poly(vinyl amine) (PVAm) was synthesized by hydrolysis of poly(N-vinyl formamide) following free radical polymerization of N-vinyl formamide. Hexanal and aldehyde-terminated poly(ethylene oxide) (PEO) were simultaneously attached to PVAm via reductive amination. Surfactant polymers with different PEO:hexanal ratios and hydrophilic/hydrophobic balances were prepared, and characterized by FT-IR, 1H-NMR and XPS spectroscopies. Surface active properties at the air/water interface were determined by surface tension measurements. Surface activity at a solid surface/water interface was demonstrated by atomic force microscopy, showing epitaxially molecular alignment for surfactant polymers adsorbed on highly oriented pyrolytic graphite. The surfactant polymers described in this report can be adapted for simple non-covalent surface modification of biomaterials and hydrophobic surfaces to provide highly hydrated interfaces.

Nanocomposites based on self-assembly poly(hydroxypropyl methacrylate)-block-poly(N-phenylmaleimide) and Fe3O4-NPs. Thermal stability, morphological characterization and optical properties

NASA Astrophysics Data System (ADS)

Pizarro, Guadalupe del C.; Marambio, Oscar G.; Jeria-Orell, Manuel; Sánchez, Julio; Oyarzún, Diego P.

2018-02-01

The current work presents the synthesis, characterization and preparation of organic-inorganic hybrid polymer films that contain inorganic magnetic nanoparticles (NPs). The block copolymer, prepared by Atom-Transfer Radical Polymerization (ATRP), was used as a nanoreactor for iron oxide NPs. The NPs were embedded in poly(hydroxypropyl methacrylate)-block-poly(N-phenylmaleimide) matrix. The following topographical modifications of the surface of the film were specially analyzed: control of pore features and changes in surface roughness. Finally, the NPs functionality inside the polymer matrix and how it may affect the thermal and optical properties of the films were assessed.

PH-Sensitive WO(3)-Based Microelectrochemical Transistors.

DTIC Science & Technology

1986-09-22

electronics, microelectrochemistry, microelectrodes, surface L- modification, molecuale based transistors, polyaniline , poly-3-methylthiophene Chemical...polymer, as in the cases of polypyrrole,8 poly(N-methyl pyrrole), 8b polyaniline , 9 or poly(3-methylthiophene),1 0 the polymer- % .4_. connected...Polypyrrole, 8 polyaniline , 9 and poly(3-methylthiophene) I0 are similar in that they are conducting when oxidized, and transistors based on these materials

Self-Decontaminating Fibrous Materials Reactive toward Chemical Threats.

PubMed

Bromberg, Lev; Su, Xiao; Martis, Vladimir; Zhang, Yunfei; Hatton, T Alan

2016-07-13

Polymers that possess highly nucleophilic pyrrolidinopyridine (Pyr) and primary amino (vinylamine, VAm) groups were prepared by free-radical copolymerization of N,N-diallylpyridin-4-amine (DAAP) and N-vinylformamide (NVF) followed by acidic hydrolysis of NVF into VAm. The resulting poly(DAAP-co-VAm-co-NVF) copolymers were water-soluble and reacted with water-dispersible polyurethane possessing a high content of unreacted isocyanate groups. Spray-coating of the nylon-cotton (NYCO), rayon, and poly(p-phenylene terephthalamide) (Kevlar 119) fibers pretreated with phosphoric acid resulted in covalent bonding of the polyurethane with the hydroxyl groups on the fiber surface. A second spray-coating of aqueous solutions of poly(DAAP-co-VAm-co-NVF) on the polyurethane-coated fiber enabled formation of urea linkages between unreacted isocyanate groups of the polyurethane layer and the amino groups of poly(DAAP-co-VAm-co-NVF). Fibers with poly(DAAP-co-VAm-co-NVF) attached were compared with fibers modified by adsorption of water-insoluble poly(butadiene-co-pyrrolidinopyridine) (polyBPP) in terms of the stability against polymer leaching in aqueous washing applications. While the fibers modified by attachment of poly(DAAP-co-VAm-co-NVF) exhibited negligible polymer leaching, over 65% of adsorbed polyBPP detached and leached from the fibers within 7 days. Rayon fibers modified by poly(DAAP-co-VAm-co-NVF) were tested for sorption of dimethyl methylphosphonate (DMMP) in the presence of moisture using dynamic vapor sorption technique. Capability of the fibers modified with poly(DAAP-co-VAm-co-NVF) to facilitate hydrolysis of the sorbed DMMP in the presence of moisture was uncovered. The self-decontaminating property of the modified fibers against chemical threats was tested using a CWA simulant diisopropylfluorophosphate (DFP) in aqueous media at pH 8.7. Fibers modified with poly(DAAP-co-VAm-co-NVF) facilitated hydrolysis of DFP with the half-lives up to an order of magnitude shorter than that of the unmodified fibers. The presented polymers and method of multilayer coating can lead to a development of self-decontaminating textiles and other materials.

Poly(styrene-co-N-methacryloyl-l-phenylalanine methyl ester)-functionalized magnetic nanoparticles as sorbents for the analysis of sodium benzoate in beverages.

