Development of a binary carrier system consisting polyethylene glycol 4000 - ethyl cellulose for ibuprofen solid dispersion

PubMed Central

Alagdar, Gada Sulaiman A.; Oo, May Kyaw; Sengupta, Pinaki; Mandal, Uttam Kumar; Jaffri, Julian Md.; Chatterjee, Bappaditya

2017-01-01

Background and Objective: One of the established strategies to improve solubility and dissolution rate of poorly water-soluble drugs is solid dispersion (SD). Polyethylene glycol (PEG) is used as common carrier despite its stability problem which may be overcome by the addition of hydrophobic polymer. The present research aimed to develop an SD formulation with ibuprofen, a poor water-soluble BCS Class II drug as active pharmaceutical ingredient (API) and PEG 4000-ethyl cellulose (EC) as binary carrier. Methods: Melt mixing SD method was employed using a ratio of API: binary carrier (1:3.5 w/w) (SDPE). Another SD was prepared using only PEG (SDP) as a carrier for comparative study. The developed formulation was evaluated using optical microscopy, scanning electron microscopy (SEM), determination of moisture content, differential scanning calorimetry (DSC), in vitro dissolution test, attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and flow properties. Results: SEM and DSC indicated the conversion of crystalline ibuprofen to fine partly amorphous solid dispersion, which was responsible for the increase in dissolution rate of SD than a physical mixture. The release characteristics within 1 h from the higher to the lower value were the SDPE> SDP> physical mixture. Flow property evaluation using the angle of repose showed no difference between SD and PM. However, by Carr index and Hausner ratio, the flow properties of SDPE was excellent. Conclusion: The SD formulation with the PEG 4000-EC carrier can be effective to enhance in vitro dissolution of ibuprofen immediate release dosage form. PMID:29184827

El administrador Pruitt anuncia $54.3 millones en subvenciones Brownfields para evaluar y limpiar las propiedades contaminadas y promover el redesarrollo económico a nivel nacional

EPA Pesticide Factsheets

Comunicado de prensa de la EPA: El administrador Pruitt anuncia $54.3 millones en subvenciones Brownfields para evaluar y limpiar las propiedades contaminadas y promover el redesarrollo económico a nivel nacional

Bromelain purification through unconventional aqueous two-phase system (PEG/ammonium sulphate).

PubMed

Coelho, D F; Silveira, E; Pessoa Junior, A; Tambourgi, E B

2013-02-01

This paper focuses on the feasibility of unconventional aqueous two-phase systems for bromelain purification from pineapple processing waste. The main difference in comparison with conventional systems is the integration of the liquid-liquid extraction technique with fractional precipitation, which can decrease the protein content with no loss of biological activity by removing of unwanted molecules. The analysis of the results was based on the response surface methodology and revealed that the use of the desirability optimisation methodology (DOM) was necessary to achieve higher purification factor values and greater bromelain recovery. The use of DOM yielded an 11.80-fold purification factor and 66.38 % biological activity recovery using poly(ethylene glycol) (PEG) with a molar mass of 4,000, 10.86 % PEG concentration (m/m) and 36.21 % saturation of ammonium sulphate.

Calculation of NaCl, KCl and LiCl Salts Activity Coefficients in Polyethylene Glycol (PEG4000)-Water System Using Modified PHSC Equation of State, Extended Debye-Hückel Model and Pitzer Model

NASA Astrophysics Data System (ADS)

Marjani, Azam

2016-07-01

For biomolecules and cell particles purification and separation in biological engineering, besides the chromatography as mostly applied process, aqueous two-phase systems (ATPS) are of the most favorable separation processes that are worth to be investigated in thermodynamic theoretically. In recent years, thermodynamic calculation of ATPS properties has attracted much attention due to their great applications in chemical industries such as separation processes. These phase calculations of ATPS have inherent complexity due to the presence of ions and polymers in aqueous solution. In this work, for target ternary systems of polyethylene glycol (PEG4000)-salt-water, thermodynamic investigation for constituent systems with three salts (NaCl, KCl and LiCl) has been carried out as PEG is the most favorable polymer in ATPS. The modified perturbed hard sphere chain (PHSC) equation of state (EOS), extended Debye-Hückel and Pitzer models were employed for calculation of activity coefficients for the considered systems. Four additional statistical parameters were considered to ensure the consistency of correlations and introduced as objective functions in the particle swarm optimization algorithm. The results showed desirable agreement to the available experimental data, and the order of recommendation of studied models is PHSC EOS > extended Debye-Hückel > Pitzer. The concluding remark is that the all the employed models are reliable in such calculations and can be used for thermodynamic correlation/predictions; however, by using an ion-based parameter calculation method, the PHSC EOS reveals both reliability and universality of applications.

Optical tweezers reveal force plateau and internal friction in PEG-induced DNA condensation.

PubMed

Ojala, Heikki; Ziedaite, Gabija; Wallin, Anders E; Bamford, Dennis H; Hæggström, Edward

2014-03-01

The simplified artificial environments in which highly complex biological systems are studied do not represent the crowded, dense, salty, and dynamic environment inside the living cell. Consequently, it is important to investigate the effect of crowding agents on DNA. We used a dual-trap optical tweezers instrument to perform force spectroscopy experiments at pull speeds ranging from 0.3 to 270 μm/s on single dsDNA molecules in the presence of poly(ethylene glycol) (PEG) and monovalent salt. PEG of sizes 1,500 and 4,000 Da condensed DNA, and force-extension data contained a force plateau at approximately 1 pN. The level of the force plateau increased with increasing pull speed. During slow pulling the dissipated work increased linearly with pull speed. The calculated friction coefficient did not depend on amount of DNA incorporated in the condensate, indicating internal friction is independent of the condensate size. PEG300 had no effect on the dsDNA force-extension curve. The force plateau implies that condensation induced by crowding agents resembles condensation induced by multivalent cations.

PEG and mPEG-anthracene induce DNA condensation and particle formation.

PubMed

Froehlich, E; Mandeville, J S; Arnold, D; Kreplak, L; Tajmir-Riahi, H A

2011-08-18

In this study, we investigated the binding of DNA with poly(ethylene glycol) (PEG) of different sizes and compositions such as PEG 3350, PEG 6000, and mPEG-anthracene in aqueous solution at physiological conditions. The effects of size and composition on DNA aggregation and condensation as well as conformation were determined using Fourier transform infrared (FTIR), UV-visible, CD, fluorescence spectroscopic methods and atomic force microscopy (AFM). Structural analysis showed moderate complex formation for PEG 3350 and PEG 6000 and weaker interaction for mPE-anthracene-DNA adducts with both hydrophilic and hydrophobic contacts. The order of ± stability of the complexes formed is K(PEG 6000) = 1.5 (±0.4) × 10(4) M(-1) > K(PEG 3350) = 7.9 (±1) × 10(3) M(-1) > K(m(PEG-anthracene))= 3.6 (±0.8) × 10(3) M(-1) with nearly 1 bound PEG molecule per DNA. No B-DNA conformational changes were observed, while DNA condensation and particle formation occurred at high PEG concentration.

30 CFR 56.4000 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Definitions. 56.4000 Section 56.4000 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Fire Prevention and Control § 56.4000...

Synthesis of PEG-rich PLGA-PEG-PLGA for the PLGA-PEG-PLGA/laponite hydrogels with thermoresponsive sol-gel transitions

NASA Astrophysics Data System (ADS)

Tanimoto, Keishi; Maeda, Tomoki; Hotta, Atsushi

Poly (D,L-lactide-co-glycolide)-b-poly (ethylene glycol)-b-poly (D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) possesses moderate biocompatibility originating from the relatively shorter PEG block in its polymeric molecule. For the maximum utilization of the highly biocompatible PEG block, the PEG block should be relatively longer, and thus the PEG/PLGA ratio, the molecular weight ratio of PEG and PLGA, should be higher. In addition, for the wider use of PLGA-PEG-PLGA in the biological fields, the aqueous PLGA-PEG-PLGA solution should transfer from sol to gel states in response to the increase in temperature. It was reported, however, through the previous researches, that the PLGA-PEG-PLGA solution with a high PEG/PLGA ratio (above 0.5) would not exhibit thermoresponsive sol-gel transitions. In this work, PLGA-PEG-PLGAs with higher PEG/PLGA ratios were synthesized and the laponite, an inorganic nanoparticle, was added to the solutions to realize the thermoresponsive sol-gel transition. It was found that the PLGA-PEG-PLGA with the high PEG/PLGA ratio of 3.0 could exhibit the thermoresponsive sol-gel transition by adding laponite at 1.25 weight percent. The physical characteristics of the gel were also studied by the dynamic mechanical analysis (DMA) This work was supported by a Grant-in-Aid for Scientific Research (A) (No. 15H02298 to A.H.) and a Grant-in-Aid for Research Activity Start-up (No.15H06586 to T.M.) from JSPS: KAKENHI\\x9D.

Two-week aerosol inhalation study on polyethylene glycol (PEG) 3350 in F-344 rats.

PubMed

Klonne, D R; Dodd, D E; Losco, P E; Troup, C M; Tyler, T R

1989-03-01

PEGs in the 3000 to 4000 MW range are used in many pharmaceutical and cosmetic applications; they produce little ocular or dermal irritation and have extremely low acute and subchronic toxicity by oral and dermal routes of administration. However, little information exists on the potential of aerosols of these materials to produce adverse health effects. F-344 rats were exposed to aerosols of PEG 3350 (20% w:w in water) at 0, 109, 567, or 1008 (highest attainable) mg/m3 for 6 hr/d, 5 d/wk for 2 wk. No exposure-related toxicity was found with regard to clinical signs, ophthalmology, serum chemistry, urinalysis, or gross pathology. Exposure-related effects included: a 50% increase in the neutrophil count (males only) at 1008 mg/m3; decreased body weight gain (16%) for both the 567 and 1008 mg/m3 groups (males only); absolute lung weights of both sexes were increased 10 and 18% for the 567 and 1008 mg/m3 groups, respectively. A slight increase in the number of macrophages in the alveoli was the only change observed histologically in all PEG 3350-exposed groups. Therefore, inhalation of aerosols of PEG 3350 at concentrations up to 1008 mg/m3 produced relatively little toxicity in rats, the lung was the target organ, and the no-observable-effect-level was between 109 to 567 mg/m3.

Effect of The Addition of PEG and PVA Polymer for Gel Electrolytes in Dye-Sensitized Solar Cell (DSSC) with Chlorophyll as Dye Sensitizer

NASA Astrophysics Data System (ADS)

Seni, Ramadhanti S.; Puspitasari, Nurrisma; Endarko

2017-07-01

Dye-sensitized Solar Cell (DSSC) is a third-generation solar cell that consists of a working electrode, electrolyte and counter electrode. One of the most important parts of DSSC is an electrolyte that roles as a medium and regenerates the electron transport of electrons in the dye. However, the liquid electrolyte has a lack of stability in long-term use and easily evaporate or leak in DSSC. Therefore, this study aims to investigate an effect of the addition of polymer material such as PEG 1000, 4000 and PVA 60000 for fabricating a gel electrolyte to solve the problems of liquid electrolyte. The synthesized TiO2 nanoparticles used in this study was prepared using co-precipitation (CPT) method which produces TiO2 anatase phase with a crystal size of 11.1 nm. DSSC has been successfully conducted and analyzed to evaluate its performance. The results showed that the efficiency of DSSC cells using gel electrolyte prepared with PVA 60000 was better than a liquid electrolyte, PEG 1000, 4000, with the efficiency could be obtained at 0.083, 0.018, 0.033, and 0.054%, respectively. The results demonstrated that the addition PEG and/or PVA could be enhanced the performance of DSSC due to gel electrolyte produced current and voltage more stable compared to the liquid electrolyte.

12 CFR 7.4000 - Visitorial powers.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Visitorial powers. 7.4000 Section 7.4000 Banks... Preemption § 7.4000 Visitorial powers. (a) General rule. (1) Only the OCC or an authorized representative of the OCC may exercise visitorial powers with respect to national banks, except as provided in paragraph...

12 CFR 7.4000 - Visitorial powers.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 1 2011-01-01 2011-01-01 false Visitorial powers. 7.4000 Section 7.4000 Banks... Preemption § 7.4000 Visitorial powers. (a) General rule. (1) Only the OCC or an authorized representative of the OCC may exercise visitorial powers with respect to national banks, except as provided in paragraph...

Effect of PEG and mPEG-anthracene on tRNA aggregation and particle formation.

PubMed

Froehlich, E; Mandeville, J S; Arnold, D; Kreplak, L; Tajmir-Riahi, H A

2012-01-09

Poly(ethylene glycol) (PEG) and its derivatives are synthetic polymers with major applications in gene and drug delivery systems. Synthetic polymers are also used to transport miRNA and siRNA in vitro. We studied the interaction of tRNA with several PEGs of different compositions, such as PEG 3350, PEG 6000, and mPEG-anthracene under physiological conditions. FTIR, UV-visible, CD, and fluorescence spectroscopic methods as well as atomic force microscopy (AFM) were used to analyze the PEG binding mode, the binding constant, and the effects of polymer complexation on tRNA stability, aggregation, and particle formation. Structural analysis showed that PEG-tRNA interaction occurs via RNA bases and the backbone phosphate group with both hydrophilic and hydrophobic contacts. The overall binding constants of K(PEG 3350-tRNA)= 1.9 (±0.5) × 10(4) M(-1), K(PEG 6000-tRNA) = 8.9 (±1) × 10(4) M(-1), and K(mPEG-anthracene)= 1.2 (±0.40) × 10(3) M(-1) show stronger polymer-RNA complexation by PEG 6000 and by PEG 3350 than the mPEG-anthracene. AFM imaging showed that PEG complexes contain on average one tRNA with PEG 3350, five tRNA with PEG 6000, and ten tRNA molecules with mPEG-anthracene. tRNA aggregation and particle formation occurred at high polymer concentrations, whereas it remains in A-family structure.

30 CFR 57.4000 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Definitions. 57.4000 Section 57.4000 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Fire Prevention and Control § 57...

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

NASA Astrophysics Data System (ADS)

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

2013-11-01

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

12 CFR 614.4000 - Farm Credit Banks.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 6 2011-01-01 2011-01-01 false Farm Credit Banks. 614.4000 Section 614.4000 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM LOAN POLICIES AND OPERATIONS Lending Authorities § 614.4000 Farm Credit Banks. (a) Long-term real estate lending. Except to the extent such...

Size-dependent in vivo toxicity of PEG-coated gold nanoparticles

PubMed Central

Zhang, Xiao-Dong; Wu, Di; Shen, Xiu; Liu, Pei-Xun; Yang, Na; Zhao, Bin; Zhang, Hao; Sun, Yuan-Ming; Zhang, Liang-An; Fan, Fei-Yue

2011-01-01

Background Gold nanoparticle toxicity research is currently leading towards the in vivo experiment. Most toxicology data show that the surface chemistry and physical dimensions of gold nanoparticles play an important role in toxicity. Here, we present the in vivo toxicity of 5, 10, 30, and 60 nm PEG-coated gold nanoparticles in mice. Methods Animal survival, weight, hematology, morphology, organ index, and biochemistry were characterized at a concentration of 4000 μg/kg over 28 days. Results The PEG-coated gold particles did not cause an obvious decrease in body weight or appreciable toxicity even after their breakdown in vivo. Biodistribution results show that 5 nm and 10 nm particles accumulated in the liver and that 30 nm particles accumulated in the spleen, while the 60 nm particles did not accumulate to an appreciable extent in either organ. Transmission electron microscopic observations showed that the 5, 10, 30, and 60 nm particles located in the blood and bone marrow cells, and that the 5 and 60 nm particles aggregated preferentially in the blood cells. The increase in spleen index and thymus index shows that the immune system can be affected by these small nanoparticles. The 10 nm gold particles induced an increase in white blood cells, while the 5 nm and 30 nm particles induced a decrease in white blood cells and red blood cells. The biochemistry results show that the 10 nm and 60 nm PEG-coated gold nanoparticles caused a significant increase in alanine transaminase and aspartate transaminase levels, indicating slight damage to the liver. Conclusion The toxicity of PEG-coated gold particles is complex, and it cannot be concluded that the smaller particles have greater toxicity. The toxicity of the 10 nm and 60 nm particles was obviously higher than that of the 5 nm and 30 nm particles. The metabolism of these particles and protection of the liver will be more important issues for medical applications of gold-based nanomaterials in future. PMID:21976982

Differences in taste between two polyethylene glycol preparations.

PubMed

Szojda, Maria M; Mulder, Chris J J; Felt-Bersma, Richelle J F

2007-12-01

Polyethylene glycol preparations (PEG) are increasingly used for chronic constipation in both adults and children. There are some suggestions that PEG 4000 with orange flavour (Forlax) tastes better than PEG 3350 which contains salt (Movicolon). Poor taste is an important factor for non-compliance and is one of the leading causes of therapy failure. The aim of the study was to compare the taste of two commonly used PEG preparations, PEG 4000 and PEG 3350. A double-blind, cross over randomised trial. A hundred people were recruited by advertisement. All tasted both preparations without swallowing and after tasting each of the preparations, they rinsed their mouths. Then a score, on a 5-point scale, was given for both preparations. 100 volunteers were included (27 males and 73 females, mean age 36). The taste score for PEG 4000 (mean 3.9, SD 0.7) was significantly better than for PEG 3350 (mean 2.7, SD 0.7) (p<0.0001, Wilcoxon matched pairs test). No difference in gender or age was observed. The volunteers which tasted PEG 3350 liked it more, when they tasted it first rather than when they tasted it after PEG 4000 (p<0.0001). The order in which volunteers tested PEG 4000 had no influence on the taste results. PEG 4000 tastes better than PEG 3350. This may have implications for patient compliance and effectiveness of treatment in patients with chronic constipation.

21 CFR 189.175 - P-4000.

Code of Federal Regulations, 2011 CFR

2011-04-01

...-propoxyaniline, C9H12N2O3. It is a synthetic chemical having a sweet taste about 4000 times that of sucrose, is... for use as an artificial sweetener. (b) Food containing any added or detectable level of P-4000 is...

PEG-asparaginase induced severe hypertriglyceridemia.