PubMed

Ji, Shilei; Li, Nan; Qi, Li; Wang, Minglin

2017-01-01

In this study, poly(styrene-co-N-methacryloyl-l-phenylalanine methyl ester)-functionalized magnetic nanoparticles were constructed and used as magnetic solid-phase extraction sorbents for analysis of food preservatives in beverages. To prepare the poly(amino acid)-based sorbents, N-methacryloyl-l-phenylalanine methyl ester, and styrene served as the functional monomers and modified onto the magnetic nanoparticles via free radical polymerization. Interestingly, compared with propylparaben and potassium sorbate, the proposed poly(amino acid)-based sorbents showed a good selectivity to sodium benzoate. The adsorption capacity of the sorbents to sodium benzoate was 6.08 ± 0.31 mg/g. Moreover, the fast adsorption equilibrium could be reached within 5 min. Further, the resultant poly(amino acid)-based sorbents were applied in the analysis of sodium benzoate in real beverage samples. The results proved that the proposed magnetic solid-phase extraction sorbents have a great potential for the analysis of preservatives in food samples. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biomechanical testing of bioabsorbable cannulated screws for slipped capital femoral epiphysis fixation.

PubMed

Kroeber, Markus W; Rovinsky, David; Haskell, Andrew; Heilmann, Moira; Llotz, Jeff; Otsuka, Norman

2002-06-01

This study compared cannulated 4.5-mm bioabsorbable screws made of self-reinforced poly-levolactic acid to cannulated 4.5-mm steel and titanium screws for resistance to shear stress and ability to generate compression in a polyurethane foam model of slipped capital femoral epiphysis fixation. The maximum shear stress resisted by the three screw types was similar (self-reinforced poly-levolactic acid 371 +/- 146 MPa, steel 442 +/- 43 MPa, and titanium 470 +/- 91 MPa). The maximum compression generated by both the self-reinforced poly-levolactic acid screw (68.5 +/- 3.3 N) and the steel screw (63.3 +/- 5.9 N) was greater than that for the titanium screw (3 +/- 1.4 N, P <.05). These data suggest cannulated self-reinforced poly-levolactic acid screws can be used in the treatment of slipped capital femoral epiphysis because of their sufficient biomechanical strength.

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

Endow, Joshua K.; Rocha, Agostinho Gomes; Baldwin, Amy J.

PolyGly is present in many proteins in various organisms. One example is found in a transmembrane β-barrel protein, translocon at the outer-envelope-membrane of chloroplasts 75 (Toc75). Toc75 requires its N-terminal extension (t75) for proper localization. t75 comprises signals for chloroplast import (n75) and envelope sorting (c75) in tandem. n75 and c75 are removed by stromal processing peptidase and plastidic type I signal peptidase 1, respectively. PolyGly is present within c75 and its deletion or substitution causes mistargeting of Toc75 to the stroma. Here in this study we have examined the properties of polyGly-dependent protein targeting using two soluble passenger proteins,more » the mature portion of the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (mSS) and enhanced green fluorescent protein (EGFP). Both t75-mSS and t75-EGFP were imported into isolated chloroplasts and their n75 removed. Resultant c75-mSS was associated with the envelope at the intermembrane space, whereas c75-EGFP was partially exposed outside the envelope. Deletion of polyGly or substitution of tri-Ala for the critical tri-Gly segment within polyGly caused each passenger to be targeted to the stroma. Transient expression of t75-EGFP in Nicotiana benthamiana resulted in accumulation of c75-EGFP exposed at the surface of the chloroplast, but the majority of the EGFP passenger was found free in the cytosol with most of its c75 attachment removed. Results of circular dichroism analyses suggest that polyGly within c75 may form an extended conformation, which is disrupted by tri-Ala substitution. These data suggest that polyGly is distinct from a canonical stop-transfer sequence and acts as a rejection signal at the chloroplast inner envelope.« less

Enzyme-synthesized Poly(amine-co-esters) as Non-viral Vectors for Gene Delivery

PubMed Central

Liu, Jie; Jiang, Zhaozhong; Zhou, Jiangbing; Zhang, Shengmin; Saltzman, W. Mark

2010-01-01

A family of biodegradable poly(amine-co-esters) was synthesized in one step via enzymatic copolymerization of diesters with amino-substituted diols. Diesters of length C4–C12 (i.e., from succinate to dodecanedioate) were successfully copolymerized with diethanolamines with either an alkyl (methyl, ethyl, n-butyl, t-butyl) or an aryl (phenyl) substituent on the nitrogen. Upon protonation at slightly acidic conditions, these poly(amine-co-esters) readily turned to cationic polyelectrolytes, which were capable of condensing with polyanionic DNA to form nanometer-sized polyplexes. In vitro screening with pLucDNA revealed that two of the copolymers, poly(N-methyldiethyleneamine sebacate) (PMSC) and poly(N-ethyldiethyleneamine sebacate) (PESC), possessed comparable or higher transfection efficiencies compared to Lipofectamine 2000. PMSC/pLucDNA and PESC/pLucDNA nanoparticles had desirable particle sizes (40–70 nm) for cellular uptake and were capable of functioning as proton sponges to facilitate endosomal escape after cellular uptake. These polyplex nanoparticles exhibited extremely low cytotoxicity. Furthermore, in vivo gene transfection experiments revealed that PMSC is a substantially more effective gene carrier than PEI in delivering pLucDNAto cells in tumors in mice. All these properties suggest that poly(amine-co-esters) are promising non-viral vectors for safe and efficient DNA delivery in gene therapy. PMID:21171165

Programmable Matter Creating Systems that Can Think, Talk, and Morph Autonomously. Phase 2

DTIC Science & Technology

2011-09-13

irradiation. SWNTs have a well-defined near-IR optical absorption, specifically ideal for biocompatible devices such as drug delivery mediums or biological...investigated as follows: • Lower Critical Transition Temperature(LCST) of the CNT-pNIPAM composites. • Strain change of CNT-pNIPAM hydrogel at LCST...loading at concentrations of 0.75mg/mL, we demonstrate up to 5 times enhancement to the thermal response time of the nanotube- pNIPAM hydrogel

The role of polyglutamine expansion and protein context in disease-related huntingtin/lipid interactions

NASA Astrophysics Data System (ADS)

Burke, Kathleen Anne

Huntington's Disease (HD) is a neurodegenerative disorder that is defined by the accumulation of nanoscale aggregates comprised of the huntingtin (htt) protein. Aggregation is directly caused by an expanded polyglutamine (polyQ) domain in htt, leading to a diverse population of aggregate species, such as oligomers, fibrils, and annular aggregates. Furthermore, the length of this polyQ domain is directly related to onset and severity of disease. The first 17 amino acids on the N-terminus (N17) and the polyproline domain on the C-terminal side of the polyQ domain have been shown to further modulate the aggregation process. Additionally, N17 appears to have lipid binding properties as htt interacts with a variety of membrane-containing structures present in cells, such as organelles, and interactions with these membrane surfaces may further modulate htt aggregation. To investigate the interaction between htt exon1 and lipid bilayers, in situ atomic force microscopy (AFM) was used to directly monitor the aggregation of htt exon1 constructs with varying Q-length (35Q, 46Q, 51Q, and myc- 53Q) or synthetic peptides with different polyQ domain flanking sequences (KK-Q35-KK, KK-Q 35-P10-KK, N17-Q35-KK, and N 17-Q35-P10-KK) on supported lipid membranes comprised of total brain lipid extract. The exon1 fragments accumulated on the lipid membranes, causing disruption of the membrane, in a polyQ dependent manner. By adding N-terminal tags to the htt exon1 fragments, the interaction with the lipid bilayer was impeded. The KK-Q35-KK and KK-Q 35-P10-KK peptides had no appreciable interaction with lipid bilayers. Interestingly, polyQ peptides with the N17 flanking sequence interacted with the bilayer. N17-Q35-KK formed discrete aggregates on the bilayer, but there was minimal membrane disruption. The N17-Q35-P10-KK peptide interacted more aggressively with the lipid bilayer in a manner reminiscent of the htt exon1 proteins.

PH Sensitive WO3-Based Microelectrochemical Transistors.

DTIC Science & Technology

1986-09-22

molecular electronics, microelectrochemistr microelectrodes, sur ace modtfication, molecule-based transistors, .... " polyaniline , poly-3-methylthiophene...polypyrrole,8 poly(N-methyl pyrrole),8b polyaniline , 9 or poly(3-methylthiophene),1 0 the polymer- ’-p2 ’ -p " ; , Q ’ , : ’ ’ ’ ... , , ’ i connected...VD. Polypyrrole, 8 polyaniline , 9 and poly(3-methylthiophene)1 0 are similar in that they are conducting when oxidized, and transistors based on these

Reduced graphene oxide composites with water soluble copolymers having tailored lower critical solution temperatures and unique tube-like structure

NASA Astrophysics Data System (ADS)

Namvari, Mina; Biswas, Chandra S.; Galluzzi, Massimiliano; Wang, Qiao; Du, Bing; Stadler, Florian J.

2017-03-01

Nanohybrids of graphene with water soluble polymer were synthesized using ‘grafting from’ method. GO, prepared by modified Hummers’ method, was first reacted with sodium azide. Alkyne-terminated RAFT-CTA was synthesized by reaction of propargyl alcohol and S-1-dodecyl-S’-(α,α‘-dimethyl-α”-acetic acid) trithiocarbonate. RAFT-CTA was grafted onto the GO sheets by facile click-reaction and subsequently, N-isopropylacrylamide (NIPAM) and N-ethyleacrylamide (NEAM) were polymerized on graphene sheets via RAFT polymerization method. The respective copolymers with different ratios were also prepared. The nanohybrids were characterized by FTIR, XRD, TGA, Raman, SEM, and AFM. Both SEM and AFM clearly showed rod-like structures for rGO-PNEAM. XRD showed a small peak at 2θ = 19.21°, corresponding to d-spacing ≈ 4.6 Å. In addition, the nanohybrids showed a very broad temperature range for the LCST in water between ca. 30 and 70 °C.

Photoswitchable Layer-by-Layer Coatings Based on Photochromic Polynorbornenes Bearing Spiropyran Side Groups.

PubMed

Campos, Paula P; Dunne, Aishling; Delaney, Colm; Moloney, Cara; Moulton, Simon E; Benito-Lopez, Fernando; Ferreira, Marystela; Diamond, Dermot; Florea, Larisa

2018-04-10

Herein, we present the synthesis of linear photochromic norbornene polymers bearing spiropyran side groups (poly(SP-R)) and their assembly into layer-by-layer (LbL) films on glass substrates when converted to poly(MC-R) under UV irradiation. The LbL films were composed of bilayers of poly(allylamine hydrochloride) (PAH) and poly(MC-R), forming (PAH/poly(MC-R)) n coatings. The merocyanine (MC) form presents a significant absorption band in the visible spectral region, which allowed tracking of the LbL deposition process by UV-vis spectroscopy, which showed a linear increase of the characteristic MC absorbance band with increasing number of bilayers. The thickness and morphology of the (PAH/poly(MC-R)) n films were characterized by ellipsometry and scanning electron microscopy, respectively, with a height of ∼27.5 nm for the first bilayer and an overall height of ∼165 nm for the (PAH/poly(MC-R)) 5 multilayer film. Prolonged white light irradiation (22 h) resulted in a gradual decrease of the MC band by 90.4 ± 2.9% relative to the baseline, indicating the potential application of these films as coatings for photocontrolled delivery systems.