PubMed

Galindo, Rodolfo J; Yoon, Justin; Devoe, Craig; Myers, Alyson K

2016-04-01

Asparaginase (ASP) is an effective chemotherapy agent extensively used in children with acute lymphocytic leukemia (ALL). There has been a recent interest in using ASP in adults with ALL, particularly the less toxic pegylated (PEG) formulation. Hypertriglyceridemia (HTG) is a rare complication of PEG-ASP therapy. We report two cases of obese patients who developed severe HTG after receiving PEG for ALL. Both patients were incidentally found to have severe HTG (TG of 4,330 and 4,420 mg/dL). In both patients, there was no personal or family history of dyslipidemia or hypothyroidism. There was no evidence of pancreatitis or skin manifestations of HTG. Both patients were treated with PEG cessation, low-fat diet and pharmacotherapy. Both patients were re-challenged with PEG, with subsequent increase in TG but no associated complications. TG returned to baseline after discontinuing PEG and while on therapy for HTG. A literature review of PEG-induced HTG in adults demonstrated similar results: asymptomatic presentation despite very severe HTG. HTG is a rare but clinically important adverse effect of PEG. Underlying obesity and/or diabetes may represent risk factors. Clinicians should monitor TG levels during PEG therapy to avoid TG-induced pancreatitis.

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

NASA Astrophysics Data System (ADS)

Wyszynski, Bartosz; Somboon, Pakpum; Nakamoto, Takamichi

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

12 CFR 614.4000 - Farm Credit Banks.

Code of Federal Regulations, 2010 CFR

2010-01-01

... institutions. (3) Farm Credit Banks, in their capacity as certified agricultural mortgage marketing facilities... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Farm Credit Banks. 614.4000 Section 614.4000 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM LOAN POLICIES AND OPERATIONS Lending...

24 CFR 4000.1 - Purpose and scope.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Purpose and scope. 4000.1 Section 4000.1 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) BOARD OF DIRECTORS OF THE HOPE FOR HOMEOWNERS PROGRAM BOARD OF DIRECTORS OF THE HOPE FOR HOMEOWNERS...

Improved enzymatic hydrolysis of microcrystalline cellulose (Avicel PH101) by polyethylene glycol addition.

PubMed

Ouyang, Jia; Dong, Zhenwei; Song, Xiangyang; Lee, Xin; Chen, Mu; Yong, Qiang

2010-09-01

The effects of additives on hydrolysis of microcrystalline cellulose (Avicel PH101) were examined using commercial cellulose-degrading enzymes (Celluclast 1.5L and Novozyme 188). Polyethylene glycol 4000 (PEG4000) was the most effective additive tested. When PEG4000 was added at 0.05 g/g glucan, the conversion of Avicel PH101 increased 91% (from 41.1% to 78.9%). The cellulase activity of Celluclast 1.5L increased 27.5% with PEG4000 addition. A positive effect on enzyme stabilities of Celluclast 1.5L and Novozyme 188 also occurred with PEG4000 addition. During hydrolysis process, significant changes in free protein concentration and cellulase activity were observed on Avicel PH101. More than 90% of the original enzyme activity remained in the solution after 48 h hydrolysis. Thus, PEG4000 addition is an efficient method to enhance digestibility of cellulosic materials and make enzyme recovery possible and valuable. This provides an opportunity of decreasing the operational cost of the hydrolysis process. (c) 2010 Elsevier Ltd. All rights reserved.

2 L PEG plus ascorbic acid versus 4 L PEG plus simethicon for colonoscopy preparation: a randomized single-blind clinical trial.

PubMed

Gentile, Maurizio; De Rosa, Michele; Cestaro, Giovanni; Forestieri, Pietro

2013-06-01

The 2 L polyethylene glycol (PEG) lavage solution has been proved to be similarly safe and effective as 4 L PEG formulations, in spite of the reduced volume. To compare low-volume PEG-based solution combined with ascorbic acid with high-volume PEG-based solution combined with simethicon in terms of efficacy and patient tolerability. This was a single-blind prospective randomized trial. Patients were randomized to receive either 2 L PEG plus ascorbic acid (PEG+Asc) or 4 L PEG plus simethicon (PEG+Sim). The primary endpoint was overall colon cleansing evaluation, assessed by blinded investigators using Aronchick score. Secondary end points included patient compliance and tolerability and adverse events. Sixty patients received PEG+Asc and 60 received PEG+Sim. Overall bowel cleansing score was considered adequate in 81.67% of the PEG+Asc and 80% of the PEG+Sim groups, respectively. Excellent and good ratings were recorded in 11.6% and 38.3% receiving PEG+Asc as compared with 26.6% and 23.3% of patients receiving PEG+Sim. Patient tolerability and safety were similar with both the preparations. According to our data, low-volume PEG+Asc has comparable efficacy, safety, and tolerability as high-volume PEG+Sim; therefore, it can be considered as a good alternative solution for bowel preparation. More improvements are necessary to achieve the target of a perfect preparation.

Highly efficient mesophyll protoplast isolation and PEG-mediated transient gene expression for rapid and large-scale gene characterization in cassava (Manihot esculenta Crantz).

PubMed

Wu, Jun-Zheng; Liu, Qin; Geng, Xiao-Shan; Li, Kai-Mian; Luo, Li-Juan; Liu, Jin-Ping

2017-03-14

Cassava (Manihot esculenta Crantz) is a major crop extensively cultivated in the tropics as both an important source of calories and a promising source for biofuel production. Although stable gene expression have been used for transgenic breeding and gene function study, a quick, easy and large-scale transformation platform has been in urgent need for gene functional characterization, especially after the cassava full genome was sequenced. Fully expanded leaves from in vitro plantlets of Manihot esculenta were used to optimize the concentrations of cellulase R-10 and macerozyme R-10 for obtaining protoplasts with the highest yield and viability. Then, the optimum conditions (PEG4000 concentration and transfection time) were determined for cassava protoplast transient gene expression. In addition, the reliability of the established protocol was confirmed for subcellular protein localization. In this work we optimized the main influencing factors and developed an efficient mesophyll protoplast isolation and PEG-mediated transient gene expression in cassava. The suitable enzyme digestion system was established with the combination of 1.6% cellulase R-10 and 0.8% macerozyme R-10 for 16 h of digestion in the dark at 25 °C, resulting in the high yield (4.4 × 10 7 protoplasts/g FW) and vitality (92.6%) of mesophyll protoplasts. The maximum transfection efficiency (70.8%) was obtained with the incubation of the protoplasts/vector DNA mixture with 25% PEG4000 for 10 min. We validated the applicability of the system for studying the subcellular localization of MeSTP7 (an H + /monosaccharide cotransporter) with our transient expression protocol and a heterologous Arabidopsis transient gene expression system. We optimized the main influencing factors and developed an efficient mesophyll protoplast isolation and transient gene expression in cassava, which will facilitate large-scale characterization of genes and pathways in cassava.

Modeling and self-assembly behavior of PEG-PLA-PEG triblock copolymers in aqueous solution

NASA Astrophysics Data System (ADS)

Wu, Xiaohan; Li, Suming; Coumes, Fanny; Darcos, Vincent; Lai Kee Him, Joséphine; Bron, Patrick

2013-09-01

A series of poly(ethylene glycol)-polylactide-poly(ethylene glycol) (PEG-PLA-PEG) triblock copolymers with symmetric or asymmetric chain structures were synthesized by combination of ring-opening polymerization and copper-catalyzed click chemistry. The resulting copolymers were used to prepare self-assembled aggregates by dialysis. Various architectures such as nanotubes, polymersomes and spherical micelles were observed from transmission electron microscopy (TEM), cryo-TEM and atomic force microscopy (AFM) measurements. The formation of diverse aggregates is explained by modeling from the angle of both geometry and thermodynamics. From the angle of geometry, a ``blob'' model based on the Daoud-Cotton model for star polymers is proposed to describe the aggregate structures and structural changes with copolymer composition and molar mass. In fact, the copolymer chains extend in aqueous medium to form single layer polymersomes to minimize the system's free energy if one of the two PEG blocks is short enough. The curvature of polymersomes is dependent on the chain structure of copolymers, especially on the length of PLA blocks. A constant branch number of aggregates (f) is thus required to preserve the morphology of polymersomes. Meanwhile, the aggregation number (Nagg) determined from the thermodynamics of self-assembly is roughly proportional to the total length of polymer chains. Comparing f to Nagg, the aggregates take the form of polymersomes if Nagg ~ f, and change to nanotubes if Nagg > f to conform to the limits from both curvature and aggregation number. The length of nanotubes is mainly determined by the difference between Nagg and f. However, the hollow structure becomes unstable when both PEG segments are too long, and the aggregates eventually collapse to yield spherical micelles. Therefore, this work gives new insights into the self-assembly behavior of PEG-PLA-PEG triblock copolymers in aqueous solution which present great interest for biomedical and

PEG tube insertion -- discharge

MedlinePlus

... be treated with medicine. Caring for the PEG-tube Site Drainage from around the PEG tube is common for the first 1 or 2 ... cotton swab or gauze. Try to remove any drainage or crusting on the skin and tube. Be gentle. If you used soap, gently clean ...

Same-day 2-L PEG-citrate-simethicone plus bisacodyl vs split 4-L PEG: Bowel cleansing for late-morning colonoscopy.

PubMed

de Leone, Annalisa; Tamayo, Darina; Fiori, Giancarla; Ravizza, Davide; Trovato, Cristina; De Roberto, Giuseppe; Fazzini, Linda; Dal Fante, Marco; Crosta, Cristiano

2013-09-16

To evaluate the efficacy, tolerability, acceptability and feasibility of bisacodyl plus low volume polyethyleneglycol-citrate-simeticone (2-L PEG-CS) taken the same day as compared with conventional split-dose 4-L PEG for late morning colonoscopy. Randomised, observer-blind, parallel group, comparative trial carried out in 2 centres. Out patients of both sexes, aged between 18 and 85 years, undergoing colonoscopy for diagnostic investigation, colorectal cancer screening or follow-up were eligible. The PEG-CS group received 3 bisacodyl tablets (4 tablets for patients with constipation) at bedtime and 2-L PEG-CS in the morning starting 5 h before colonoscopy. The control group received a conventional 4-L PEG formulation given as split regimen; the morning dose was taken with the same schedule of the low volume preparation. The Ottawa Bowel Preparation Scale (OBPS) score was used as the main outcome measure. A total of 164 subjects were enrolled and 154 completed the study; 78 in the PEG-CS group and 76 in the split 4-L PEG group. The two groups were comparable at baseline. The OBPS score in the PEG-CS group (3.09 ± 2.40) and in the PEG group (2.39 ± 2.55) were equivalent (difference +0.70; 95%CI: -0.09-1.48). This was confirmed by the rate of successful bowel cleansing in the PEG-CS group (89.7%) and in the PEG group (92.1%) (difference -2.4%; 95%CI: -11.40- 6.70). PEG-CS was superior in terms of mucosa visibility compared to PEG (85.7% vs 72.4%, P = 0.042). There were no significant differences in caecum intubation rate, time to reach the caecum and withdrawal time between the two groups. The adenoma detection rate was similar (PEG-CS 43.6% vs PEG 44.7%). No serious adverse events occurred. No difference was found in tolerability of the bowel preparations. Compliance was equal in both groups: more than 90% of subjects drunk the whole solution. Willingness to repeat the same bowel preparations was about 90% for both regimes. Same-day PEG-CS is feasible, effective

Characteristics and cytotoxicity of folate-modified curcumin-loaded PLA-PEG micellar nano systems with various PLA:PEG ratios.

PubMed

Phan, Quoc Thong; Le, Mai Huong; Le, Thi Thu Huong; Tran, Thi Hong Ha; Xuan, Phuc Nguyen; Ha, Phuong Thu

2016-06-30

Targeting delivery system use natural drugs for tumor cells is an appealing platform help to reduce the side effects and enhance the therapeutic effects of the drug. In this study, we synthesized curcumin (Cur) loaded (D, L Poly lactic - Poly ethylenglycol) micelle (Cur/PLA-PEG) with the ratio of PLA/PEG of 3:1 2:1 1:1 1:2 and 1:3 (w/w) and another micelle modified by folate (Cur/PLA-PEG-Fol) for targeting cancer therapy. The PLA-PEG copolymer was synthesized by ring opening polymerization method. After loading onto the micelle, solubility of Cur increased from 0.38 to 0.73mgml(-1). The average size of prepared Cur/PLA-PEG micelles was from 60 to 69nm (corresponding to the ratio difference of PLA/PEG) and the drug encapsulating efficiency was from 48.8 to 91.3%. Compared with the Cur/PLA-PEG micelles, the size of Cur/PLA-PEG-Fol micelles were from 80 to 86nm and showed better in vitro cellular uptake and cytotoxicity towards HepG2 cells. The cytotoxicity of the NPs however depends much on the PEG component. The results demonstrated that Folate-modified micelles could serve as a potential nano carrier to improve solubility, anti-cancer activity of Cur and targeting ability of the system. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of PEG and mPEG-co-(PGA-co-PDL) microparticles loaded with sodium diclofenac

PubMed Central

Tawfeek, Hesham M.

2013-01-01

The aim of this study was to synthesize and evaluate novel biodegradable polyesters namely; poly(ethylene glycol)-Poly(glycerol adipate-co-ω-pentadecalactone), PEG-PGA-co-PDL-PEG, and poly(ethylene glycol methyl ether)-Poly(glycerol adipate-co-ω-pentadecalactone), PGA-co-PDL-PEGme as an alternative sustained release carrier for lung delivery compared with non-PEG containing polymer PGA-co-PDL. The co-polymers were synthesized through lipase catalysis ring opening polymerization reaction and characterized using GPC, FT-IR, 1H-NMR and surface contact angle. Furthermore, microparticles containing a model hydrophilic drug, sodium diclofenac, were prepared via spray drying from a modified single emulsion and characterized for their encapsulation efficiency, geometrical particle size, zeta potential, tapped density, primary aerodynamic diameter, amorphous nature, morphology, in vitro release and the aerosolization performance. Microparticles fabricated from mPEG-co-polymer can be targeted to the lung periphery with an optimum in vitro deposition. Furthermore, a significantly higher in vitro release (p > 0.05, ANOVA/Dunnett’s) was observed with the PEG and mPEG-co-polymers compared to PGA-co-PDL. In addition, these co-polymers have a good safety profile upon testing on human bronchial epithelial, 16HBE14o- cell lines. PMID:24227959

Injector having multiple fuel pegs

DOEpatents

Hadley, Mark Allan; Felling, David Kenton

2013-04-30

A fuel injector is provided, including a fuel injector body, a plurality of fuel vanes, and a plurality of fuel pegs. The injector body includes a manifold and an inlet. The manifold is configured for receiving fuel, and the inlet is configured for receiving air. The fuel vanes are located within the injector body and are positioned in a direction that is generally parallel with a longitudinal axis of the injector body to orient the air flowing from the inlet. The plurality of fuel pegs are fluidly connected to the manifold and are arranged within the plurality of fuel vanes. The plurality of fuel pegs are each spaced at a distance that is about equal between each of the plurality of fuel pegs.

Same-day 2-L PEG-citrate-simethicone plus bisacodyl vs split 4-L PEG: Bowel cleansing for late-morning colonoscopy

PubMed Central

de Leone, Annalisa; Tamayo, Darina; Fiori, Giancarla; Ravizza, Davide; Trovato, Cristina; De Roberto, Giuseppe; Fazzini, Linda; Dal Fante, Marco; Crosta, Cristiano

2013-01-01

AIM: To evaluate the efficacy, tolerability, acceptability and feasibility of bisacodyl plus low volume polyethyleneglycol-citrate-simeticone (2-L PEG-CS) taken the same day as compared with conventional split-dose 4-L PEG for late morning colonoscopy. METHODS: Randomised, observer-blind, parallel group, comparative trial carried out in 2 centres. Out patients of both sexes, aged between 18 and 85 years, undergoing colonoscopy for diagnostic investigation, colorectal cancer screening or follow-up were eligible. The PEG-CS group received 3 bisacodyl tablets (4 tablets for patients with constipation) at bedtime and 2-L PEG-CS in the morning starting 5 h before colonoscopy. The control group received a conventional 4-L PEG formulation given as split regimen; the morning dose was taken with the same schedule of the low volume preparation. The Ottawa Bowel Preparation Scale (OBPS) score was used as the main outcome measure. RESULTS: A total of 164 subjects were enrolled and 154 completed the study; 78 in the PEG-CS group and 76 in the split 4-L PEG group. The two groups were comparable at baseline. The OBPS score in the PEG-CS group (3.09 ± 2.40) and in the PEG group (2.39 ± 2.55) were equivalent (difference +0.70; 95%CI: -0.09-1.48). This was confirmed by the rate of successful bowel cleansing in the PEG-CS group (89.7%) and in the PEG group (92.1%) (difference -2.4%; 95%CI: -11.40- 6.70). PEG-CS was superior in terms of mucosa visibility compared to PEG (85.7% vs 72.4%, P = 0.042). There were no significant differences in caecum intubation rate, time to reach the caecum and withdrawal time between the two groups. The adenoma detection rate was similar (PEG-CS 43.6% vs PEG 44.7%). No serious adverse events occurred. No difference was found in tolerability of the bowel preparations. Compliance was equal in both groups: more than 90% of subjects drunk the whole solution. Willingness to repeat the same bowel preparations was about 90% for both regimes. CONCLUSION: Same

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

PubMed

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

2016-05-01

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

Lubiprostone plus PEG electrolytes versus placebo plus PEG electrolytes for outpatient colonoscopy preparation: a randomized, double-blind placebo-controlled trial.

PubMed

Sofi, Aijaz A; Nawras, Ali T; Pai, Chetan; Samuels, Qiana; Silverman, Ann L

2015-01-01

Bowel preparation using large volume of polyethylene glycol (PEG) solutions is often poorly tolerated. Therefore, there are ongoing efforts to develop an alternative bowel cleansing regimen that should be equally effective and better tolerated. The aim of this study was to assess the efficacy of lubiprostone (versus placebo) plus PEG as a bowel cleansing preparation for colonoscopy. Our study was a randomized, double-blind placebo-controlled design. Patients scheduled for screening colonoscopy were randomized 1:1 to lubiprostone (group 1) or placebo (group 2) plus 1 gallon of PEG. The primary endpoints were patient's tolerability and endoscopist's evaluation of the preparation quality. The secondary endpoint was to determine any reduction in the amount of PEG consumed in the lubiprostone group compared with the placebo group. One hundred twenty-three patients completed the study and were included in the analysis. There was no difference in overall cleanliness. The volume of PEG was similar in both the groups. The volume of PEG approached significance as a predictor of improved score for both the groups (P = 0.054). Lubiprostone plus PEG was similar to placebo plus PEG in colon cleansing and volume of PEG consumed. The volume of PEG consumed showed a trend toward improving the quality of the colon cleansing.

29 CFR 4000.1 - What are these filing rules about?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 9 2010-07-01 2010-07-01 false What are these filing rules about? 4000.1 Section 4000.1 Labor Regulations Relating to Labor (Continued) PENSION BENEFIT GUARANTY CORPORATION GENERAL FILING, ISSUANCE, COMPUTATION OF TIME, AND RECORD RETENTION Filing Rules § 4000.1 What are these filing rules about...