Experimental study of three-dimensional fin-channel charge trapping flash memories with titanium nitride and polycrystalline silicon gates

NASA Astrophysics Data System (ADS)

Liu, Yongxun; Matsukawa, Takashi; Endo, Kazuhiko; O'uchi, Shinichi; Tsukada, Junichi; Yamauchi, Hiromi; Ishikawa, Yuki; Mizubayashi, Wataru; Morita, Yukinori; Migita, Shinji; Ota, Hiroyuki; Masahara, Meishoku

2014-01-01

Three-dimensional (3D) fin-channel charge trapping (CT) flash memories with different gate materials of physical-vapor-deposited (PVD) titanium nitride (TiN) and n+-polycrystalline silicon (poly-Si) have successfully been fabricated by using (100)-oriented silicon-on-insulator (SOI) wafers and orientation-dependent wet etching. Electrical characteristics of the fabricated flash memories including statistical threshold voltage (Vt) variability, endurance, and data retention have been comparatively investigated. It was experimentally found that a larger memory window and a deeper erase are obtained in PVD-TiN-gated metal-oxide-nitride-oxide-silicon (MONOS)-type flash memories than in poly-Si-gated poly-Si-oxide-nitride-oxide-silicon (SONOS)-type memories. The larger memory window and deeper erase of MONOS-type flash memories are contributed by the higher work function of the PVD-TiN metal gate than of the n+-poly-Si gate, which is effective for suppressing electron back tunneling during erase operation. It was also found that the initial Vt roll-off due to the short-channel effect (SCE) is directly related to the memory window roll-off when the gate length (Lg) is scaled down to 46 nm or less.

Effects of P3HT concentration on the electrical properties of the Au/PEDOT:PSS/P3HT/n-GaN hybrid junction structure

NASA Astrophysics Data System (ADS)

Noh, Ji-yeon; Lee, Ha Young; Lim, Kyung-won; Ahn, Hyung Soo; Yi, Sam Nyung; Jeon, Hunsoo; Shin, Min Jeong; Yu, Young Moon; Ha, Dong Han

2017-09-01

An inorganic-organic hybrid junction has been fabricated by spin coating the p-type poly(3- hexylthiophene-2,5-diyl)(P3HT) and poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT: PSS) on an n-type GaN layer. The GaN layer was formed on Al2O3 by metal organic chemical vapor deposition(MOCVD) method. To investigate the effects of P3HT concentration on the electrical properties, we changed P3HT solution concentration and speed of spin coater. The currentvoltage (I-V ) characteristic of Au/PEDOT:PSS/P3HT/n-GaN shows rectifying behavior. The I-V characteristic was examined in the frame work of the thermionic emission model. The most proper rectifying behavior was obtained for 0.6 wt% and thickness below 65 nm of P3HT used diode. We expect that such hybrid structures, suitably developed, might be enable the fabrication of highquality electronic and optoelectronic devices.

Highly stable and degradable multifunctional microgel for self-regulated insulin delivery under physiological conditions

NASA Astrophysics Data System (ADS)

Zhang, Xinjie; Lü, Shaoyu; Gao, Chunmei; Chen, Chen; Zhang, Xuan; Liu, Mingzhu

2013-06-01

The response to glucose, pH and temperature, high drug loading capacity, self-regulated drug delivery and degradation in vivo are simultaneously probable by applying a multifunctional microgel under a rational design in a colloid chemistry method. Such multifunctional microgels are fabricated with N-isopropylacrylamide (NIPAAm), (2-dimethylamino)ethyl methacrylate (DMAEMA) and 3-acrylamidephenylboronic acid (AAPBA) through a precipitation emulsion method and cross-linked by reductive degradable N,N'-bis(arcyloyl)cystamine (BAC). This novel kind of microgel with a narrow size distribution (~250 nm) is suitable for diabetes because it can adapt to the surrounding medium of different glucose concentrations over a clinically relevant range (0-20 mM), control the release of preloaded insulin and is highly stable under physiological conditions (pH 7.4, 0.15 M NaCl, 37 °C). When synthesized multifunctional microgels regulate drug delivery, they gradually degrade as time passes and, as a result, show enhanced biocompatibility. This exhibits a new proof-of-concept for diabetes treatment that takes advantage of the properties of each building block from a multifunctional micro-object. These highly stable and versatile multifunctional microgels have the potential to be used for self-regulated therapy and monitoring of the response to treatment, or even simultaneous diagnosis as nanobiosensors.The response to glucose, pH and temperature, high drug loading capacity, self-regulated drug delivery and degradation in vivo are simultaneously probable by applying a multifunctional microgel under a rational design in a colloid chemistry method. Such multifunctional microgels are fabricated with N-isopropylacrylamide (NIPAAm), (2-dimethylamino)ethyl methacrylate (DMAEMA) and 3-acrylamidephenylboronic acid (AAPBA) through a precipitation emulsion method and cross-linked by reductive degradable N,N'-bis(arcyloyl)cystamine (BAC). This novel kind of microgel with a narrow size distribution (~250 nm) is suitable for diabetes because it can adapt to the surrounding medium of different glucose concentrations over a clinically relevant range (0-20 mM), control the release of preloaded insulin and is highly stable under physiological conditions (pH 7.4, 0.15 M NaCl, 37 °C). When synthesized multifunctional microgels regulate drug delivery, they gradually degrade as time passes and, as a result, show enhanced biocompatibility. This exhibits a new proof-of-concept for diabetes treatment that takes advantage of the properties of each building block from a multifunctional micro-object. These highly stable and versatile multifunctional microgels have the potential to be used for self-regulated therapy and monitoring of the response to treatment, or even simultaneous diagnosis as nanobiosensors. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr00835e

Design and synthesis study of the thermo-sensitive poly (N-vinylpyrrolidone-b- N, N-diethylacrylamide).