MAPLE deposition of PLGA:PEG films for controlled drug delivery: Influence of PEG molecular weight

NASA Astrophysics Data System (ADS)

Paun, Irina Alexandra; Moldovan, Antoniu; Luculescu, Catalin Romeo; Staicu, Angela; Dinescu, Maria

2012-09-01

Implantable devices consisting of indomethacin (INC) cores coated with poly(lactide-co-glycolide):polyethylene glycol films (i.e. PLGA:PEG films) deposited by Matrix Assisted Pulsed Laser Evaporation (MAPLE) were produced. To predict their behavior after implantation inside the body, the implants were studied in vitro, in media similar with those encountered inside the body (phosphate buffered saline (PBS) pH 7.4 and blood). The influence of the molecular weight of PEG (i.e. low (1450 Da) versus high (10 kDa) molecular weights) on the characteristics of the implants was investigated, in terms of morphology, blood compatibility and kinetics of the drug release. The use of PEG of high molecular weight resulted in larger pores on the implants surfaces, enhanced blood compatibility of the implants and higher drug delivery rates. For both molecular weights PEGs, sustained release of INC was maintained over a three weeks interval. Theoretical fitting of the drug release data with Higuchi's model indicated that the INC was released mainly by diffusion, most probably through the pores formed in PLGA:PEG films during PBS immersion.

Solid freeform fabrication and in-vitro response of osteoblast cells of mPEG-PCL-mPEG bone scaffolds.

PubMed

Jiang, Cho-Pei; Chen, Yo-Yu; Hsieh, Ming-Fa; Lee, Hung-Maan

2013-04-01

Bone tissue engineering is an emerging approach to provide viable substitutes for bone regeneration. Poly(ethylene glycol) (PEG) is a good candidate of bone scaffold because of several advantages such as hydrophilicity, biocompatibility, and intrinsic resistance to protein adsorption and cell adhesion. However, its low compressive strength limits application for bone regeneration. Poly(ε-caprolactone) (PCL), a hydrophobic nonionic polymer, is adopted to enhance the compressive strength of PEG alone.We aimed to investigate the in-vitro response of osteoblast-like cells cultured with porous scaffolds of triblock PEG-PCL-PEG copolymer fabricated by an air pressure-aided deposition system. A desktop air pressure-aided deposition system that involves melting and plotting PEG-PCL-PEG was used to fabricate three-dimensional scaffolds having rectangular pores. The experimental results showed that PEG-PCL-PEG with a molecular weight of 25,000 can be melted and stably deposited through a heating nozzle at an air pressure of 0.3 MPa and no crack occurs after it solidifies. The scaffolds with pre-determined pore size of 400× 420 μm and a porosity of 79 % were fabricated, and their average compressive strength was found to be 18.2 MPa. Osteoblast-like cells, MC3T3-E1, were seeded on fabricated scaffolds to investigate the in-vitro response of cells including toxicity and cellular locomotion. In a culture period of 28 days, the neutral-red stained osteoblasts were found to well distributed in the interior of the scaffold. Furthermore, the cellular attachment and movement in the first 10 h of cell culture were observed with time-lapse microscopy indicating that the porous PEG-PCL-PEG scaffolds fabricated by air pressure-aided deposition system is non-toxicity for osteoblast-like cells.

Raman scattering studies on PEG functionalized hydroxyapatite nanoparticles

NASA Astrophysics Data System (ADS)

Yamini, D.; Devanand Venkatasubbu, G.; Kumar, J.; Ramakrishnan, V.

2014-01-01

The pure hydroxyapatite (HAP) nanoparticles (NPs) have been synthesized by wet chemical precipitation method. Raman spectral measurements have been made for pure HAP, pure Polyethylene glycol (PEG) 6000 and PEG coated HAP in different mass ratios (sample 1, sample 2 and sample 3). The peaks observed in Raman spectrum of pure HAP and the XRD pattern have confirmed the formation of HAP NPs. Vibrational modes have been assigned for pure HAP and pure PEG 6000. The observed variation in peak position of Raman active vibrational modes of PEG in PEG coated HAP has been elucidated in this work, in terms of intermolecular interactions between PEG and HAP. Further these results suggest that the functionalization of nanoparticles may be independent of PEG mass.

Pharmacokinetic analysis of multi PEG-theophylline conjugates.

PubMed

Grassi, Mario; Bonora, Gian Maria; Drioli, Sara; Cateni, Francesca; Zacchigna, Marina

2012-10-01

In the attempt of prolonging the effect of drugs, a new branched, high-molecular weight multimeric poly(ethylene glycol) (MultiPEG), synthesized with a simple assembling procedure that devised the introduction of functional groups with divergent and selective reactivity, was employed as drug carrier. In particular, the attention was focused on the study of theophylline (THEO) and THEO-MultiPEG conjugates pharmacokinetic after oral administration in rabbit. Pharmacokinetic behavior was studied according to an ad hoc developed mathematical model accounting for THEO-MultiPEG in vivo absorption and decomposition into drug (THEO) and carrier (MultiPEG). The branched high-molecular weight MultiPEG proved to be a reliable drug delivery system able to prolong theophylline staying in the blood after oral administration of a THEO-MultiPEG solution. The analysis of experimental data by means of the developed mathematical model revealed that the prolongation of THEO effect was essentially due to the low THEO-MultiPEG permeability in comparison to that of pure THEO. Copyright © 2012 Elsevier Ltd. All rights reserved.

Raman scattering studies on PEG functionalized hydroxyapatite nanoparticles.

PubMed

Yamini, D; Devanand Venkatasubbu, G; Kumar, J; Ramakrishnan, V

2014-01-03

The pure hydroxyapatite (HAP) nanoparticles (NPs) have been synthesized by wet chemical precipitation method. Raman spectral measurements have been made for pure HAP, pure Polyethylene glycol (PEG) 6000 and PEG coated HAP in different mass ratios (sample 1, sample 2 and sample 3). The peaks observed in Raman spectrum of pure HAP and the XRD pattern have confirmed the formation of HAP NPs. Vibrational modes have been assigned for pure HAP and pure PEG 6000. The observed variation in peak position of Raman active vibrational modes of PEG in PEG coated HAP has been elucidated in this work, in terms of intermolecular interactions between PEG and HAP. Further these results suggest that the functionalization of nanoparticles may be independent of PEG mass. Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical Interactions of Polyethylene Glycols (PEG) and Glycerol with Protein Functional Groups: Applications to PEG, Glycerol Effects on Protein Processes

PubMed Central

Knowles, DB; Shkel, Irina A; Phan, Noel M; Sternke, Matt; Lingeman, Emily; Cheng, Xian; Cheng, Lixue; O’Connor, Kevin; Record, M. Thomas

2015-01-01

Here we obtain the data needed to predict chemical interactions of polyethylene glycols (PEGs) and glycerol with proteins and related organic compounds, and thereby interpret or predict chemical effects of PEGs on protein processes. To accomplish this we determine interactions of glycerol and tetraEG with >30 model compounds displaying the major C, N, and O functional groups of proteins. Analysis of these data yields coefficients (α-values) quantifying interactions of glycerol, tetraEG and PEG end (-CH2OH) and interior (-CH2OCH2-) groups with these groups, relative to interactions with water. TetraEG (strongly) and glycerol (weakly) interact favorably with aromatic C, amide N, and cationic N, but unfavorably with amide O, carboxylate O and salt ions. Strongly unfavorable O and salt anion interactions help make both small and large PEGs effective protein precipitants. Interactions of tetraEG and PEG interior groups with aliphatic C are quite favorable, while interactions of glycerol and PEG end groups with aliphatic C are not. Hence tetraEG and PEG 300 favor unfolding of the DNA-binding domain of lac repressor (lacDBD) while glycerol, di- and mono-ethylene glycol are stabilizers. Favorable interactions with aromatic and aliphatic C explain why PEG400 greatly increases the solubility of aromatic hydrocarbons and steroids. PEG400-steroid interactions are unusually favorable, presumably because of simultaneous interactions of multiple PEG interior groups with the fused ring system of the steroid. Using α-values reported here, chemical contributions to PEG m-values can be predicted or interpreted in terms of changes in water-accessible surface area (ΔASA), and separated from excluded volume effects. PMID:25962980

Drop Printing of Pharmaceuticals: Effect of Molecular Weight on PEG Coated-Naproxen/PEG3350 Solid Dispersions

PubMed Central

Hsu, Hsin-Yun; Toth, Scott; Simpson, Garth J.; Harris, Michael T.

2016-01-01

Solid dispersions have been used to enhance the bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). However, the solid state phase, compositional uniformity, and scale-up problems are issues that need to be addressed. To allow for highly controllable products, the Drop Printing (DP) technique can provide precise dosages and predictable compositional uniformity of APIs in two/three dimensional structures. In this study, DP was used to prepare naproxen (NAP)/polyethylene glycol 3350 (PEG3350) solid dispersions with PEG coatings of different molecular weights (MW). A comparison of moisture-accelerated crystallization inhibition by different PEG coatings was assessed. Scanning electron microscopy (SEM), second harmonic generation (SHG) microscopy, and differential scanning calorimetry (DSC) analysis were performed to characterize the morphology and quantify the apparent crystallinity of NAP within the solid dispersions. Thermogravimetric analysis (TGA) was employed to measure the water content within each sample. The results suggest that the moisture-accelerated crystallization inhibition capability of the PEG coatings increased with increasing MW of the PEG coating. Besides, to demonstrate the flexibility of DP technology on manufacturing formulation, multilayer tablets with different PEG serving as barrier layers were also constructed, and their dissolution behavior was examined. By applying DP and appropriate materials, it is possible to design various carrier devices used to control the release dynamics of the API. PMID:27041744

Drop Printing of Pharmaceuticals: Effect of Molecular Weight on PEG Coated-Naproxen/PEG3350 Solid Dispersions.

PubMed

Hsu, Hsin-Yun; Toth, Scott; Simpson, Garth J; Harris, Michael T

2015-12-01

Solid dispersions have been used to enhance the bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). However, the solid state phase, compositional uniformity, and scale-up problems are issues that need to be addressed. To allow for highly controllable products, the Drop Printing (DP) technique can provide precise dosages and predictable compositional uniformity of APIs in two/three dimensional structures. In this study, DP was used to prepare naproxen (NAP)/polyethylene glycol 3350 (PEG3350) solid dispersions with PEG coatings of different molecular weights (MW). A comparison of moisture-accelerated crystallization inhibition by different PEG coatings was assessed. Scanning electron microscopy (SEM), second harmonic generation (SHG) microscopy, and differential scanning calorimetry (DSC) analysis were performed to characterize the morphology and quantify the apparent crystallinity of NAP within the solid dispersions. Thermogravimetric analysis (TGA) was employed to measure the water content within each sample. The results suggest that the moisture-accelerated crystallization inhibition capability of the PEG coatings increased with increasing MW of the PEG coating. Besides, to demonstrate the flexibility of DP technology on manufacturing formulation, multilayer tablets with different PEG serving as barrier layers were also constructed, and their dissolution behavior was examined. By applying DP and appropriate materials, it is possible to design various carrier devices used to control the release dynamics of the API.

Direct purification of pectinase from mango (Mangifera Indica Cv. Chokanan) peel using a PEG/salt-based Aqueous Two Phase System.

PubMed

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

2011-10-10

An Aqueous Two-Phase System (ATPS) was employed for the first time for the separation and purification of pectinase from mango (Mangifera Indica Cv. Chokanan) peel. The effects of different parameters such as molecular weight of the polymer (polyethylene glycol, 2,000-10,000), potassium phosphate composition (12-20%, w/w), system pH (6-9), and addition of different concentrations of neutral salts (0-8%, w/w) on partition behavior of pectinase were investigated. The partition coefficient of the enzyme was decreased by increasing the PEG molecular weight. Additionally, the phase composition showed a significant effect on purification factor and yield of the enzyme. Optimum conditions for purification of pectinase from mango peel were achieved in a 14% PEG 4000-14% potassium phosphate system using 3% (w/w) NaCl addition at pH 7.0. Based on this system, the purification factor of pectinase was increased to 13.2 with a high yield of (97.6%). Thus, this study proves that ATPS can be an inexpensive and effective method for partitioning of pectinase from mango peel.

Drag reduction by polyethylene glycol in the tail arterial bed of normotensive and hypertensive rats.

PubMed

Bessa, K L; Belletati, J F; Santos, L; Rossoni, L V; Ortiz, J P

2011-08-01

This study was designed to evaluate the effect of drag reducer polymers (DRP) on arteries from normotensive (Wistar) and spontaneously hypertensive rats (SHR). Polyethylene glycol (PEG 4000 at 5000 ppm) was perfused in the tail arterial bed with (E+) and without endothelium (E-) from male, adult Wistar (N = 14) and SHR (N = 13) animals under basal conditions (constant flow at 2.5 mL/min). In these preparations, flow-pressure curves (1.5 to 10 mL/min) were constructed before and 1 h after PEG 4000 perfusion. Afterwards, the tail arterial bed was fixed and the internal diameters of the arteries were then measured by microscopy and drag reduction was assessed based on the values of wall shear stress (WSS) by computational simulation. In Wistar and SHR groups, perfusion of PEG 4000 significantly reduced pulsatile pressure (Wistar/E+: 17.5 ± 2.8; SHR/E+: 16.3 ± 2.7%), WSS (Wistar/E+: 36; SHR/E+: 40%) and the flow-pressure response. The E- reduced the effects of PEG 4000 on arteries from both groups, suggesting that endothelial damage decreased the effect of PEG 4000 as a DRP. Moreover, the effects of PEG 4000 were more pronounced in the tail arterial bed from SHR compared to Wistar rats. In conclusion, these data demonstrated for the first time that PEG 4000 was more effective in reducing the pressure-flow response as well as WSS in the tail arterial bed of hypertensive than of normotensive rats and these effects were amplified by, but not dependent on, endothelial integrity. Thus, these results show an additional mechanism of action of this polymer besides its mechanical effect through the release and/or bioavailability of endothelial factors.

Informed peg-in-hole insertion using optical sensors

NASA Astrophysics Data System (ADS)

Paulos, Eric; Canny, John F.

1993-08-01

Peg-in-hole insertion is not only a longstanding problem in robotics but the most common automated mechanical assembly task. In this paper we present a high precision, self-calibrating peg-in-hole insertion strategy using several very simple, inexpensive, and accurate optical sensors. The self-calibrating feature allows us to achieve successful dead-reckoning insertions with tolerances of 25 microns without any accurate initial position information for the robot, pegs, or holes. The program we implemented works for any cylindrical peg, and the sensing steps do not depend on the peg diameter, which the program does not know. The key to the strategy is the use of a fixed sensor to localize both a mobile sensor and the peg, while the mobile sensor localizes the hole. Our strategy is extremely fast, localizing pegs as they are in route to their insertion location without pausing. The result is that insertion times are dominated by the transport time between pick and place operations.

Safety Evaluation of Polyethylene Glycol (PEG) Compounds for Cosmetic Use

PubMed Central

Shin, Chan Young; Kim, Kyu-Bong

2015-01-01

Polyethylene glycols (PEGs) are products of condensed ethylene oxide and water that can have various derivatives and functions. Since many PEG types are hydrophilic, they are favorably used as penetration enhancers, especially in topical dermatological preparations. PEGs, together with their typically nonionic derivatives, are broadly utilized in cosmetic products as surfactants, emulsifiers, cleansing agents, humectants, and skin conditioners. The compounds studied in this review include PEG/PPG-17/6 copolymer, PEG-20 glyceryl triisostearate, PEG-40 hydrogenated castor oil, and PEG-60 hydrogenated castor oil. Overall, much of the data available in this review are on PEGylated oils (PEG-40 and PEG-60 hydrogenated castor oils), which were recommended as safe for use in cosmetics up to 100% concentration. Currently, PEG-20 glyceryl triisostearate and PEGylated oils are considered safe for cosmetic use according to the results of relevant studies. Additionally, PEG/PPG-17/6 copolymer should be further studied to ensure its safety as a cosmetic ingredient. PMID:26191379

High density load bearing insulation peg

DOEpatents

Nowobilski, Jeffert J.; Owens, William J.

1985-01-01

A high density peg which can support a large load and exhibits excellent thermal resistance produced by a method wherein the peg is made in compliance with specified conditions of time, temperature and pressure.

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

NASA Astrophysics Data System (ADS)

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

2010-04-01

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

High density load bearing insulation peg

DOEpatents

Nowobilski, J.J.; Owens, W.J.

1985-01-29

A high density peg is disclosed which can support a large load and exhibits excellent thermal resistance produced by a method wherein the peg is made in compliance with specified conditions of time, temperature and pressure. 4 figs.

An Experimental Investigation of Potential Icing of the Space Shuttle External Tank,

DTIC Science & Technology

1982-09-01

PEG 4000, a PEG 1000/400 mixture, and PEG 6000. The number corresponds to the molecular weight of the compound. 2 4.65m Foam Inslation Side 8 ob o 4m(l...Level Emiseivity panel (PEG coated) (Uncoated) Emissivity Panel Left Right 1 4.4 -28.8 -31.6 4.7 -12.2 -15.3 2 4.4 -20.2 -22.2 4.7 -12.8 -13.4 3 4.3...constant dry bulb temperature of 60*F. PEG was tested on one half of side A of the panel. A mixture of 450 g of molecular weight 4000 PEG and 400 g of H20

Temperature-responsive in situ nanoparticle hydrogels based on hydrophilic pendant cyclic ether modified PEG-PCL-PEG.

PubMed

Feng, Zujian; Zhao, Junqiang; Li, Yin; Xu, Shuxin; Zhou, Junhui; Zhang, Jianhua; Deng, Liandong; Dong, Anjie

2016-10-20

Thermo-sensitive injectable hydrogels based on poly(ε-caprolactone)/poly(ethylene glycol) (PCL/PEG) block copolymers have attracted considerable attention for sustained drug release and tissue engineering applications. Previously, we have reported a thermo-sensitive hydrogel of P(CL-co-TOSUO)-PEG-P(CL-co-TOSUO) (PECT) triblock copolymers modified by hydrophilic cyclic ether pendant groups 1,4,8-trioxa-[4.6]spiro-9-undecanone (TOSUO). Unfortunately, the low gel modulus of PECT (only 50-70 Pa) may limit its applications. Herein, another kind of thermogelling triblock copolymer of a pendant cyclic ether-modified caprolactonic poloxamer analog, PEG-P(CL-co-TOSUO)-PEG (PECTE), was successfully prepared by control of the hydrophilicity/hydrophobicity balance and chemical compositions of the copolymers. PECTE powder could directly disperse in water to form a stable nanoparticle (NP) aqueous dispersion and underwent sol-gel-sol transition behavior at a higher concentration with the temperature increasing from ambient or lower temperatures. Significantly, the microstructure parameters (e.g., different chemical compositions of the hydrophobic block and topology) played a critical role in the phase transition behavior. Furthermore, comparison studies on PECTE and PEG-PCL-PEG (PECE) showed that the introduction of pendant cyclic ether groups into PCL blocks could avoid unexpected ahead-of-time gelling of the PECE aqueous solution. In addition, the rheological analysis of PECTE and PECT indicated that the storage modulus of the PECTE hydrogel could be 100 times greater than that of the PECT hydrogel under the same mole ratios of TOSUO/CL and lower molecular weight. Consequently, PECTE thermal hydrogel systems are believed to be promising as in situ gel-forming biomaterials for drug delivery and tissue engineering.