PubMed

Zhang, Xiayun; Yang, Zhongduo; Xie, Dengmin; Liu, Donglei; Chen, Zhenbin; Li, Ke; Li, Zhizhong; Tichnell, Brandon; Liu, Zhen

2018-01-01

The reversible addition fragmentation chain transfer (RAFT) polymerization method was adopted here to prepare a series of thermo-sensitive copolymers, poly (N,N-diethyl- acrylamide-b-N-vinylpyrrolidone). Their structures, molecular weight distribution and temperature sensitivity performances were characterized by the nuclear magnetic resonance ( 1 HNMR), the gel permeation chromatography (GPC) and the fluorescence spectrophotometer, respectively. It has been identified that the synthesis reaction of the block copolymer was living polymerization. The thermo-sensitivity study suggested that N-vinylpyrrolidone (NVP), played a key role on the lower critical solution temperature (LCST) performance.

Formation of cage-like particles by poly(amino acid)-based block copolymers in aqueous solution.

PubMed Central

Cudd, A; Bhogal, M; O'Mullane, J; Goddard, P

1991-01-01

When dissolved in N,N-dimethylformamide and then dialyzed against phosphate-buffered saline, A-B-A block copolymers composed of poly [N5-(2-hydroxyethyl)-L-glutamine]-block-poly(gamma-benzyl-L-glutamate)- block-poly [N5-(2-hydroxyethyl)-L-glutamine] form particles. The particles are cage-like structures with average diameters of 300 nm (average polydispersity, 0.3-0.5). They are stable in aqueous solution at 4 degrees C for up to 3 weeks, at which time flocculation becomes apparent. Negative staining and freeze-fracture electron microscopy suggest that cage-like particles are formed by selective association of segregated micelle populations. A model of particle formation is presented in which B blocks form micelles in dimethylformamide. On dialysis against an aqueous solution, the extended A blocks then associate intermolecularly to form rod-shaped micelles, which connect the B block micelles. The result is a meshed cage-like particle. The implications of these observations on the aggregation behavior of polymeric surfactants in dilute solution are discussed. Images PMID:11607245

Characterization of nanometer-thick polycrystalline silicon with phonon-boundary scattering enhanced thermoelectric properties and its application in infrared sensors.

PubMed

Zhou, Huchuan; Kropelnicki, Piotr; Lee, Chengkuo

2015-01-14

Although significantly reducing the thermal conductivity of silicon nanowires has been reported, it remains a challenge to integrate silicon nanowires with structure materials and electrodes in the complementary metal-oxide-semiconductor (CMOS) process. In this paper, we investigated the thermal conductivity of nanometer-thick polycrystalline silicon (poly-Si) theoretically and experimentally. By leveraging the phonon-boundary scattering, the thermal conductivity of 52 nm thick poly-Si was measured as low as around 12 W mK(-1) which is only about 10% of the value of bulk single crystalline silicon. The ZT of n-doped and p-doped 52 nm thick poly-Si was measured as 0.067 and 0.024, respectively, while most previously reported data had values of about 0.02 and 0.01 for a poly-Si layer with a thickness of 0.5 μm and above. Thermopile infrared sensors comprising 128 pairs of thermocouples made of either n-doped or p-doped nanometer-thick poly-Si strips in a series connected by an aluminium (Al) metal interconnect layer are fabricated using microelectromechanical system (MEMS) technology. The measured vacuum specific detectivity (D*) of the n-doped and p-doped thermopile infrared (IR) sensors are 3.00 × 10(8) and 1.83 × 10(8) cm Hz(1/2) W(-1) for sensors of 52 nm thick poly-Si, and 5.75 × 10(7) and 3.95 × 10(7) cm Hz(1/2) W(-1) for sensors of 300 nm thick poly-Si, respectively. The outstanding thermoelectric properties indicate our approach is promising for diverse applications using ultrathin poly-Si technology.

Synthesis and Characterization of New Phosphazene Polymers.

DTIC Science & Technology

1988-01-21

reaction of a poly( alkyl /arylphosphazene). In this study, one-half of the methyl groups in [Ph(Me)PN]n (chosen for its solubility in THF as opposed to...polymerization reaction ; and (5) the derivative chemistry of the preformed poly( alkyl /arylphosphazenes)., Synthesis of Poly( alkyl /arylphosphazenes) SC A... vessels , these phosphoranimines quantitatively eliminate the silyl ether byproduct, Me3SiOCH2CF 3 , to form the poly( alkyl /arylphosphazenes). The synthesis

Azide functionalized poly(3-hexylthiophene) and method of forming same

DOEpatents

Qin, Yang; Grubbs, Robert B; Park, Young Suk

2014-03-25

The invention relates azide functionalized poly(3-hexylthiophene)s. Various azide functionalized poly(3-hexylthiophene)s and intermediates are disclosed and described, as well as method for making novel monomers that are synthesized and transformed into P3HT-N.sub.mp for use as organic conducting polymers in organic photovoltaic devices.