Efficacy and tolerability of peg-only laxative on faecal impaction and chronic constipation in children. A controlled double blind randomized study vs a standard peg-electrolyte laxative

PubMed Central

2012-01-01

Background PEG-based laxatives are considered today the gold standard for the treatment of constipation in children. PEG formulations differ in terms of composition of inactive ingredients which may have an impact on acceptance, compliance and adherence to treatment. We therefore compared the efficacy, tolerability, acceptance and compliance of a new PEG-only formulation compared to a reference PEG-electrolyte (PEG-EL) formulation in resolving faecal impaction and in the treatment of chronic constipation. Methods Children aged 2–16 years with functional chronic constipation for at least 2 months were randomized to receive PEG-only 0.7 g/kg/day in 2 divided doses or 6.9 g PEG-EL 1–4 sachets according to age for 4 weeks. Children with faecal impaction were randomized to receive PEG-only 1.5/g/kg in 2 divided doses until resolution or for 6 days or PEG-EL with an initial dose of 4 sachets and increasing 2 sachets a day until resolution or for 7 days. Results Ninety-six children were randomized into the study. Five patients withdrew consent before starting treatment. Three children discontinued treatment for refusal due to bad taste of the product (1 PEG-only, 2 PEG-EL); 1 (PEG-EL) for an adverse effect (abdominal pain). Intent-to-treat analysis was carried out in 49 children in the PEG-only group and 42 in the PEG-EL group. No significant differences were observed between the two treatment groups at baseline. Adequate relief of constipation in terms of normalized frequency and painless defecation of soft stools was achieved in all patients in both groups. The number of stools/week was 9.2 ± 3.2 (mean ± SD) in the PEG-only group and 7.8 ± 2.4 in the PEG-EL group (p = 0.025); the number of days with stool was 22.4 ± 5.1 in the PEG-only group and 19.6 ± 7.2 in the PEG-EL group (p = 0.034). In the PEG-only group faecaloma resolution was observed in 5 children on the second day and in 2 children on the third day, while in the PEG-EL group it was observed in 2

30 CFR 56.4000 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... sufficient vapor is released by a liquid to form a flammable vapor-air mixture near the surface of the liquid... Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Fire Prevention and Control § 56.4000...

30 CFR 56.4000 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... sufficient vapor is released by a liquid to form a flammable vapor-air mixture near the surface of the liquid... Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Fire Prevention and Control § 56.4000...

30 CFR 56.4000 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... sufficient vapor is released by a liquid to form a flammable vapor-air mixture near the surface of the liquid... Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Fire Prevention and Control § 56.4000...

30 CFR 56.4000 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... sufficient vapor is released by a liquid to form a flammable vapor-air mixture near the surface of the liquid... Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Fire Prevention and Control § 56.4000...

Additives enhancing enzymatic hydrolysis of lignocellulosic biomass.

PubMed

Rocha-Martín, Javier; Martinez-Bernal, Claudio; Pérez-Cobas, Yolanda; Reyes-Sosa, Francisco Manuel; García, Bruno Díez

2017-11-01

Linked to the development of cellulolytic enzyme cocktails from Myceliophthora thermophila, we studied the effect of different additives on the enzymatic hydrolysis yield. The hydrolysis of pretreated corn stover (PCS), sugar cane straw (PSCS) and microcrystalline cellulose (Avicel) was performed under industrial conditions using high solid loadings, limited mixing, and low enzyme dosages. The addition of polyethylene glycol (PEG4000) allowed to increase the glucose yields by 10%, 7.5%, and 32%, respectively in the three materials. PEG4000 did not have significant effect on the stability of the main individual enzymes but increased beta-glucosidase and endoglucanase activity by 20% and 60% respectively. Moreover, the presence of PEG4000 accelerated cellulase-catalyzed hydrolysis reducing up to 25% the liquefaction time. However, a preliminary economical assessment concludes that even with these improvements, a lower contribution of PEG4000 to the 2G bioethanol production costs would be needed to reach commercial feasibility. Copyright © 2017. Published by Elsevier Ltd.

Residual Stresses in SAVY 4000 and Hagan Container Bodies

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

Stroud, Mary Ann; Hill, Mary Ann; Tokash, Justin Charles

Chloride-induced stress corrosion cracking (SCC) has been investigated as a potential failure mechanism for the SAVY 4000 and the Hagan containers used to store plutonium-bearing materials at Los Alamos National Laboratory. This report discusses the regions of the container bodies most susceptible to SCC and the magnitude of the residual stresses in those regions. Boiling MgCl2 testing indicated that for both containers the region near the top weld was most susceptible to SCC. The Hagan showed through wall cracking after 22-24 hours of exposure both parallel (axial stresses) and perpendicular (hoop stresses) to the weld. The SAVY 4000 container showedmore » significant cracking above and below the weld after 47 hours of exposure but there was no visual evidence of a through wall crack and the cracks did not leak water. Two through wall holes formed in the bottom of the SAVY 4000 container after 44-46 hours of exposure. For both containers, average “through wall” residual stresses were determined from hole drilling data 4 mm below the weld. In the Hagan body, average tensile hoop stresses were 194 MPa and average compressive axial stresses were -120 MPa. In the SAVY 4000 body, average compressive hoop stresses were 11 MPa and average tensile axial stresses were 25 MPa. Results suggest that because the Hagan container exhibited through wall cracking in a shorter time in boiling MgCl2 and had the higher average tensile stress, 194 MPa hoop stress, it is more susceptible to SCC than the SAVY 4000 container.« less

Role of the Methoxy Group in Immune Responses to mPEG-Protein Conjugates

PubMed Central

2012-01-01

Anti-PEG antibodies have been reported to mediate the accelerated clearance of PEG-conjugated proteins and liposomes, all of which contain methoxyPEG (mPEG). The goal of this research was to assess the role of the methoxy group in the immune responses to mPEG conjugates and the potential advantages of replacing mPEG with hydroxyPEG (HO-PEG). Rabbits were immunized with mPEG, HO-PEG, or t-butoxyPEG (t-BuO-PEG) conjugates of human serum albumin, human interferon-α, or porcine uricase as adjuvant emulsions. Assay plates for enzyme-linked immunosorbent assays (ELISAs) were coated with mPEG, HO-PEG, or t-BuO-PEG conjugates of the non-cross-reacting protein, porcine superoxide dismutase (SOD). In sera from rabbits immunized with HO-PEG conjugates of interferon-α or uricase, the ratio of titers of anti-PEG antibodies detected on mPEG-SOD over HO-PEG-SOD (“relative titer”) had a median of 1.1 (range 0.9–1.5). In contrast, sera from rabbits immunized with mPEG conjugates of three proteins had relative titers with a median of 3.0 (range 1.1–20). Analyses of sera from rabbits immunized with t-BuO-PEG-albumin showed that t-butoxy groups are more immunogenic than methoxy groups. Adding Tween 20 or Tween 80 to buffers used to wash the assay plates, as is often done in ELISAs, greatly reduced the sensitivity of detection of anti-PEG antibodies. Competitive ELISAs revealed that the affinities of antibodies raised against mPEG-uricase were c. 70 times higher for 10 kDa mPEG than for 10 kDa PEG diol and that anti-PEG antibodies raised against mPEG conjugates of three proteins had >1000 times higher affinities for albumin conjugates with c. 20 mPEGs than for analogous HO-PEG-albumin conjugates. Overall, these results are consistent with the hypothesis that antibodies with high affinity for methoxy groups contribute to the loss of efficacy of mPEG conjugates, especially if multiply-PEGylated. Using monofunctionally activated HO-PEG instead of mPEG in preparing conjugates for

30 CFR 57.4000 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

....4000 Definitions. The following definitions apply in this subpart. Combustible liquids. Liquids having... liquids—those having flash points at or above 100 °F (37.8 °C) and below 140 °F (60 °C). Class IIIA liquids—those having flash points at or above 140 °F (60 °C) and below 200 °F (93.4 °C). Class IIIB...

30 CFR 57.4000 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

....4000 Definitions. The following definitions apply in this subpart. Combustible liquids. Liquids having... liquids—those having flash points at or above 100 °F (37.8 °C) and below 140 °F (60 °C). Class IIIA liquids—those having flash points at or above 140 °F (60 °C) and below 200 °F (93.4 °C). Class IIIB...

Eutectic, monotectic and immiscibility systems of nimesulide with water-soluble carriers: phase equilibria, solid-state characterisation and in-vivo/pharmacodynamic evaluation.

PubMed

Abdelkader, Hamdy; Abdallah, Ossama Y; Salem, Hesham; Alani, Adam W G; Alany, Raid G

2014-10-01

The solid-state interactions of fused mixtures nimesulide (ND) with polyethylene glycol (PEG) 4000, urea or mannitol were studied through constructing thaw-melt phase equilibrium diagrams. The solid-state characteristics were investigated using differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Various types of interactions were identified such as the formation of a eutectic system of ND-PEG 4000, monotectic system of ND-urea and complete solid immiscibility of ND with mannitol. The effects of carrier concentrations on the equilibrium solubility and in-vitro dissolution characteristics were studied. Linear increases (R(2)  > 0.99) in the aqueous solubility of ND in various concentrations of PEG 4000 and urea were obtained, whereas mannitol did not exhibit any effect on the solubility of ND. Similar trends were obtained with the dissolution efficiency of the fused mixtures of ND with PEG 4000 and urea compared with the corresponding physical mixtures and untreated drug. The analgesic effects of untreated ND and the selected formulations were investigated by evaluating the drug's ability to inhibit the acetic acid-induced writhing response. The analgesic effect of ND in a eutectic mixture with PEG 4000 and a monotectic mixture with urea was potentiated by 3.2 and 2.7-fold respectively compared with the untreated drug. © 2014 Royal Pharmaceutical Society.

Decorin causes autophagy in endothelial cells via Peg3

PubMed Central

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

2013-01-01

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

PEG-protein interaction induced contraction of NalD chains.

PubMed

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

2014-01-01

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

Dissolution and oral bioavailability enhancement of praziquantel by solid dispersions.

PubMed

Liu, Yanyan; Wang, Tianzi; Ding, Wenya; Dong, Chunliu; Wang, Xiaoting; Chen, Jianqing; Li, Yanhua

2018-06-01

The aim of the present investigation was to enhance the solubility, dissolution, and oral bioavailability of praziquantel (PZQ), a poorly water-soluble BCS II drug (Biopharmaceutical Classification System), using a solid dispersion (SD) technique involving hydrophilic copolymers. The SD formulations were prepared by a solvent evaporation method with PZQ and PEG 4000 (polyethylene glycol 4000), PEG 6000, or P 188 polymers at various weight ratios or a combination of PEG 4000/P 188. The optimized SD formulation, which had the highest solubility in distilled water, was further characterized by its surface morphology, crystallinity, and dissolution in 0.1 M HCl with 0.2% w/v of sodium dodecyl sulfate (SDS). X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) revealed the amorphous form of PZQ in the SDs. Moreover, at an oral dosage of 5 mg/kg PZQ, the SDs had higher C max values and areas under the curve (AUCs) compared to those of commercial PZQ tablets. Preparation of PZQ-loaded SDs using PEG 4000/P 188 is a promising strategy to improve the oral bioavailability of PZQ.

21 CFR 189.175 - P-4000.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true P-4000. 189.175 Section 189.175 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES PROHIBITED FROM USE IN HUMAN FOOD Substances Generally Prohibited From...

21 CFR 189.175 - P-4000.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false P-4000. 189.175 Section 189.175 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES PROHIBITED FROM USE IN HUMAN FOOD Substances Generally Prohibited From...

21 CFR 189.175 - P-4000.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false P-4000. 189.175 Section 189.175 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES PROHIBITED FROM USE IN HUMAN FOOD Substances Generally Prohibited From...

Allergic reaction to polyethylene glycol in a painter.

PubMed

Antolin-Amerigo, D; Sánchez-González, M J; Barbarroja-Escudero, J; Rodríguez-Rodríguez, M; Álvarez-Perea, A; Alvarez-Mon, M

2015-08-01

We report a case of a male painter who visited our outpatient clinic after developing a distinct skin reaction 15 min after the ingestion of a laxative solution containing polyethylene glycol (PEG) prior to colonoscopy. He described suffering from the same skin reaction when he was previously exposed to paints that contained PEG-4000. An exposure challenge test with pure PEG-4000, simulating his workplace conditions, elicited a generalized urticarial reaction. Allergy to PEG should be considered in painters who develop urticarial or other systemic symptoms after handling PEG-containing products. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PEG-based degradable networks for drug delivery applications

NASA Astrophysics Data System (ADS)

Ostroha, Jamie L.

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

PEG attachment to osteoblasts enhances mechanosensitivity.

PubMed

Hamamura, Kazunori; Weng, Yiming; Zhao, Jun; Yokota, Hiroki; Xie, Dong

2008-06-01

Fluid flow induces proliferation and differentiation of osteoblasts, and fibrous structure like a primary cilium on a cell surface contributes to flow sensing and flow-driven gene regulation. We address a question: Does attachment of synthetic polymers on a cell surface enhance mechanosensitivity of osteoblasts? Using MC3T3 osteoblast cells (C4 clone) and a PEG polymer, one of whose termini was covalently linked to a succinimidyl succinate group (functionalized PEG-PEGSS), we examined attachment of PEGSS to osteoblasts and evaluated its effects on the mRNA expression of stress-responsive genes. AFM images exhibited globular PEGSS conformation of approximately 100 nm in size, and SEM images confirmed the attachment of a cluster of pancake-like PEGSS molecules on the osteoblast surface. Compared to control cells incubated with unfunctionalized PEG, real-time PCR revealed that RNA upregulation of c-fos, egr1, ATF3 and Cox2 genes was magnified in the cells incubated with PEGSS. These results support a PEG-induced increase in mechanosensitivity of osteoblasts and indicate that the described approach would be useful to accelerate growth and development of osteoblasts for bone repair and tissue engineering.

PEG-Protein Interaction Induced Contraction of NalD Chains

PubMed Central

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

2014-01-01

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

Protein resistance of dextran and dextran-PEG copolymer films

PubMed Central

Kozak, Darby; Chen, Annie; Bax, Jacinda; Trau, Matt

2011-01-01

The protein resistance of dextran and dextran-poly(ethylene glycol) (PEG) copolymer films was examined on an organosilica particle-based assay support. Comb-branched dextran-PEG copolymer films were synthesized in a two step process using the organosilica particle as a solid synthetic support. Particles modified with increasing amounts (0.1-1.2 mg m−2) of three molecular weights (10 000, 66 900, 400 000 g mol−1) of dextran were found to form relatively poor protein-resistant films compared to dextran-PEG copolymers and previously studied PEG films. The efficacy of the antifouling polymer films was found to be dependent on the grafted amount and its composition, with PEG layers being the most efficient, followed by dextran-PEG copolymers, and dextran alone being the least efficient. Immunoglobulin gamma (IgG) adsorption decreased from ~ 5 to 0.5 mg m−2 with increasing amounts of grafted dextran, but bovine serum albumin (BSA) adsorption increased above monolayer coverage (to ~2 mg m−2) indicating ternary adsorption of the smaller protein within the dextran layer. PMID:21614699

A method to optimize PEG-coating of red blood cells.

PubMed

Hashemi-Najafabadi, Sameereh; Vasheghani-Farahani, Ebrahim; Shojaosadati, Seyed Abbas; Rasaee, Mohammad Javad; Armstrong, Jonathan K; Moin, Mostafa; Pourpak, Zahra

2006-01-01

Alloimmunization to donor blood group antigens remains a significant problem in transfusion medicine. A proposed method to overcome donor-recipient blood group incompatibility is to mask the blood group antigens by the covalent attachment of poly(ethylene glycol) (PEG) to the red blood cell (RBC) membrane. Despite much work in the development of PEG-coating of RBCs, there is a paucity of data on the optimization of the PEG-coating technique; it is the aim of this study to determine the optimum conditions for PEG coating using a cyanuric chloride reactive derivative of methoxy-PEG as a model polymer. Activated PEG of molecular mass 5 kDa was covalently attached to human RBCs under various reaction conditions. Inhibition of binding of a blood-type specific antiserum (anti-D) was employed to evaluate the effect of the PEG-coating, quantified by hemocytometry and flow-cytometry. RBC morphology was examined by light and scanning electron microscopy. Statistical analysis of experimental design together with microscopy results showed that the optimum PEGylation conditions are pH = 8.7, temperature = 14 degrees C, and reaction time = 30 min. An optimum concentration of reactive PEG could not be determined. At high polymer concentrations (>25 mg/mL) a predominance of type III echinocytes was observed, and as a result, a concentration of 15 mg/mL is the highest recommended concentration for a linear PEG of molecular mass 5 kDa.

Quantitative analysis of PEG-functionalized colloidal gold nanoparticles using charged aerosol detection.

PubMed

Smith, Mackensie C; Crist, Rachael M; Clogston, Jeffrey D; McNeil, Scott E

2015-05-01

Surface characteristics of a nanoparticle, such as functionalization with polyethylene glycol (PEG), are critical to understand and achieve optimal biocompatibility. Routine physicochemical characterization such as UV-vis spectroscopy (for gold nanoparticles), dynamic light scattering, and zeta potential are commonly used to assess the presence of PEG. However, these techniques are merely qualitative and are not sensitive enough to distinguish differences in PEG quantity, density, or presentation. As an alternative, two methods are described here which allow for quantitative measurement of PEG on PEGylated gold nanoparticles. The first, a displacement method, utilizes dithiothreitol to displace PEG from the gold surface. The dithiothreitol-coated gold nanoparticles are separated from the mixture via centrifugation, and the excess dithiothreitol and dissociated PEG are separated through reversed-phase high-performance liquid chromatography (RP-HPLC). The second, a dissolution method, utilizes potassium cyanide to dissolve the gold nanoparticles and liberate PEG. Excess CN(-), Au(CN)2 (-), and free PEG are separated using RP-HPLC. In both techniques, the free PEG can be quantified against a standard curve using charged aerosol detection. The displacement and dissolution methods are validated here using 2-, 5-, 10-, and 20-kDa PEGylated 30-nm colloidal gold nanoparticles. Further value in these techniques is demonstrated not only by quantitating the total PEG fraction but also by being able to be adapted to quantitate the free unbound PEG and the bound PEG fractions. This is an important distinction, as differences in the bound and unbound PEG fractions can affect biocompatibility, which would not be detected in techniques that only quantitate the total PEG fraction.

21 CFR 189.175 - P-4000.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false P-4000. 189.175 Section 189.175 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES PROHIBITED FROM USE IN HUMAN FOOD Substances Generally Prohibited From Direct Addition or Use as Human Food § 189...

Preparation of PEG-conjugated fullerene containing Gd3+ ions for photodynamic therapy.

PubMed

Liu, Jian; Ohta, Shin-Ichi; Sonoda, Akinaga; Yamada, Masatoshi; Yamamoto, Masaya; Nitta, Norihisa; Murata, Kiyoshi; Tabata, Yasuhiko

2007-01-22

A novel photosensitizer with magnetic resonance imaging (MRI) activity was designed from fullerene (C(60)) for efficient photodynamic therapy (PDT) of tumor. After chemical conjugation of polyethylene glycol (PEG) to C(60) (C(60)-PEG), diethylenetriaminepentaacetic acid (DTPA) was subsequently introduced to the terminal group of PEG to prepare PEG-conjugated C(60) (C(60)-PEG-DTPA). The C(60)-PEG-DTPA was mixed with gadolinium acetate solution to obtain Gd(3+)-chelated C(60)-PEG (C(60)-PEG-Gd). Following intravenous injection of C(60)-PEG-Gd into tumor-bearing mice, the PDT anti-tumor effect and the MRI tumor imaging were evaluated. The similar O(2)(*-)generation was observed with or without Gd(3+) chelation upon light irradiation. Both of the C(60)-PEG-Gd and Magnevist(R) aqueous solutions exhibited a similar MRI activity. When intravenously injected into tumor-bearing mice, the C(60)-PEG-Gd maintained an enhanced MRI signal at the tumor tissue for a longer time period than Magnevist(R). Injection of C(60)-PEG-Gd plus light irradiation showed significant tumor PDT effect although the effect depended on the timing of light irradiation. The PDT efficacy of C(60)-PEG-Gd was observed at the time when the tumor accumulation was detected by the enhanced intensity of MRI signal. This therapeutic and diagnostic hybrid system is a promising tool to enhance the PDT efficacy for tumor.

Elasticity of bilayers containing PEG lipids

NASA Astrophysics Data System (ADS)

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

1998-02-01

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

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

PubMed

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

2001-01-01

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

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

PubMed

2006-01-01

Triethylene Glycol and PEG-4 (polyethylene glycol) are polymers of ethylene oxide alcohol. Triethylene Glycol is a specific three-unit chain, whereas PEG-4 is a polymer with an average of four units, but may contain polymers ranging from two to eight ethylene oxide units. In the same manner, other PEG compounds, e.g., PEG-6, are mixtures and likely contain some Triethylene Glycol and PEG-4. Triethylene Glycol is a fragrance ingredient and viscosity decreasing agent in cosmetic formulations, with a maximum concentration of use of 0.08% in skin-cleansing products. Following oral doses, Triethylene Glycol and its metabolites are excreted primarily in urine, with small amounts released in feces and expired air. With oral LD50 values in rodents from 15 to 22 g/kg, this compound has little acute toxicity. Rats given short term oral doses of 3% in water showed no signs of toxicity, whereas all rats given 10% died by the 12th day of exposure. At levels up to 1 g/m3, rats exposed to aerosolized Triethylene Glycol for 6 h per day for 9 days showed no signs of toxicity. Rats fed a diet containing 4% Triethylene Glycol for 2 years showed no signs of toxicity. There were no treatment-related effects on rats exposed to supersaturated Triethylene Glycol vapor for 13 months nor in rats that consumed 0.533 cc Triethylene Glycol per day in drinking water for 13 months. Triethylene Glycol was not irritating to the skin of rabbits and produced only minimal injury to the eye. In reproductive and developmental toxicity studies in rats and mice, Triethylene Glycol did not produce biologically significant embryotoxicity or teratogenicity. However, some maternal toxicity was seen in dams given 10 ml/kg/day during gestation. Triethylene Glycol was not mutagenic or genotoxic in Ames-type assays, the Chinese hamster ovary mutation assay, and the sister chromatid exchange assays. PEG-4 is a humectant and solvent in cosmetic products, with a maximum concentration of use of 20% in the "other

Assessment of the Intestinal Barrier with Five Different Permeability Tests in Healthy C57BL/6J and BALB/cJ Mice.

PubMed

Volynets, Valentina; Reichold, Astrid; Bárdos, Gyöngyi; Rings, Andreas; Bleich, André; Bischoff, Stephan C

2016-03-01

Intestinal permeability is thought to be of major relevance for digestive and nutrition-related diseases, and therefore has been studied in numerous mouse models of disease. However, it is unclear which tools are the preferable ones, and how normal values should be defined. To compare different in vivo permeability tests in healthy mice of commonly used genetic backgrounds. We assessed the intestinal barrier in male and female C57BL/6J and BALB/cJ mice of different ages, using four orally administered permeability markers, FITC-dextran 4000 (FITC-D4000) and ovalbumin (OVA) measured in plasma, and polyethylene glycol (PEG) and lactulose/mannitol (Lac/Man) measured in urine, and by assessing lipopolysaccharide (LPS) in portal vein plasma. After gavage, FITC-D4000, OVA, Lac/Man, and PEG400, but not PEG4000, were detectable in plasma or urine. Female mice tended to have a higher permeability according to the FITC-D4000, OVA, and PEG400 tests, but the Lac/Man ratio was higher in males. No significant differences between the two mouse strains of young and old mice were observed except for mannitol recovery, which was higher in BALB/cJ mice compared to C57BL/6J mice (p < 0.05). Virtually no LPS was detected in healthy mice. For all markers, normal values have been defined based on 5th-95th percentile ranges of our data. Selected oral permeability tests, such as FITC-D4000, OVA, PEG400, and Lac/Man, as well as LPS measurements in portal vein plasma, could be suitable for the evaluation of the intestinal barrier in mice, if used in a standardized way.

29 CFR 4000.28 - What if I send a computer disk?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 9 2014-07-01 2014-07-01 false What if I send a computer disk? 4000.28 Section 4000.28... I send a computer disk? (a) In general. We determine your filing or issuance date for a computer... paragraph (b) of this section. (1) Filings. For computer-disk filings, we may treat your submission as...

29 CFR 4000.28 - What if I send a computer disk?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 9 2013-07-01 2013-07-01 false What if I send a computer disk? 4000.28 Section 4000.28... I send a computer disk? (a) In general. We determine your filing or issuance date for a computer... paragraph (b) of this section. (1) Filings. For computer-disk filings, we may treat your submission as...

29 CFR 4000.28 - What if I send a computer disk?

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 9 2012-07-01 2012-07-01 false What if I send a computer disk? 4000.28 Section 4000.28... I send a computer disk? (a) In general. We determine your filing or issuance date for a computer... paragraph (b) of this section. (1) Filings. For computer-disk filings, we may treat your submission as...

29 CFR 4000.28 - What if I send a computer disk?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 9 2010-07-01 2010-07-01 false What if I send a computer disk? 4000.28 Section 4000.28... I send a computer disk? (a) In general. We determine your filing or issuance date for a computer... paragraph (b) of this section. (1) Filings. For computer-disk filings, we may treat your submission as...

29 CFR 4000.28 - What if I send a computer disk?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 9 2011-07-01 2011-07-01 false What if I send a computer disk? 4000.28 Section 4000.28... I send a computer disk? (a) In general. We determine your filing or issuance date for a computer... paragraph (b) of this section. (1) Filings. For computer-disk filings, we may treat your submission as...

The Effect of Created Local Hyperosmotic Microenvironment in Microcapsule for the Growth and Metabolism of Osmotolerant Yeast Candida krusei

PubMed Central

Chen, Guo; Yao, Shanjing

2013-01-01

Candida krusei is osmotolerant yeast used for the production of glycerol. Addition of osmolyte such as NaCl into culture medium can increase the production of glycerol from glucose, but osmolytes may burden the glycerol separation. A coencapsulation method was suggested to create local extracellular hyperosmotic stress for glycerol accumulation. Firstly, the influence of osmotic stress induced by the addition of PEG4000 on growth and metabolism of free cell was studied in detail. Glycerol accumulation could be improved by employing PEG4000 as osmoregulator. Secondly, cells and PEG4000 were coentrapped in NaCS/PDMDAAC capsules to create local hyperosmotic stress. The effects of local hyperosmotic microenvironment on the cell growth and metabolism were studied. The coentrapment method increased the glycerol concentration by 25%, and the glycerol concentration attained 50 gL−1 with productivity of 18.8 gL−1Day−1 in shake flask. More importantly, the glycerol could be directly separated from the encapsulated cells. The entrapped cells containing PEG4000 were also cultivated for 15 days in an airlift reactor. The yield and productivity were ca. 35% and 21 gL−1Day−1, respectively. PMID:24294610

The effect of created local hyperosmotic microenvironment in microcapsule for the growth and metabolism of osmotolerant yeast Candida krusei.

PubMed

Chen, Guo; Yao, Shanjing

2013-01-01

Candida krusei is osmotolerant yeast used for the production of glycerol. Addition of osmolyte such as NaCl into culture medium can increase the production of glycerol from glucose, but osmolytes may burden the glycerol separation. A coencapsulation method was suggested to create local extracellular hyperosmotic stress for glycerol accumulation. Firstly, the influence of osmotic stress induced by the addition of PEG4000 on growth and metabolism of free cell was studied in detail. Glycerol accumulation could be improved by employing PEG4000 as osmoregulator. Secondly, cells and PEG4000 were coentrapped in NaCS/PDMDAAC capsules to create local hyperosmotic stress. The effects of local hyperosmotic microenvironment on the cell growth and metabolism were studied. The coentrapment method increased the glycerol concentration by 25%, and the glycerol concentration attained 50 gL⁻¹ with productivity of 18.8 gL⁻¹Day⁻¹ in shake flask. More importantly, the glycerol could be directly separated from the encapsulated cells. The entrapped cells containing PEG4000 were also cultivated for 15 days in an airlift reactor. The yield and productivity were ca. 35% and 21 gL⁻¹Day⁻¹, respectively.

PEG tubes: dealing with complications.

PubMed

Malhi, Hardip; Thompson, Rosie

A percutaneous endoscopic gastronomy tube can be used to deliver nutrition, hydration and medicines directly into the patient's stomach. Patients will require a tube if they are unable to swallow safely, putting them at risk of aspiration of food, drink and medicines into their lungs. It is vital that nurses are aware of the complications that may arise when caring for a patient with a PEG tube. It is equally important that nurses know how to deal with these complications or from where tc seek advice. This article provides a quick troubleshooting guide to help nurses deal with complications that can arise with PEG feeding.

Ultralow protein adsorbing coatings from clickable PEG nanogel solutions: Benefits of attachment under salt-induced phase separation conditions and comparison with PEG/albumin nanogel coatings

PubMed Central

Donahoe, Casey D.; Cohen, Thomas L.; Li, Wenlu; Nguyen, Peter K.; Fortner, John D.; Mitra, Robi D.; Elbert, Donald L.

2013-01-01

Clickable nanogel solutions were synthesized by using the copper catalyzed azide/alkyne cycloaddition (CuAAC) to partially polymerize solutions of azide and alkyne functionalized poly(ethylene glycol) (PEG) monomers. Coatings were fabricated using a second click reaction: a UV thiol-yne attachment of the nanogel solutions to mercaptosilanated glass. Because the CuAAC reaction was effectively halted by the addition of a copper-chelator, we were able to prevent bulk gelation and limit the coating thickness to a single monolayer of nanogels in the absence of the solution reaction. This enabled the inclusion of kosmotropic salts, which caused the PEG to phase-separate and nearly double the nanogel packing density, as confirmed by Quartz Crystal Microbalance with Dissipation (QCM-D). Protein adsorption was analyzed by single molecule counting with total internal reflection fluorescence (TIRF) microscopy and cell adhesion assays. Coatings formed from the phase-separated clickable nanogel solutions attached with salt adsorbed significantly less fibrinogen than other 100% PEG coatings tested, as well as poly-L-lysine-g-PEG (PLL-g-PEG) coatings. However, PEG/albumin nanogel coatings still outperformed the best 100% PEG clickable nanogel coatings. Additional surface crosslinking of the clickable nanogel coating in the presence of copper further reduced levels of fibrinogen adsorption closer to those of PEG/albumin nanogel coatings. However, this step negatively impacted long-term resistance to cell adhesion and dramatically altered the morphology of the coating by atomic force microscopy (AFM). The main benefit of the click strategy is that the partially polymerized solutions are stable almost indefinitely, allowing attachment in the phase-separated state without danger of bulk gelation, and thus, producing the best performing 100% PEG coating that we have studied to date. PMID:23441808

Synthesis, characterization, and biocompatibility of alternating block polyurethanes based on PLA and PEG.

PubMed

Mei, Tingzhen; Zhu, Yonghe; Ma, Tongcui; He, Tao; Li, Linjing; Wei, Chiju; Xu, Kaitian

2014-09-01

A series of alternating block polyurethanes (abbreviated as PULA-alt-PEG) and random block polyurethanes (abbreviated as PULA-ran-PEG) based on poly(L-lactic acid) (PLA) and poly(ethylene glycol) (PEG) were synthesized. The differences of PULA-alt/ran-PEG chemical structure, molecular weight, distribution, thermal properties, mechanical properties and static contact angle were systematically investigated. The PULA-alt/ran-PEG polyurethanes exhibited low T(g) (-47.3 ∼ -34.4°C), wide mechanical properties (stress σ(t): 4.6-32.6 MPa, modulus E: 11.4-323.9 MPa and strain ε: 468-1530%) and low water contact angle (35.4-51.4°). Scanning electron microscope (SEM) observation showed that PULA-alt-PEG film displays rougher and more patterned surface morphology than PULA-ran-PEG does, due to more regular structures of PULA-alt-PEG. Hydrolytic degradation shows that degradation rate of random block polyurethane series PULA-ran-PEG is higher than the alternating counterpart PULA-alt-PEG. PLA segment degradation is faster than urethane linkage and PEG segment almost does not degrade in the buffer solution. Platelet adhesion study showed that all the polyurethanes possess excellent hemocompatibility. The cell culture assay revealed that PULA-alt/ran-PEG polyurethanes were cell inert and unfavorable for the attachment of rat glial cell due to the hydrophilic characters of the materials. © 2013 Wiley Periodicals, Inc.

Electrospinning synthesis and characterization of PLA-PEG-MNPs composite fibrous membranes

NASA Astrophysics Data System (ADS)

Kumar, M.; Klimke, S.; Preiss, A.; Unruh, D.; Wengerowsky, D.; Lehmann, R.; Sindelar, R.; Klingelhöfer, G.; Boča, R.; Renz, F.

2017-11-01

An electrospinning technique was used to fabricate PLA, PLA-PEG and PLA-PEG-MNPs composite fibrous membranes. The morphology of electrospun composite membranes were characterized by scanning electron microscope. To test the potential availability of MNPs in PLA-PEG composite membranes, TG, Raman, Mössbauer, VSM and ICP-OES analysis were used. The PLA-PEG composite fibrous membranes showed the presence of MNPs, hence offers the possibility for magnetically triggered on-demand drug delivery.

Catching the PEG-induced attractive interaction between proteins.

PubMed

Vivarès, D; Belloni, L; Tardieu, A; Bonneté, F

2002-09-01

We present the experimental and theoretical background of a method to characterize the protein-protein attractive potential induced by one of the mostly used crystallizing agents in the protein-field, the poly(ethylene glycol) (PEG). This attractive interaction is commonly called, in colloid physics, the depletion interaction. Small-Angle X-ray Scattering experiments and numerical treatments based on liquid-state theories were performed on urate oxidase-PEG mixtures with two different PEGs (3350 Da and 8000 Da). A "two-component" approach was used in which the polymer-polymer, the protein-polymer and the protein-protein pair potentials were determined. The resulting effective protein-protein potential was characterized. This potential is the sum of the free-polymer protein-protein potential and of the PEG-induced depletion potential. The depletion potential was found to be hardly dependent upon the protein concentration but strongly function of the polymer size and concentration. Our results were also compared with two models, which give an analytic expression for the depletion potential.

Surveillance Report on SAVY-4000 and Hagan Nuclear Material Storage Containers for FY 2017

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

Reeves, Kirk Patrick; Karns, Tristan; Weis, Eric

In accordance with the SAVY-4000 Surveillance Plan [1] and DOE M441.1-1 requirements, storage container surveillance continued through fiscal year 2017 at Los Alamos National Laboratory. Surveillance items for the year consisted of 8 SAVY-4000 storage containers, 8 Hagan containers, and 39 SAVY-4000 transfer containers. The SAVY-4000 surveillance items ranged in age from 1 year to 5.6 years and the Hagan containers ranged in age from 6.3 years to 17.6 years. The surveillance containers for this year were selected primarily to better understand the extent of corrosion of the stainless steel components of the containers. Accelerated aging studies indicate that themore » O-ring and filter components of the SAVY-4000 will last at least 40 years under LANL storage conditions. However, the observation of corrosion on the inside of SAVY-4000 and Hagan surveillance containers has shifted the emphasis to understanding both the nature and the extent of corrosion on the stainless steel body. The restriction on handling soluble residues greater than 500 grams continued this year, delaying the surveillance of some items that was scheduled in earlier surveillance plans.« less

Electro-spun PLA-PEG-yarns for tissue engineering applications.

PubMed

Kruse, Magnus; Greuel, Marc; Kreimendahl, Franziska; Schneiders, Thomas; Bauer, Benedict; Gries, Thomas; Jockenhoevel, Stefan

2018-06-27

Electro-spinning is widely used in tissue-engineered applications mostly in form of non-woven structures. The development of e-spun yarn opens the door for textile fabrics which combine the micro to nanoscale dimension of electro-spun filaments with three-dimensional (3D) drapable textile fabrics. Therefore, the aim of the study was the implementation of a process for electro-spun yarns. Polylactic acid (PLA) and polyethylene glycol (PEG) were spun from chloroform solutions with varying PLA/PEG ratios (100:0, 90:10, 75:25 and 50:50). The yarn samples produced were analyzed regarding their morphology, tensile strength, water uptake and cytocompatibility. It was found that the yarn diameter decreased when the funnel collector rotation was increasd, however, the fiber diameter was not influenced. The tensile strength was also found to be dependent on the PEG content. While samples composed of 100% PLA showed a tensile strength of 2.5±0.7 cN/tex, the tensile strength increased with a decreasing PLA content (PLA 75%/PEG 25%) to 6.2±0.5 cN/tex. The variation of the PEG content also influenced the viscosity of the spinning solutions. The investigation of the cytocompatibility with endothelial cells was conducted for PLA/PEG 90:10 and 75:25 and indicated that the samples are cytocompatible.