Enzymatic modification of natural and synthetic polymers using lipases and proteases

NASA Astrophysics Data System (ADS)

Chakraborty, Soma

Enzymatic modification of natural/synthetic polymers [starch nanoparticles, poly (n-alkyl acrylates) and poly(vinyl formamide)] was studied. Enzymes used for catalysis were lipases and proteases. Starch nanoparticles (40nm diameter) were incorporated into AOT-coated reverse micelles. Reactions performed with the acylating agents vinyl stearate, epsilon-caprolactone and maleic anhydride in toluene in presence of Novozyme-435 at 40°C for 36h gave products with degrees of substitution of 0.8, 0.6 and 0.4 respectively. DEPT-135 NMR spectra revealed that the modification occurred regioselectively at the C-6 position of the glucose units. Infrared microspectroscopy showed that the surfactant coated starch nanoparticles diffuse into pores of Novozyme-435 beads, coming in close proximity with CALB to promote modification. The modified products retained nanoscale dimensions. Catalysis of amide bond formation between a low molar mass amine and ester side groups of poly(n-alkyl acrylates)[poly(ethyl acrylate), poly(methyl acrylate) and poly(butyl acrylate)] was also examined. The nucleophiles were mono and diamines. Among the poly(n-alkyl acrylates) and the lipases studied, poly(ethyl acrylate) was the preferred substrate and Novozyme-435 the most active lipase. Poly(ethyl acrylate) in 80% by-volume toluene was reacted with 1 equivalent per repeat unit of hexyl amine at 70°C in presence of Novozyme-435. The product contained 10.6 mol% amide groups. Attempts to increase the amidation beyond 10--11 mol% by increasing the reaction time or use of fresh enzyme were unsuccessful, showing that poly(ethylacrylate-co-10mol%hexylacrylamide) is a poor substrate for further acylation. When chiral amines ([R,S]-alpha-methyl benzylamine, [R,S]-beta-methyl phenyl amine) were used as nucleophiles, Novozyme-435 enantioselectively catalyzed amidation of poly(ethyl acrylate). Poly(vinyl formamide), P(VfAm) by acid or base-catalyzed hydrolysis leads to poly(vinylamine), P(VAm), and corresponding copolymers. As an alternative to chemical hydrolysis a mild and selective enzymatic method was discovered. Fifteen proteases were evaluated for this transformation. Of these, PROT 7 was the most active. Within 24h PROT 7 gave products with 44% hydrolysis. Further hydrolysis was not observed by extending the reaction time because poly(vinylformamide-co-40%vinylamine) is a poor substrate for further hydrolysis. The sequence distribution of copolymers formed by chemical hydrolysis and enzymatic hydrolysis was compared. Chemical hydrolysis gave random copolymer. In contrast, PROT 7 gave block-like arrangement of VAm units.

Glucose Oxidase Adsorption on Sequential Adsorbed Polyelectrolyte Films Studied by Spectroscopic Techniques

NASA Astrophysics Data System (ADS)

Tristán, Ferdinando; Solís, Araceli; Palestino, Gabriela; Gergely, Csilla; Cuisinier, Frédéric; Pérez, Elías

2005-04-01

The adsorption of Glucose Oxidase (GOX) on layers of poly(allylamine hydrochloride) (PAH) and poly(acrylic acid) (PAA) deposited on Sequentially Adsorbed Polyelectrolyte Films (SAPFs) were studied by three different spectroscopic techniques. These techniques are: Optical Wave Light Spectroscopy (OWLS) to measure surface density; Fluorescence Resonance Energy Transfer (FRET) to verify the adsorption of GOX on the surface; and Fourier Transform Infrared Spectroscopy in Attenuated Total Reflection mode (FTIR-HATR) to inspect local structure of polyelectrolytes and GOX. Two positive and two negative polyelectrolytes are used: Cationic poly(ethyleneimine) (PEI) and poly(allylamine hydrochloride) (PAH) and anionic poly(sodium 4-styrene sulfonate) (PSS) and poly(acrylic acid) (PAA). These spectroscopic techniques do not require any labeling for GOX or SAPFs, specifically GOX and PSS are naturally fluorescent and are used as a couple donor-acceptor for the FRET technique. The SAPFs are formed by a (PEI)-(PSS/PAH)2 film followed by (PAA/PAH)n bilayers. GOX is finally deposited on top of SAPFs at different values of n (n=1..5). Our results show that GOX is adsorbed on positive ended SAPFs forming a monolayer. Contrary, GOX adsorption is not observed on negative ended film polyelectrolyte. GOX stability was tested adding a positive and a negative polyelectrolyte after GOX adsorption. Protein is partially removed by PAH and PAA, with lesser force by PAA.

Effect of diblock copolymer properties on the photophysical properties of dendrimer silicon phthalocyanine nanoconjugates

NASA Astrophysics Data System (ADS)

Chen, Kuizhi; Pan, Sujuan; Zhuang, Xuemei; Lv, Hafei; Que, Shoulin; Xie, Shusen; Yang, Hongqin; Peng, Yiru

2016-07-01

1-2 generation poly(benzyl aryl ether) dendrimer silicon phthalocyanines with axially disubstituted cyano terminal functionalities (G n -DSiPc(CN)4 n , (G n = n-generation dendrimer, n = 1-2)) were synthesized. Their structures were characterized by elemental analysis, IR, 1H NMR, and ESI-MS. Polymeric nanoparticles (G n -DSiPc(CN)4 n /m) were formed through encapsulating G n -DSiPc(CN)4 n into three monomethoxyl poly(ethylene glycol)-poly(ɛ-caprolactone) diblock copolymers (MPEG-PCL) with different hydrophilic/hydrophobic proportion, respectively. The effect of dendritic generation and the hydrophilic/hydrophobic proportion of diblock copolymers on the UV/Vis and fluorescence spectra of G n -DSiPc(CN)4 n and G n -DSiPc(CN)4 n /m were studied. The photophysical properties of polymeric nanoparticles exhibited dendritic generation and hydrophilic/hydrophobic proportion dependence. The fluorescence intensities and lifetimes of G n -DSiPc(CN)4 n /m were lower than the corresponding free dendrimer phthalocyanines. G n -DSiPc(CN)4 n encapsulated into MPEG-PCL with hydrophilic/hydrophobic molecular weight ratio 2000:4000 exhibited excellent photophysical property. The mean diameter of MPEG2000-PCL2000 micelles was about 70 nm, which decreased when loaded with G n -DSiPc(CN)4 n .