Safety Assessment of Alkyl PEG/PPG Ethers as Used in Cosmetics.

PubMed

Fiume, Monice M; Heldreth, Bart; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan

2016-07-01

The Cosmetic Ingredient Review (CIR) Expert Panel assessed the safety of 131 alkyl polyethylene glycol (PEG)/polypropylene glycol ethers as used in cosmetics, concluding that these ingredients are safe in the present practices of use and concentration described in this safety assessment when formulated to be nonirritating. Most of the alkyl PEG/PPG ethers included in this review are reported to function in cosmetics as surfactants, skin-conditioning agents, and/or emulsifying agents. The alkyl PEG/PPG ethers share very similar physiochemical properties as the alkyl PEG ethers, which were reviewed previously by the CIR Expert Panel and found safe when formulated to be nonirritating. The alkyl PEG ethers differ by the inclusion of PPG repeat units, which are used to fine-tune the surfactant properties of this group. The Panel relied heavily on data on analogous ingredients, extracted from the alkyl PEG ethers and PPG reports, when making its determination of safety. © The Author(s) 2016.

[Efficacy, influencing factors and safety of PEG-INF alpha-2a (PEG-INF-2a) in the treatment of chronic hepatitis C: analysis of 89 patients].

PubMed

Ma, Li-na; Chen, Xin-yue; Chen, Jie; Shen, Cheng-li; Wang, Jun-tao

2006-06-01

To investigate the efficacy, influencing factors and safety of PEG-INF alpha-2a (PEG-INF-2a) in the treatment of hepatitis C. Totally 89 patients with hepatitis C were included in this study and 46 patients were treated with PEG-INF-2a (180 microg or 135 microg/week) and RBV 900 mg/d, 43 patients were treated with IFNalpha-2a (5 MIU/qod) and RBV 900 mg/d. The time of treatment was 48 weeks, and all the patients were visited 24 weeks after treatment. There were no significant differences between the two groups in pretreatment HCV-RNA, HCV genotype and other clinical data. The main parameters to evaluate the efficacy were virological and biochemical responses. The side effects were intensively observed. Sustained virological response (SVR) rate in PEG-IFNalpha-2a group was significantly higher than that in IFNalpha-2a group (56.5% and 19.5% respectively, P<0.001). As the patients were divided according to HCV genotype 1 and high virus load, the SVR rate of PEG-INF alpha-2a group was higher than IFNalpha-2a group (P<0.001). However, there was no significant difference between two groups in the patients with non-genotype 1 and low viral load (P=0.664, 0.116). Similar side-effects were observed in PEG-IFNalpha-2a group and IFNalpha-2a group, but the rate of weight decline and the degree of leukocyte decrease were more significant in PEG-INF alpha-2a group than in IFNalpha-2a group (P=0.001). The efficacy of PEG-INF alpha-2a in the treatment of chronic hepatitis C is superior to that of conventional IFNalpha-2a, PEG-INF alpha-2a had good tolerance and safety profiles.

[Tolerance, safety and efficacy of the one-day preparation of PEG3350 + bisacodyl compared to 2 days of PEG3350 + bisacodyl in pediatric patients].

PubMed

Portillo Canizalez, Ligia Marcela; Blanco Rodriguez, Gerardo; Teyssier Morales, Gustavo; Penchyna Grub, Jaime; Trauernicht Mendieta, Sean; Zurita-Cruz, Jessie Nallely

Multiple intestinal preparations have been used in children undergoing colonoscopy, with variable limitation due to acceptance, tolerance, and proper cleaning. The objective of this study was to compare the tolerability, safety and efficacy of the colonoscopy preparation with 1 day with PEG 3350 (poliethylenglycol) (4g/kg/day) + bisacodyl compared to 2 days of preparation with PEG 3350 (2g/kg/day) + bisacodyl in pediatric patients. A clinical, randomized, and blind trial was performed. Patients aged 2 to 18 years scheduled for colonoscopy were included. Patients were randomized into two groups: 1 day of preparation with PEG 3350 4g/kg/day + bisacodyl and 2 days of preparation with PEG 3350 2g/kg/day + bisacodyl. Through a questionnaire, physical examination and endoscopic evaluation (Boston scale), the tolerance, safety and efficacy of the 2 preparations to be evaluated were determined. Student's t test was performed for quantitative variables and χ 2 for qualitative variables. There were no significant differences in compliance rates, adverse effects, and extent of colonoscopic evaluation. Tolerance and safety between the intestinal preparation for 1-day colonoscopy with PEG 3350 (4g/kg/day) + bisacodyl and the 2-day preparation with PEG 3350 (2g/kg/day) + bisacodyl were similar. The quality of cleanliness was good in both groups, being partially more effective in the 1-day group with PEG 3350 (4g/kg/day). Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Monitoring of RU Peg requested for Swift observations

NASA Astrophysics Data System (ADS)

Waagen, Elizabeth O.

2012-06-01

Dr. Koji Mukai (Universities Space Research Association/NASA Goddard Space Flight Center) has requested AAVSO observers' assistance in monitoring the SS Cyg-type dwarf nova RU Peg in support of target-of-opportunity observations with the NASA Swift satellite during an outburst. His observations will be targeted during the rise to outburst and during late decline from outburst. Thus, your prompt notification to AAVSO Headquarters of activity in RU Peg will be crucial to the success of this campaign. Dr. Mukai writes: "In the famous AAVSO/EUVE/RXTE campaign on SS Cyg (Mattei et al. 2000JAVSO..28..160M), the hard X-ray flux went up (with a delay) during the rise, then suddenly dropped; there was a corresponding flux enhancement episode during the decline. We know that, during the peak of the outburst, many dwarf novae are hard X-ray fainter than in quiescence (with a few exceptions, like U Gem). However, the hard X-ray enhancement episodes seen in SS Cyg have never been obs! erved in other dwarf novae. We have proposed a hypothesis that this is related to the mass of the accreting white dwarf; only dwarf novae with a relatively massive white dwarf show the hard X-ray enhancement. If that's true, we may well see similar enhancement in RU Peg, which is thought to have a massive white dwarf. Even if this hypothesis is completely wrong, RU Peg is a good target for an SS Cyg-like campaign, since it's X-ray bright during quiescence." Visual and CCD observations (filtered preferred to unfiltered) are appropriate for this campaign. Observers are requested to monitor RU Peg duning minimum, throughout the next outburst, and after return to minimym, and report their observations in a timely manner. If RU Peg appears to be brightening from minimum, please report your observations immediately to the AAVSO. If it is brighter than magnitude 12.3, please also send an email report to Elizabeth Waagen (eowaagen@aavso.org) and Matthew Templeton (matthewt@aavso.org). Please be aware that

PEG Enhancement for EM1 and EM2+ Missions

NASA Technical Reports Server (NTRS)

Von der Porten, Paul; Ahmad, Naeem; Hawkins, Matt

2018-01-01

NASA is currently building the Space Launch System (SLS) Block-1 launch vehicle for the Exploration Mission 1 (EM-1) test flight. The next evolution of SLS, the Block-1B Exploration Mission 2 (EM-2), is currently being designed. The Block-1 and Block-1B vehicles will use the Powered Explicit Guidance (PEG) algorithm. Due to the relatively low thrust-to-weight ratio of the Exploration Upper Stage (EUS), certain enhancements to the Block-1 PEG algorithm are needed to perform Block-1B missions. In order to accommodate mission design for EM-2 and beyond, PEG has been significantly improved since its use on the Space Shuttle program. The current version of PEG has the ability to switch to different targets during Core Stage (CS) or EUS flight, and can automatically reconfigure for a single Engine Out (EO) scenario, loss of communication with the Launch Abort System (LAS), and Inertial Navigation System (INS) failure. The Thrust Factor (TF) algorithm uses measured state information in addition to a priori parameters, providing PEG with an improved estimate of propulsion information. This provides robustness against unknown or undetected engine failures. A loft parameter input allows LAS jettison while maximizing payload mass. The current PEG algorithm is now able to handle various classes of missions with burn arcs much longer than were seen in the shuttle program. These missions include targeting a circular LEO orbit with a low-thrust, long-burn-duration upper stage, targeting a highly eccentric Trans-Lunar Injection (TLI) orbit, targeting a disposal orbit using the low-thrust Reaction Control System (RCS), and targeting a hyperbolic orbit. This paper will describe the design and implementation of the TF algorithm, the strategy to handle EO in various flight regimes, algorithms to cover off-nominal conditions, and other enhancements to the Block-1 PEG algorithm. This paper illustrates challenges posed by the Block-1B vehicle, and results show that the improved PEG

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

PubMed

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

2007-01-01

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

Unique regulatory properties of the UDP-glucose:. beta. -1,4-glucan synthetase of Acetobacter xylinum. [Acetobacter xylinum

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

Benziman, M.; Aloni, Y.; Delmer, D.P.

1983-01-01

Conditions have been found for an extremely efficient transfer of glucose from UDP-glucose to a cellulosic ..beta..-1,4-glucan product, using enzyme preparations derived from cells of Acetobacter xylinum. Membrane fractions obtained by rupturing cells in the presence of 20% (w/v) polyethylene glycol-4000 (PEG-4000) exhibited UDP-glucose:..beta..-1,4-glucan synthetase activity 3- to 10-fold higher than those previously reported. Enzyme prepared in this fashion also shows a further marked activation by GTP. The activation (apparent K/sub alpha/ = 35 ..mu..M) is quite specific for GTP. A variety of other nucleotides and nucleotide derivatives had no effect on activity. Guanosine-5'-(lambda-thio)triphosphate, an analog of GTP, is evenmore » more efficient than GTP (K/sub alpha/ = 17 ..mu..M). Enzyme prepared in the absence of PEG-4000 does not respond to GTP because it lacks a protein factor essential for GTP activation. PEG-4000 promotes the interaction of the protein factor with the enzyme. The factor itself is devoid of synthetase activity and does not stimulate activity of the enzyme in the absence of GTP. Under optimal conditions, in the presence of GTP, factor, and PEG-4000, initial rates of enzyme activity that are 200 times higher than those previously reported can be achieved. Such rates exceed 40% of the in vivo rate of cellulose synthesis from glucose. 26 references, 3 figures, 3 tables.« less

Antitumor Effect of GO-PEG-DOX Complex on EMT-6 Mouse Breast Cancer Cells.

PubMed

Yan, Jinyin; Song, Bo; Hu, Wanning; Meng, Ying; Niu, Fengling; Han, Xiaochen; Ge, Yuhui; Li, Ning

2018-05-01

Doxorubicin (DOX) can be used to treat malignant tumors, but with multiple adverse effects. Graphene oxide-polyethylene glycol (GO-PEG) is a novel nanoscale carrier material and can elevate solubility and biocompatibility of drugs. This study prepared a GO-PEG-DOX complex, whose toxicity and antitumor effects were evaluated on mouse EMT-6 breast cancer cells. GO-PEG-DOX complex was prepared for calculating the drug carrier rate of DOX on GO-PEG by MV approach. EMT-6 cells were treated with 40 μg/mL GO-PEG, 1 μg/mL DOX, or 40 μg/mL +1 μg/mL GO-PEG-DOX for 72 h of incubation. Cells without treatment were considered the control group. Cell survival rate and apoptotic rate were tested at different time points. GO-PEG and GO-PEG-DOX complex were successfully prepared with satisfactory solubility. After 72 h of incubation, EMT-6 cells after GO-PEG-DOX treatment had significantly higher survival rate than GO-PEG group (p < 0.05). All three treatment groups had significantly elevated apoptotic rates than control group (p < 0.05). GO-PEG-DOX group had much more apoptosis (p < 0.05 compared with DOX group). Moreover, with elongated treatment time, all groups showed decreased survival rate (p < 0.05). GO-PEG did not reduce the cytotoxicity of DOX on EMT-6 cells. GO-PEG-DOX complex can increase the water solubility and targeting sensitivity of DOX, with facilitating effects on DOX-induced tumor cell apoptosis.

Safety Assessment of Alkyl PEG Sulfosuccinates as Used in Cosmetics.

PubMed

Johnson, Wilbur; Heldreth, Bart; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan

2015-09-01

The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) reviewed the safety of alkyl polyethylene glycol (PEG) sulfosuccinates, which function in cosmetics mostly as surfactants/cleansing agents. Although these ingredients may cause ocular and skin irritation, dermal penetration is unlikely because of the substantial polarity and molecular size of these ingredients. The Panel considered the negative oral carcinogenicity and reproductive and developmental toxicity data on chemically related laureths (PEG lauryl ethers) and negative repeated dose toxicity and skin sensitization data on disodium laureth sulfosuccinate supported the safety of these alkyl PEG sulfosuccinates in cosmetic products, but. The CIR Expert Panel concluded that the alkyl PEG sulfosuccinates are safe in the present practices of use and concentration when formulated to be nonirritating. © The Author(s) 2015.

Bioactive Hydrogels Made from Step-Growth Derived PEG-Peptide Macromers

PubMed Central

Miller, Jordan S.; Shen, Colette J.; Legant, Wesley R.; Baranski, Jan D.; Blakely, Brandon L.; Chen, Christopher S.

2010-01-01

Synthetic hydrogels based on poly(ethylene glycol) (PEG) have been used as biomaterials for cell biology and tissue engineering investigations. Bioactive PEG-based gels have largely relied on heterobifunctional or multi-arm PEG precursors that can be difficult to synthesize and characterize or expensive to obtain. Here, we report an alternative strategy, which instead uses inexpensive and readily available PEG precursors to simplify reactant sourcing. This new approach provides a robust system in which to probe cellular interactions with the microenvironment. We used the step-growth polymerization of PEG diacrylate (PEGDA, 3400 Da) with bis-cysteine matrix metalloproteinase (MMP)-sensitive peptides via Michael-type addition to form biodegradable photoactive macromers of the form acrylate-PEG-(peptide-PEG)m-acrylate. The molecular weight (MW) of these macromers is controlled by the stoichiometry of the reaction, with a high proportion of resultant macromer species greater than 500 kDa. In addition, the polydispersity of these materials was nearly identical for three different MMP-sensitive peptide sequences subjected to the same reaction conditions. When photopolymerized into hydrogels, these high MW materials exhibit increased swelling and sensitivity to collagenase-mediated degradation as compared to previously published PEG hydrogel systems. Cell-adhesive acrylate-PEG-CGRGDS was synthesized similarly and its immobilization and stability in solid hydrogels was characterized with a modified Lowry assay. To illustrate the functional utility of this approach in a biological setting, we applied this system to develop materials that promote angiogenesis in an ex vivo aortic arch explant assay. We demonstrate the formation and invasion of new sprouts mediated by endothelial cells into the hydrogels from embedded embryonic chick aortic arches. Furthermore, we show that this capillary sprouting and three-dimensional migration of endothelial cells can be tuned by

Structural analysis of binding functionality of folic acid-PEG dendrimers against folate receptor.

PubMed

Sampogna-Mireles, Diana; Araya-Durán, Ingrid D; Márquez-Miranda, Valeria; Valencia-Gallegos, Jesús A; González-Nilo, Fernando D

2017-03-01

Dendrimers functionalized with folic acid (FA) are drug delivery systems that can selectively target cancer cells with folate receptors (FR-α) overexpression. Incorporation of polyethylene glycol (PEG) can enhance dendrimers solubility and pharmacokinetics, but ligand-receptor binding must not be affected. In this work we characterized, at atomic level, the binding functionality of conventional site-specific dendrimers conjugated with FA with PEG 750 or PEG 3350 as a linker. After Molecular Dynamics simulation, we observed that both PEG's did not interfere over ligand-receptor binding functionality. Although binding kinetics could be notably affected, the folate fragment from both dendrimers remained exposed to the solvent before approaching selectively to FR-α. PEG 3350 provided better solubility and protection from enzymatic degradation to the dendrimer than PEG 750. Also, FA-PEG3350 dendrimer showed a slightly better interaction with FR-α than FA-PEG750 dendrimer. Therefore, theoretical evidence supports that both dendrimers are suitable as drug delivery systems for cancer therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

Lamellar, micro-phase separated blends of methyl cellulose and dendritic polyethylene glycol, POSS-PEG.

PubMed

Chinnam, Parameswara Rao; Mantravadi, Ramya; Jimenez, Jayvic C; Dikin, Dmitriy A; Wunder, Stephanie L

2016-01-20

Blends of methyl cellulose (MC) and liquid pegylated polyoctahedralsilsesquioxane (POSS-PEG) were prepared from non-gelled, aqueous solutions at room temperature (RT), which was below their gel temperatures (Tm). Lamellar, fibrillated films (pure MC) and increasingly micro-porous morphologies with increasing POSS-PEG content were formed, which had RT moduli between 1 and 5GPa. Evidence of distinct micro-phase separated MC and POSS-PEG domains was indicated by the persistence of the MC and POSS-PEG (at 77K) crystal structures in the X-ray diffraction data, and scanning transmission electron images. Mixing of MC and POSS-PEG in the interface region was indicated by suppression of crystallinity in the POSS-PEG, and increases/decreases in the glass transition temperatures (Tg) of POSS-PEG/MC in the blends compared with the pure components. These interface interactions may serve as cross-link sites between the micro-phase separated domains that permit incorporation of high amounts of POSS-PEG in the blends, prevent macro-phase separation and result in rubbery material properties (at high POSS-PEG content). Above Tg/Tm of POSS-PEG, the moduli of the blends increase with MC content as expected. However, below Tg/Tm of POSS-PEG, the moduli are greater for blends with high POSS-PEG content, suggesting that it behaves like semi-crystalline polyethylene oxide reinforced with silica (SiO1.5). Copyright © 2015 Elsevier Ltd. All rights reserved.

PEG-lipid micelles as drug carriers: physiochemical attributes, formulation principles and biological implication.

PubMed

Gill, Kanwaldeep K; Kaddoumi, Amal; Nazzal, Sami

2015-04-01

PEG-lipid micelles, primarily conjugates of polyethylene glycol (PEG) and distearyl phosphatidylethanolamine (DSPE) or PEG-DSPE, have emerged as promising drug-delivery carriers to address the shortcomings associated with new molecular entities with suboptimal biopharmaceutical attributes. The flexibility in PEG-DSPE design coupled with the simplicity of physical drug entrapment have distinguished PEG-lipid micelles as versatile and effective drug carriers for cancer therapy. They were shown to overcome several limitations of poorly soluble drugs such as non-specific biodistribution and targeting, lack of water solubility and poor oral bioavailability. Therefore, considerable efforts have been made to exploit the full potential of these delivery systems; to entrap poorly soluble drugs and target pathological sites both passively through the enhanced permeability and retention (EPR) effect and actively by linking the terminal PEG groups with targeting ligands, which were shown to increase delivery efficiency and tissue specificity. This article reviews the current state of PEG-lipid micelles as delivery carriers for poorly soluble drugs, their biological implications and recent developments in exploring their active targeting potential. In addition, this review sheds light on the physical properties of PEG-lipid micelles and their relevance to the inherent advantages and applications of PEG-lipid micelles for drug delivery.

Physiologically based pharmacokinetic modeling of PLGA nanoparticles with varied mPEG content

PubMed Central

Li, Mingguang; Panagi, Zoi; Avgoustakis, Konstantinos; Reineke, Joshua

2012-01-01

Biodistribution of nanoparticles is dependent on their physicochemical properties (such as size, surface charge, and surface hydrophilicity). Clear and systematic understanding of nanoparticle properties’ effects on their in vivo performance is of fundamental significance in nanoparticle design, development and optimization for medical applications, and toxicity evaluation. In the present study, a physiologically based pharmacokinetic model was utilized to interpret the effects of nanoparticle properties on previously published biodistribution data. Biodistribution data for five poly(lactic-co-glycolic) acid (PLGA) nanoparticle formulations prepared with varied content of monomethoxypoly (ethyleneglycol) (mPEG) (PLGA, PLGA-mPEG256, PLGA-mPEG153, PLGA-mPEG51, PLGA-mPEG34) were collected in mice after intravenous injection. A physiologically based pharmacokinetic model was developed and evaluated to simulate the mass-time profiles of nanoparticle distribution in tissues. In anticipation that the biodistribution of new nanoparticle formulations could be predicted from the physiologically based pharmacokinetic model, multivariate regression analysis was performed to build the relationship between nanoparticle properties (size, zeta potential, and number of PEG molecules per unit surface area) and biodistribution parameters. Based on these relationships, characterized physicochemical properties of PLGA-mPEG495 nanoparticles (a sixth formulation) were used to calculate (predict) biodistribution profiles. For all five initial formulations, the developed model adequately simulates the experimental data indicating that the model is suitable for description of PLGA-mPEG nanoparticle biodistribution. Further, the predicted biodistribution profiles of PLGA-mPEG495 were close to experimental data, reflecting properly developed property–biodistribution relationships. PMID:22419876

Development practices and lessons learned in developing SimPEG

NASA Astrophysics Data System (ADS)

Cockett, R.; Heagy, L. J.; Kang, S.; Rosenkjaer, G. K.

2015-12-01

Inverse modelling provides a mathematical framework for constructing a model of physical property distributions in the subsurface that are consistent with the data collected in geophysical surveys. The geosciences are increasingly moving towards the integration of geological, geophysical, and hydrological information to better characterize the subsurface. This integration must span disciplines and is not only challenging scientifically, but additionally the inconsistencies between conventions often makes implementations complicated, non­ reproducible, or inefficient. SimPEG is an open-source, multi-university effort aimed at providing a generalized framework for solving forward and inverse problems. SimPEG includes finite volume discretizations on structured and unstructured meshes, interfaces to standard numerical solver packages, convex optimization algorithms, model parameterizations, and visualization routines. The SimPEG package (http://simpeg.xyz) supports an ecosystem of forward and inverse modelling applications, including electromagnetics, vadose zone flow, seismic, and potential­ fields, that are all written with a common interface and toolbox. The goal of SimPEG is to support a community of researchers with well-tested, extensible tools, and encourage transparency and reproducibility both of the SimPEG software and the geoscientific research it is applied to. In this presentation, we will share some of the lessons we have learned in designing the modular infrastructure, testing and development practices of SimPEG. We will discuss our use of version control, extensive unit-testing, continuous integration, documentation, issue tracking, and resources that facilitate communication between existing team members and allows new researchers to get involved. These practices have enabled the use of SimPEG in research, industry, and education as well as the ability to support a growing number of dependent repositories and applications. We hope that sharing our

Accurate measurements of solar spectral irradiance between 4000-10000 cm-1

NASA Astrophysics Data System (ADS)

Elsey, J.; Coleman, M. D.; Gardiner, T.; Shine, K. P.

2017-12-01

The near-infrared solar spectral irradiance (SSI) is an important input into simulations of weather and climate; the distribution of energy throughout this region of the spectrum influences atmospheric heating rates and the global hydrological cycle through absorption and scattering by water vapour. Current measurements by a mixture of ground-based and space-based instruments show differences of around 10% in the 4000-7000 cm-1 region, with no resolution to this controversy in sight. This work presents observations of SSI taken using a ground-based Fourier Transform spectrometer between 4000-10000 cm-1 at a field site in Camborne, UK, with particular focus on a rigorously defined uncertainty budget. While there is good agreement between this work and the commonly-used ATLAS3 spectrum between 7000-10000 cm-1, the SSI is systematically lower by 10% than ATLAS3 between 4000-7000 cm-1, with no overlap within the k = 2 measurement uncertainties.

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

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

Abebe, Daniel G.; Fujiwara, Tomoko

2012-09-05

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

Los Alamos National Laboratory SAVY-4000 Field Surveillance Plan Update for 2016

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

Kelly, Elizabeth J.; Stone, Timothy Amos; Smith, Paul Herrick

The Packaging Surveillance Program section of the Department of Energy (DOE) Manual 441.1-1, Nuclear Material Packaging Manual (DOE 2008), requires DOE contractors to “ensure that a surveillance program is established and implemented to ensure the nuclear material storage package continues to meet its design criteria.” The Los Alamos National Laboratory (LANL) SAVY-4000 Field Surveillance Plan was first issued in FY 2013 (Kelly et al. 2013). The surveillance plan is reviewed annually and updated as necessary based on SAVY-4000 surveillance and other surveillance findings, as well as results of the lifetime extension studies (Blair et al. 2012, Weis et al. 2015a).more » The LANL SAVY-4000 Field Surveillance Plan Update was issued in 2014 (Kelly et al. 2014). This 2016 update reflects changes to the surveillance plan resulting from restrictions on handling residue materials greater than 500 g, the addition of specific engineering judgment containers, and 2015 surveillance findings. The SAVY-4000 container has a design life of five years, which was chosen as a conservative estimate of the functional properties of the materials used in the construction of the SAVY 4000 when exposed to the potential insults including temperature, corrosive materials and gases, and radiation. The SAVY-4000 container design basis is described in a safety analysis report (Anderson et al. 2013). In the National Nuclear Security Administration's (NNSA’s) approval of the safety analysis report, it was recommended that the design life clock begin on March 2014 (Nez et al. 2014). However, it is expected that a technical basis can be developed to extend the design life of the SAVY-4000 containers to approximately 40 years (Blair et al. 2012, Weis et al. 2015a). This surveillance plan update covers five years (2015–2019) and is developed to ensure SAVY-4000 containers meet their design criteria over the current five-year design life and to gather data that can be used in developing the

Some observations on the nature of the audiometric 4000 hz notch: data from 3430 veterans.

PubMed

Wilson, Richard H

2011-01-01

Pure-tone, air-conduction audiograms notched at 4000 Hz have long been considered the signature configuration for noise-induced hearing loss even though there is an extensive literature that does not mesh with this simple explanation. There are many reports of notched audiograms from individuals with no history of noise exposure and, conversely, reports of audiograms with no notches from individuals with a history of noise exposure. Recent reports increasingly suggest that unilateral 4000 Hz notches are common. The prevalence of notched audiograms at 4000 Hz is dependent on the definition of the notch and the population under study. To examine the prevalence and characteristics of audiograms that are notched at 4000 Hz. Retrospective, descriptive. The participants were 3430 veterans evaluated in the Audiology Clinic at the VA Medical Center, Mountain Home, Tennessee. The mean age was 62.3 yr. Data Collection and Analyses: The data were collected in the course of a 60 min, routine audiological evaluation. In addition to pure-tone audiometry, a history, otoscopy, speech audiometry in quiet and in noise, and aural-acoustic immittance measures were included in the clinic protocol but were not evaluated in this report. A notch was defined when the 4000 Hz threshold minus the 2000 Hz threshold and the 4000 Hz threshold minus the 8000 Hz threshold both were ≥10 dB. Overall the mean LE (left ear) thresholds at 2000, 3000, and 4000 Hz were at hearing levels 2-3 dB higher than the hearing levels for the corresponding mean RE (right ear) thresholds; the differences were significant. A notched audiogram was observed in 40.6% of the participants in at least one ear with 15.4% having bilateral notches, 28.8% LE notches, and 27.1% RE notches. Unilateral 4000 Hz notches were almost twice as prevalent as bilateral 4000 Hz notches. Viewed as a function of age, notched audiograms were most common (∼35% of the participants) in the 40 and 50 yr groups with a diminishing prevalence

Transferrin-mediated targeting of hypericin embedded in sterically stabilized PEG-liposomes.

PubMed

Derycke, Annelies S L; De Witte, Peter A M

2002-01-01

Over the last few decades, photodynamic therapy evolved to a promising new treating modality for cancer. The photosensitizers used, induce light sensitivity to a normal light insensitive chemical or physical process. Third generation photosensitizers are derivatives of second generation photosensitizers introduced into or attached to chemical devices. This modification increases the biological specificity to deliver photosensitizers to a defined cell type. The aim of this study was to improve the specificity of hypericin for tumor cells using transferrin-conjugated PEG-liposomes. Transferrin was used as tumor-seeking molecule, since many tumor cells, among which HeLa cells, overexpress transferrin receptors on their surface. Hypericin, a potent second generation photosensitizer, was integrated in the lipid bilayers of the liposomes. The antiproliferative effect of the targeted PEG-liposomes was determined and compared with the results of non-targeted PEG-liposomes and free hypericin. Additionally, the intracellular accumulation assay was performed. All manipulations were done on HeLa cells. To interpret the results, the data were supplemented by findings concerning embedding stability. Targeting hypericin by transferrin-conjugated PEG-liposomes did not significantly favour the photocytotoxicity and the intracellular accumulation of hypericin, in comparison with non-targeted PEG-liposomes or free hypericin. Embedding stability experiments showed only limited stable embedding. Despite of their proven efficiency as a targeting carrier system, transferrin-conjugated PEG-liposomes seem less effective in targeting hypericin to tumor cells due to the amount of hypericin leaking out of the PEG-liposomes.

Crystalline polyoxometalate (POM)–polyethylene glycol (PEG) composites aimed as non-humidified intermediate-temperature proton conductors

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

Tsuboi, Masaki; Hibino, Mitsuhiro; Mizuno, Noritaka

2016-02-15

Crystalline polyoxometalate (POM)–polyethylene glycol (PEG) composites aimed as non-humidified intermediate-temperature proton conductors were synthesized and characterized by single crystal and powder XRD, solid state MASNMR, and TG-DTA measurements. Among the POM–PEG composites, Cs{sub 2.7}H{sub 0.3}[PW{sub 12}O{sub 40}]·1.2PEG1000 (CsHPW-PEG1000) possessed one-dimensional channels with diameters of ca. 6 and 8 Å, where PEG probably resided, and showed the best performance as a proton conductor (1.2×10{sup −5} S cm{sup −1} at 443 K). Proton conductivities of POM–PEG composites decreased by the increase in molecular weights of PEG (CsHPW-PEG12,000) or anion charges (CsHSiW-PEG1000). Variable contact time {sup 13}C-CP (cross polarization) MASNMR revealed that localmore » mobility (i.e., segmental motion) of PEG is related to the trends in proton conductivities. These results show that amount of acidic protons (H{sup +}) is not the primary factor in proton conduction and that segmental motion of PEG assists the proton hopping among POMs in the crystal lattice of POM–PEG composites. - Graphical abstract: Non-humidified intermediate-temperature proton conduction in crystalline polyoxometalate (POM)–polyethylene (PEG) composites are assisted by the segmental motion of PEG. - Highlights: • Crystalline polyoxometalate–polyethlene glycol (PEG) composites were synthesized. • CsHPW-PEG1000 possessed one-dimensional channels and showed the highest proton conductivity. • {sup 13}C CPMASNMR revealed that segmental motion of PEG is related to the proton conduction.« less

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

PubMed

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

2013-06-01

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

Correlation between Colon Transit Time Test Value and Initial Maintenance Dose of Laxative in Children with Chronic Functional Constipation

PubMed Central

Kim, Mock Ryeon; Park, Hye Won; Son, Jae Sung; Lee, Ran

2016-01-01

Purpose To evaluate the correlation between colon transit time (CTT) test value and initial maintenance dose of polyethylene glycol (PEG) 4000 or lactulose. Methods Of 415 children with chronic functional constipation, 190 were enrolled based on exclusion criteria using the CTT test, defecation diary, and clinical chart. The CTT test was performed with prior disimpaction. The laxative dose for maintenance was determined on the basis of the defecation diary and clinical chart. The Shapiro-Wilk test and Pearson's and Spearman's correlations were used for statistical analysis. Results The overall group median value and interquartile range of the CTT test was 43.8 (31.8) hours. The average PEG 4000 dose for maintenance in the overall group was 0.68±0.18 g/kg/d; according to age, the dose was 0.73±0.16 g/kg/d (<8 years), 0.53±0.12 g/kg/d (8 to <12 years), and 0.36±0.05 g/kg/d (12 to 15 years). The dose of lactulose was 1.99±0.43 mL/kg/d (<8 years) or 1.26±0.25 mL/kg/d (8 to <12 years). There was no significant correlation between CTT test value and initial dose of laxative, irrespective of the subgroup (encopresis, abnormal CTT test subtype) for either laxative. Even in the largest group (overall, n=109, younger than 8 years and on PEG 4000), the correlation was weak (Pearson's correlation coefficient [R]=0.268, p=0.005). Within the abnormal transit group, subgroup (n=73, younger than 8 years and on PEG 4000) correlation was weak (R=0.267, p=0.022). Conclusion CTT test value cannot predict the initial maintenance dose of PEG 4000 or lactulose with linear correlation. PMID:27738600

Correlation between Colon Transit Time Test Value and Initial Maintenance Dose of Laxative in Children with Chronic Functional Constipation.

PubMed

Kim, Mock Ryeon; Park, Hye Won; Son, Jae Sung; Lee, Ran; Bae, Sun Hwan

2016-09-01

To evaluate the correlation between colon transit time (CTT) test value and initial maintenance dose of polyethylene glycol (PEG) 4000 or lactulose. Of 415 children with chronic functional constipation, 190 were enrolled based on exclusion criteria using the CTT test, defecation diary, and clinical chart. The CTT test was performed with prior disimpaction. The laxative dose for maintenance was determined on the basis of the defecation diary and clinical chart. The Shapiro-Wilk test and Pearson's and Spearman's correlations were used for statistical analysis. The overall group median value and interquartile range of the CTT test was 43.8 (31.8) hours. The average PEG 4000 dose for maintenance in the overall group was 0.68±0.18 g/kg/d; according to age, the dose was 0.73±0.16 g/kg/d (<8 years), 0.53±0.12 g/kg/d (8 to <12 years), and 0.36±0.05 g/kg/d (12 to 15 years). The dose of lactulose was 1.99±0.43 mL/kg/d (<8 years) or 1.26±0.25 mL/kg/d (8 to <12 years). There was no significant correlation between CTT test value and initial dose of laxative, irrespective of the subgroup (encopresis, abnormal CTT test subtype) for either laxative. Even in the largest group (overall, n=109, younger than 8 years and on PEG 4000), the correlation was weak (Pearson's correlation coefficient [R]=0.268, p =0.005). Within the abnormal transit group, subgroup (n=73, younger than 8 years and on PEG 4000) correlation was weak (R=0.267, p =0.022). CTT test value cannot predict the initial maintenance dose of PEG 4000 or lactulose with linear correlation.

Analysis of PEG oligomers in black gel inks: Discrimination and ink dating.

PubMed

Sun, Qiran; Luo, Yiwen; Xiang, Ping; Yang, Xu; Shen, Min

2017-08-01

Carbon-based black gel inks are common samples in forensic practice of questioned document examination in China, but there are few analytical methods for this type of ink. In this study, a liquid chromatography-.high resolution mass spectrometry (LC-HRMS) method was established for the analysis of PEG oligomers in carbon-based black gel ink entries. The coupled instruments achieve both the identification and quantification of PEG oligomers in ink entries with reproducible results. Twenty carbon-based black gel inks, whose Raman spectra appeared identical, were analyzed using the LC-HRMS method. As a result, the twenty gel inks were classified into four groups according to the distribution of PEG oligomers. Artificially aging of PEG 400 and a gel ink showed that as PEG degraded, the relative amounts of low molecular weight PEG oligomers increased, while those of high molecular weight decreased. The degradation of PEG oligomers in a naturally aged gel ink was consistent with those in the artificially aged samples, but occurred more slowly. This study not only provided a new method for discriminating carbon-based black gel ink entries, but also offered a new approach for studying the relative ink dating of carbon-based black gel ink entries. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthesis and characterization of PEG-P(MAA-SS-VCL) nanoparticles

NASA Astrophysics Data System (ADS)

Yu, L. L.; Yang, K.; Mu, R. H.; Zhang, N.; Su, L.

2016-07-01

The PEG-P(MAA-SS-VCL) nanoparticles were obtained using disulfide containing dimethacrylate (SS) as cross-linking agent, using polyethylene glycol methyl acrylate (PEGMA), N-Vinyl-ε-caprolactam (VCL), and methacrylic acid (MAA) as monomers via homogeneous polymerization in aqueous. The PEG-P(MAA-SS-VCL) nanoparticles were characterized by FT-IR and TGA. The particle size and morphology variation in different environments were detected by dynamic light scattering (DLS) and scanning electron microscopy (SEM). It is the very method that PEG-P(MAA-SS-VCL) nanoparticles can be obtained in this study.

Pore structure modified diatomite-supported PEG composites for thermal energy storage

NASA Astrophysics Data System (ADS)

Qian, Tingting; Li, Jinhong; Deng, Yong

2016-09-01

A series of novel composite phase change materials (PCMs) were tailored by blending PEG and five kinds of diatomite via a vacuum impregnation method. To enlarge its pore size and specific surface area, different modification approaches including calcination, acid treatment, alkali leaching and nano-silica decoration on the microstructure of diatomite were outlined. Among them, 8 min of 5 wt% NaOH dissolution at 70 °C has been proven to be the most effective and facile. While PEG melted during phase transformation, the maximum load of PEG could reach 70 wt.%, which was 46% higher than that of the raw diatomite. The apparent activation energy of PEG in the composite was 1031.85 kJ·mol-1, which was twice higher than that of the pristine PEG. Moreover, using the nano-silica decorated diatomite as carrier, the maximum PEG load was 66 wt%. The composite PCM was stable in terms of thermal and chemical manners even after 200 cycles of melting and freezing. All results indicated that the obtained composite PCMs were promising candidate materials for building applications due to its large latent heat, suitable phase change temperature, excellent chemical compatibility, improved supercooling extent, high thermal stability and long-term reliability.