Synthesis, characterization, and morphology study of poly(acrylamide-co-acrylic acid)-grafted-poly(styrene-co-methyl methacrylate) "raspberry"-shape like structure microgels by pre-emulsified semi-batch emulsion polymerization.

PubMed

Ramli, Ros Azlinawati; Hashim, Shahrir; Laftah, Waham Ashaier

2013-02-01

A novel microgels were polymerized using styrene (St), methyl methacrylate (MMA), acrylamide (AAm), and acrylic acid (AAc) monomers in the presence of N,N'-methylenebisacrylamide (MBA) cross-linker. Pre-emulsified monomer was first prepared followed by polymerizing monomers using semi-batch emulsion polymerization. Fourier Transform Infrared Spectroscopy (FTIR) and (1)H Nuclear Magnetic Resonance (NMR) were used to determine the chemical structure and to indentify the related functional group. Grafting and cross-linking of poly(acrylamide-co-acrilic acid)-grafted-poly(styrene-co-methyl methacrylate) [poly(AAm-co-AAc)-g-poly(St-co-MMA)] microgels are approved by the disappearance of band at 1300 cm(-1), 1200 cm(-1) and 1163 cm(-1) of FTIR spectrum and the appearance of CH peaks at 5.5-5.7 ppm in (1)H NMR spectrum. Scanning Electron Microscope (SEM) images indicated that poly(St-co-MMA) particle was lobed morphology coated by cross-linked poly(AAm-co-AAc) shell. Furthermore, SEM results revealed that poly(AAm-co-AAc)-g-poly(St-co-MMA) is composite particle that consist of "raspberry"-shape like structure core. Internal structures of the microgels showed homogeneous network of pores, an extensive interconnection among pores, thicker pore walls, and open network structures. Water absorbency test indicated that the sample with particle size 0.43 μm had lower equilibrium water content, % than the sample with particle size 7.39 μm. Copyright © 2012 Elsevier Inc. All rights reserved.

Bespoke contrast-matched diblock copolymer nanoparticles enable the rational design of highly transparent Pickering double emulsions

NASA Astrophysics Data System (ADS)

Rymaruk, Matthew J.; Thompson, Kate L.; Derry, Matthew J.; Warren, Nicholas J.; Ratcliffe, Liam P. D.; Williams, Clive N.; Brown, Steven L.; Armes, Steven P.

2016-07-01

We report the preparation of highly transparent oil-in-water Pickering emulsions using contrast-matched organic nanoparticles. This is achieved via addition of judicious amounts of either sucrose or glycerol to an aqueous dispersion of poly(glycerol monomethacrylate)56-poly(2,2,2-trifluoroethyl methacrylate)500 [PGMA-PTFEMA] diblock copolymer nanoparticles prior to high shear homogenization with an equal volume of n-dodecane. The resulting Pickering emulsions comprise polydisperse n-dodecane droplets of 20-100 μm diameter and exhibit up to 96% transmittance across the visible spectrum. In contrast, control experiments using non-contrast-matched poly(glycerol monomethacrylate)56-poly(benzyl methacrylate)300 [PGMA56-PBzMA300] diblock copolymer nanoparticles as a Pickering emulsifier only produced conventional highly turbid emulsions. Thus contrast-matching of the two immiscible phases is a necessary but not sufficient condition for the preparation of highly transparent Pickering emulsions: it is essential to use isorefractive nanoparticles in order to minimize light scattering. Furthermore, highly transparent oil-in-water-in-oil Pickering double emulsions can be obtained by homogenizing the contrast-matched oil-in-water Pickering emulsion prepared using the PGMA56-PTFEMA500 nanoparticles with a contrast-matched dispersion of hydrophobic poly(lauryl methacrylate)39-poly(2,2,2-trifluoroethyl methacrylate)800 [PLMA39-PTFEMA800] diblock copolymer nanoparticles in n-dodecane. Finally, we show that an isorefractive oil-in-water Pickering emulsion enables fluorescence spectroscopy to be used to monitor the transport of water-insoluble small molecules (pyrene and benzophenone) between n-dodecane droplets. Such transport is significantly less efficient than that observed for the equivalent isorefractive surfactant-stabilized emulsion. Conventional turbid emulsions do not enable such a comparison to be made because the intense light scattering leads to substantial spectral attenuation.We report the preparation of highly transparent oil-in-water Pickering emulsions using contrast-matched organic nanoparticles. This is achieved via addition of judicious amounts of either sucrose or glycerol to an aqueous dispersion of poly(glycerol monomethacrylate)56-poly(2,2,2-trifluoroethyl methacrylate)500 [PGMA-PTFEMA] diblock copolymer nanoparticles prior to high shear homogenization with an equal volume of n-dodecane. The resulting Pickering emulsions comprise polydisperse n-dodecane droplets of 20-100 μm diameter and exhibit up to 96% transmittance across the visible spectrum. In contrast, control experiments using non-contrast-matched poly(glycerol monomethacrylate)56-poly(benzyl methacrylate)300 [PGMA56-PBzMA300] diblock copolymer nanoparticles as a Pickering emulsifier only produced conventional highly turbid emulsions. Thus contrast-matching of the two immiscible phases is a necessary but not sufficient condition for the preparation of highly transparent Pickering emulsions: it is essential to use isorefractive nanoparticles in order to minimize light scattering. Furthermore, highly transparent oil-in-water-in-oil Pickering double emulsions can be obtained by homogenizing the contrast-matched oil-in-water Pickering emulsion prepared using the PGMA56-PTFEMA500 nanoparticles with a contrast-matched dispersion of hydrophobic poly(lauryl methacrylate)39-poly(2,2,2-trifluoroethyl methacrylate)800 [PLMA39-PTFEMA800] diblock copolymer nanoparticles in n-dodecane. Finally, we show that an isorefractive oil-in-water Pickering emulsion enables fluorescence spectroscopy to be used to monitor the transport of water-insoluble small molecules (pyrene and benzophenone) between n-dodecane droplets. Such transport is significantly less efficient than that observed for the equivalent isorefractive surfactant-stabilized emulsion. Conventional turbid emulsions do not enable such a comparison to be made because the intense light scattering leads to substantial spectral attenuation. Electronic supplementary information (ESI) available: GPC chromatograms, additional transmission electron micrographs, digital photographs, visible absorption spectra and laser diffraction data, further optical and fluorescence micrographs. See DOI: 10.1039/c6nr03856e

New Poly(amide-imide)/Nanocomposites Reinforced Silicate Nanoparticles Based on N-pyromellitimido-L-phenyl Alanine Containing Ether Moieties

NASA Astrophysics Data System (ADS)

Faghihi, Khalil; Shabanian, Meisam; Dadfar, Ehsan

2012-02-01

A series of Poly(amide-imide)/montmorillonite nanocomposites containing N-pyromellitimido-L-phenyl alanine moiety in the main chain were synthesized by a convenient solution intercalation technique. Poly(amide-imide) (PAI) 5 as a source of polymer matrix was synthesized by the direct polycondensation reaction of N-pyromellitimido-L-phenyl alanine 3 with 4,4'-diamino diphenyl ether 4 in the presence of triphenyl phosphite (TPP), CaCl2, pyridine and N-methyl-2-pyrrolidone (NMP). The resulting nanocomposite films were characterized by Fourier transform infrared spectra (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). The results showed that organo-modified clay was dispersed homogeneously in PAI matrix. TGA indicated an enhancement of thermal stability of new nanocomposites compared with the pure polymer.

Evaluation of the Protective Efficacy of Poly I:C as an Adjuvant for H9N2 Subtype Avian Influenza Inactivated Vaccine and Its Mechanism of Action in Ducks.

PubMed

Zhang, Aiguo; Lai, Hanzhang; Xu, Jiahua; Huang, Wenke; Liu, Yufu; Zhao, Dawei; Chen, Ruiai

2017-01-01

Current commercial H9 avian influenza vaccines cannot provide satisfactory protective immunity against antigenic variant influenza viruses in ducks. Poly I:C, when used as an adjuvant, improves humoral and cellular immunity in many animals but has not been tested in ducks. In this study, we investigated the protective efficacy of Poly I:C as an adjuvant for an inactivated H9N2 Avian influenza vaccine in ducks. We found that an H9N2 vaccine administered with poly I:C (H9-PIC vaccine) induced a significantly more rapid response with higher anti-influenza antibody titers than those of the vaccine alone (H9 vaccine). Moreover, virus shedding was reduced in ducks immunized with the H9-PIC vaccine after challenge with an H9 subtype antigenic variant viruses. IFN-α, IFN-γ, IL-6 and MHC-II mRNA levels were all elevated in ducks receiving the H9-PIC vaccine. In addition, lower expression level of MHC-I may be a reason for inefficient protective ability against heterologous influenza viruses in H9-PIC vaccination of ducks. In conclusion, poly I:C adjuvant enhanced both humoral and cellular immune responses in ducks induced by immunization of inactivated H9N2 vaccine.

Evaluation of the Protective Efficacy of Poly I:C as an Adjuvant for H9N2 Subtype Avian Influenza Inactivated Vaccine and Its Mechanism of Action in Ducks

PubMed Central

Zhang, Aiguo; Lai, Hanzhang; Xu, Jiahua; Huang, Wenke; Liu, Yufu; Zhao, Dawei; Chen, Ruiai

2017-01-01

Current commercial H9 avian influenza vaccines cannot provide satisfactory protective immunity against antigenic variant influenza viruses in ducks. Poly I:C, when used as an adjuvant, improves humoral and cellular immunity in many animals but has not been tested in ducks. In this study, we investigated the protective efficacy of Poly I:C as an adjuvant for an inactivated H9N2 Avian influenza vaccine in ducks. We found that an H9N2 vaccine administered with poly I:C (H9-PIC vaccine) induced a significantly more rapid response with higher anti-influenza antibody titers than those of the vaccine alone (H9 vaccine). Moreover, virus shedding was reduced in ducks immunized with the H9-PIC vaccine after challenge with an H9 subtype antigenic variant viruses. IFN-α, IFN-γ, IL-6 and MHC-II mRNA levels were all elevated in ducks receiving the H9-PIC vaccine. In addition, lower expression level of MHC-I may be a reason for inefficient protective ability against heterologous influenza viruses in H9-PIC vaccination of ducks. In conclusion, poly I:C adjuvant enhanced both humoral and cellular immune responses in ducks induced by immunization of inactivated H9N2 vaccine. PMID:28135294