Pore structure modified diatomite-supported PEG composites for thermal energy storage

PubMed Central

Qian, Tingting; Li, Jinhong; Deng, Yong

2016-01-01

A series of novel composite phase change materials (PCMs) were tailored by blending PEG and five kinds of diatomite via a vacuum impregnation method. To enlarge its pore size and specific surface area, different modification approaches including calcination, acid treatment, alkali leaching and nano-silica decoration on the microstructure of diatomite were outlined. Among them, 8 min of 5 wt% NaOH dissolution at 70 °C has been proven to be the most effective and facile. While PEG melted during phase transformation, the maximum load of PEG could reach 70 wt.%, which was 46% higher than that of the raw diatomite. The apparent activation energy of PEG in the composite was 1031.85 kJ·mol−1, which was twice higher than that of the pristine PEG. Moreover, using the nano-silica decorated diatomite as carrier, the maximum PEG load was 66 wt%. The composite PCM was stable in terms of thermal and chemical manners even after 200 cycles of melting and freezing. All results indicated that the obtained composite PCMs were promising candidate materials for building applications due to its large latent heat, suitable phase change temperature, excellent chemical compatibility, improved supercooling extent, high thermal stability and long-term reliability. PMID:27580677

Pore structure modified diatomite-supported PEG composites for thermal energy storage.

PubMed

Qian, Tingting; Li, Jinhong; Deng, Yong

2016-09-01

A series of novel composite phase change materials (PCMs) were tailored by blending PEG and five kinds of diatomite via a vacuum impregnation method. To enlarge its pore size and specific surface area, different modification approaches including calcination, acid treatment, alkali leaching and nano-silica decoration on the microstructure of diatomite were outlined. Among them, 8 min of 5 wt% NaOH dissolution at 70 °C has been proven to be the most effective and facile. While PEG melted during phase transformation, the maximum load of PEG could reach 70 wt.%, which was 46% higher than that of the raw diatomite. The apparent activation energy of PEG in the composite was 1031.85 kJ·mol(-1), which was twice higher than that of the pristine PEG. Moreover, using the nano-silica decorated diatomite as carrier, the maximum PEG load was 66 wt%. The composite PCM was stable in terms of thermal and chemical manners even after 200 cycles of melting and freezing. All results indicated that the obtained composite PCMs were promising candidate materials for building applications due to its large latent heat, suitable phase change temperature, excellent chemical compatibility, improved supercooling extent, high thermal stability and long-term reliability.

Adsorption of polyethylene glycol (PEG) onto cellulose nano-crystals to improve its dispersity.

PubMed

Cheng, Dong; Wen, Yangbing; Wang, Lijuan; An, Xingye; Zhu, Xuhai; Ni, Yonghao

2015-06-05

In this work, the adsorption of polyethylene glycol (PEG) onto cellulose nano-crystals (CNC) was investigated for preparing re-dispersible dried CNC. Results showed that the re-dispersity of CNC in water can be significantly enhanced using a PEG1000 dosage of 5wt% (based on the dry weight of CNC). The elemental analysis confirmed the adsorption of PEG onto the CNC surface. Transmission electron microscopy (TEM) was used to characterize the dry powder and indicated that the irreversible agglomeration of CNC after drying was essentially eliminated based on the PEG adsorption concept. Thermo-gravimetric analysis (TGA) and X-ray diffraction (XRD) suggested that CNC crystallinity and thermal stability were not affected by the adsorption of PEG. Thus, the adsorption of PEG has great potential for producing re-dispersible powder CNC. Copyright © 2015 Elsevier Ltd. All rights reserved.

PEG-stearate coated solid lipid nanoparticles as levothyroxine carriers for oral administration

NASA Astrophysics Data System (ADS)

Kashanian, Soheila; Rostami, Elham

2014-03-01

In this study, poly ethylene glycol 100 stearate (PEG 100-S) was used to prepare coated solid lipid nanoparticles with loading levothyroxine sodium (levo-loaded PEG 100-S-coated SLNs) by microemulsification technique. Evaluation of the release kinetic of prepared colloidal carriers was conducted. The particle size and zeta potential of levo-loaded PEG 100-S-coated SLNs have been measured to be 187.5 nm and -23.0 mV, respectively, using photon correlation spectroscopy (PCS). Drug entrapment efficiency (EE) was calculated to be 99 %. Differential scanning calorimetry indicated that the majority of drug loaded in PEG 100-S-coated SLNs were in amorphous state which could be considered desirable for drug delivery. The purpose of this study was to develop a new nanoparticle system, consisting lipid nanoparticles coated with PEG 100-S. The modification procedure led to a reduction in the zeta potential values, varying from -40.0 to -23.0 mV for the uncoated and PEG-coated SLNs, respectively. Stability results of the nanoparticles in gastric and intestinal media show that the low pH of the gastric medium is responsible for the critical aggregation and degradation of the uncoated lipid nanoparticles. PEG 100-S-coated SLNs were more stable due to their polymer coating layer which prevented aggregation of SLNs. Consequently, it is possible that the PEG surrounds the particles reducing the attachment of enzymes and further degradation of the triglyceride cores. Shape and surface morphology of particles were determined by transition electron microscopy and scanning electron microscopy that revealed spherical shape of nanoparticles. In vitro drug release of PEG 100-S-coated SLNs was characterized using diffusion cell which showed a controlled release for drug.

Physicochemical characterization of spray-dried PLGA/PEG microspheres, and preliminary assessment of biological response.

PubMed

Javiya, Curie; Jonnalagadda, Sriramakamal

2016-09-01

The use of spray-drying to prepare blended PLGA:PEG microspheres with lower immune detection. To study physical properties, polymer miscibility and alveolar macrophage response for blended PLGA:PEG microspheres prepared by a laboratory-scale spray-drying process. Microspheres were prepared by spray-drying 0-20% w/w ratios of PLGA 65:35 and PEG 3350 in dichloromethane. Particle size and morphology was studied using scanning electron microscopy. Polymer miscibility and residual solvent levels evaluated by thermal analysis (differential scanning calorimetry - DSC and thermogravimetric analysis - TGA). Immunogenicity was assessed in vitro by response of rat alveolar macrophages (NR8383) by the MTT-based cell viability assay and reactive oxygen species (ROS) detection. The spray dried particles were spherical, with a size range of about 2-3 µm and a yield of 16-60%. Highest yield was obtained at 1% PEG concentration. Thermal analysis showed a melting peak at 59 °C (enthalpy: 170.61 J/g) and a degradation-onset of 180 °C for PEG 3350. PLGA 65:35 was amorphous, with a Tg of 43 °C. Blended PLGA:PEG microspheres showed a delayed degradation-onset of 280 °C, and PEG enthalpy-loss corresponding to 15% miscibility of PEG in PLGA. NR8383 viability studies and ROS detection upon exposure to these cells suggested that blended PLGA:PEG microspheres containing 1 and 5% PEG are optimal in controling cell proliferation and activation. This research establishes the feasibility of using a spray-drying process to prepare spherical particles (2-3 µm) of molecularly-blended PLGA 65:35 and PEG 3350. A PEG concentration of 1-5% was optimal to maximize process yield, with minimal potential for immune detection.

The Osteogenesis of Bone Marrow Stem Cells on mPEG-PCL-mPEG/Hydroxyapatite Composite Scaffold via Solid Freeform Fabrication

PubMed Central

Liao, Han-Tsung; Jiang, Cho-Pei

2014-01-01

The study described a novel bone tissue scaffold fabricated by computer-aided, air pressure-aided deposition system to control the macro- and microstructure precisely. The porcine bone marrow stem cells (PBMSCs) seeded on either mPEG-PCL-mPEG (PCL) or mPEG-PCL-mPEG/hydroxyapatite (PCL/HA) composite scaffold were cultured under osteogenic medium to test the ability of osteogenesis in vitro. The experimental outcomes indicated that both scaffolds possessed adequate pore size, porosity, and hydrophilicity for the attachment and proliferation of PBMSCs and the PBMSCs expressed upregulated genes of osteogensis and angiogenesis in similar manner on both scaffolds. The major differences between these two types of the scaffolds were the addition of HA leading to higher hardness of PCL/HA scaffold, cell proliferation, and VEGF gene expression in PCL/HA scaffold. However, the in vivo bone forming efficacy between PBMSCs seeded PCL and PCL/HA scaffold was different from the in vitro results. The outcome indicated that the PCL/HA scaffold which had bone-mimetic environment due to the addition of HA resulted in better bone regeneration and mechanical strength than those of PCL scaffold. Therefore, providing a bone-mimetic scaffold is another crucial factor for bone tissue engineering in addition to the biocompatibility, 3D architecture with high porosity, and interpored connection. PMID:24868523

Graphene oxide stabilized by PLA-PEG copolymers for the controlled delivery of paclitaxel.

PubMed

Angelopoulou, A; Voulgari, E; Diamanti, E K; Gournis, D; Avgoustakis, K

2015-06-01

To investigate the application of water-dispersible poly(lactide)-poly(ethylene glycol) (PLA-PEG) copolymers for the stabilization of graphene oxide (GO) aqueous dispersions and the feasibility of using the PLA-PEG stabilized GO as a delivery system for the potent anticancer agent paclitaxel. A modified Staudenmaier method was applied to synthesize graphene oxide (GO). Diblock PLA-PEG copolymers were synthesized by ring-opening polymerization of dl-lactide in the presence of monomethoxy-poly(ethylene glycol) (mPEG). Probe sonication in the presence of PLA-PEG copolymers was applied in order to reduce the hydrodynamic diameter of GO to the nano-size range according to dynamic light scattering (DLS) and obtain nano-graphene oxide (NGO) composites with PLA-PEG. The composites were characterized by atomic force microscopy (AFM), thermogravimetric analysis (TGA), and DLS. The colloidal stability of the composites was evaluated by recording the size of the composite particles with time and the resistance of composites to aggregation induced by increasing concentrations of NaCl. The composites were loaded with paclitaxel and the in vitro release profile was determined. The cytotoxicity of composites against A549 human lung cancer cells in culture was evaluated by flow cytometry. The uptake of FITC-labeled NGO/PLA-PEG by A549 cells was also estimated with flow cytometry and visualized with fluorescence microscopy. The average hydrodynamic diameter of NGO/PLA-PEG according to DLS ranged between 455 and 534 nm, depending on the molecular weight and proportion of PLA-PEG in the composites. NGO/PLA-PEG exhibited high colloidal stability on storage and in the presence of high concentrations of NaCl (far exceeding physiological concentrations). Paclitaxel was effectively loaded in the composites and released by a highly sustained fashion. Drug release could be regulated by the molecular weight of the PLA-PEG copolymer and its proportion in the composite. The paclitaxel

Application of microchip CGE for the analysis of PEG-modified recombinant human granulocyte-colony stimulating factors.

PubMed

Park, Eun Ji; Lee, Kyung Soo; Lee, Kang Choon; Na, Dong Hee

2010-11-01

The purpose of this study was to evaluate the microchip CGE (MCGE) for the analysis of PEG-modified granulocyte-colony stimulating factor (PEG-G-CSF) prepared with PEG-aldehydes. The unmodified and PEG-modified G-CSFs were analyzed by Protein 80 and 230 Labchips on the Agilent 2100 Bioanalyzer. The MCGE allowed size-based separation and quantitation of PEG-G-CSF. The Protein 80 Labchip was useful for PEG-5K-G-CSF, while the Protein 230 Labchip was more suitable for PEG-20K-G-CSF. The MCGE was also used to monitor a search for optimal PEG-modification (PEGylation) conditions to produce mono-PEG-G-CSF. This study demonstrates the usefulness of MCGE for monitoring and optimizing the PEGylation of G-CSF with the advantages of speed, minimal sample consumption, and automatic quantitation.

Conditional internalization of PEGylated nanomedicines by PEG engagers for triple negative breast cancer therapy

NASA Astrophysics Data System (ADS)

Su, Yu-Cheng; Burnouf, Pierre-Alain; Chuang, Kuo-Hsiang; Chen, Bing-Mae; Cheng, Tian-Lu; Roffler, Steve R.

2017-06-01

Triple-negative breast cancer (TNBC) lacks effective treatment options due to the absence of traditional therapeutic targets. The epidermal growth factor receptor (EGFR) has emerged as a promising target for TNBC therapy because it is overexpressed in about 50% of TNBC patients. Here we describe a PEG engager that simultaneously binds polyethylene glycol and EGFR to deliver PEGylated nanomedicines to EGFR+ TNBC. The PEG engager displays conditional internalization by remaining on the surface of TNBC cells until contact with PEGylated nanocarriers triggers rapid engulfment of nanocargos. PEG engager enhances the anti-proliferative activity of PEG-liposomal doxorubicin to EGFR+ TNBC cells by up to 100-fold with potency dependent on EGFR expression levels. The PEG engager significantly increases retention of fluorescent PEG probes and enhances the antitumour activity of PEGylated liposomal doxorubicin in human TNBC xenografts. PEG engagers with specificity for EGFR are promising for improved treatment of EGFR+ TNBC patients.

Control of silk microsphere formation using polyethylene glycol (PEG).

PubMed

Wu, Jianbing; Zheng, Zhaozhu; Li, Gang; Kaplan, David L; Wang, Xiaoqin

2016-07-15

A one step, rapid method to prepare silk microspheres was developed, with particle size controlled by the addition of polyethylene glycol (PEG). PEG molecular weight (4.0K-20.0KDa) and concentration (20-50wt%), as well as silk concentration (5-20wt%), were key factors that determined particle sizes varying in a range of 1-100μm. Addition of methanol to the PEG-silk combinations increased the content of crystalline β-sheet in the silk microspheres. To track the distribution and degradation of silk microspheres in vivo, 3-mercaptopropionic acid (MPA)-coated CdTe quantum dots (QDs) were physically entrapped in the silk microspheres. QDs tightly bound to the β-sheet domains of silk via hydrophobic interactions, with over 96% of the loaded QDs remaining in the silk microspheres after exhaustive extraction. The fluorescence of QDs-incorporated silk microspheres less stable in cell culture medium than in phosphate buffer solution (PBS) and water. After subcutaneous injection in mice, microspheres prepared from 20% silk (approx. 30μm diameter particles) still fluoresced at 24h, while those prepared from 8% silk (approx. 4μm diameter particles) and free QDs were not detectable, reflecting the QDs quenching and particle size effect on microsphere clearance in vivo. The larger microspheres were more resistant to cell internalization and degradation. Since PEG is an FDA-approved polymer, and silk is FDA approved for some medical devices, the methods developed in the present study will be useful in a variety of biomedical applications where simple, rapid and scalable preparation of silk microspheres is required. The work is of significance to the biomaterial and controlled release society because it provides a new option for fabricating silk microspheres in one simple step of mixing silk and polyethylene glycol (PEG), with the size and properties of microspheres controllable by PEG molecular weight as well as PEG and silk concentrations. Although fabrication of silk

Generation, characterization and in vivo biological activity of two distinct monoclonal anti-PEG IgMs

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

Hashimoto, Yosuke; Shimizu, Taro; Mima, Yu

PEGylation, the attachment of polyethylene glycol (PEG) to nanocarriers and proteins, is a widely accepted approach to improving the in vivo efficacy of the non-PEGylated products. However, both PEGylated liposomes and PEGylated proteins reportedly trigger the production of specific antibodies, mainly IgM, against the PEG moiety, which possibly leads to a reduction in safety and therapeutic efficacy of the PEGylated products. In the present study, two monoclonal anti-PEG IgMs — HIK-M09 via immunization with an intravenous injection of PEGylated liposomes (SLs) and HIK-M11 via immunization with a subcutaneous administration of PEGylated ovalbumin (PEG-OVA) were successfully generated. The generated IgMs showedmore » efficient reactivity to mPEG{sub 2000} conjugated to 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine (DSPE), PEGylated liposome (SL) and PEG-OVA. It appears that HIK-M09 recognizes ethoxy (OCH{sub 2}CH{sub 2}) repeat units along with a terminal motif of PEG, while HIK-M11 recognizes only ethoxy repeat units of PEG. Such unique properties allow HIK-M09 to bind with dense PEG. In addition, their impact on the in vivo clearance of the PEGylated products was investigated. It was found that the generated ant-PEG IgMs induced a clearance of SL as they were intravenously administered with SL. Interestingly, the HIK-M11, generated by PEG-OVA, induced the clearance of both SL and PEG-OVA, while the HIK-M09, generated by SL, induced the clearance of SL only. We here revealed that the presence of serum anti-PEG IgM and the subsequent binding of anti-PEG IgM to the PEGylated products are not necessarily related to the enhanced clearance of the products. It appears that subsequent complement activation following anti-PEG IgM binding is the most important step in dictating the in vivo fate of PEGylated products. This study may have implications for the design, development and clinical application of PEGylated products and therapeutics. - Highlights: • Two

Efficacy of polyethylene glycol 4000 on constipation of posttraumatic bedridden patients.

PubMed

Zhang, Lian-yang; Yao, Yuan-zhang; Wang, Tao; Fei, Jun; Shen, Yue; Chen, Yong-hua; Zong, Zhao-wen

2010-06-01

To investigate the efficacy and safety of polyethylene glycol 4000 on adult patients with functional constipation due to posttraumatic confinement to bed. A total of 201 posttraumatic bedridden patients were studied in this prospective, open-labeled, single-group study. Polyethylene glycol 4000 was administered orally for 14 days and the dosage was adjusted according to the Bristol stool types. Demographic characteristics, disease status, treatment period and factors affecting clinical outcome, especially the concomitant medications, were recorded. After administration of polyethylene glycol 4000, 194 cases (96.52%) showed remission of constipation, including 153 (76.12%) persistent remission. The average defecation frequency increased significantly after treatment and the percentage of patients with stools of normal types (Bristol types 3-5) increased as well. Genders, ages and concomitant medications showed no significant influence on the persistent remission rate. After consecutive treatment for two weeks, patients with slight movement showed a significantly higher remission rate than those without movement (95% vs 80%). At the end of treatment, most accompanying symptoms were relieved obviously. Patients with a medical history of constipation or ever taking laxatives showed a lower remission rate. Sixty cases (29.85%) developed diarrhea during the observational period, among whom 6 (10%) withdrew from the clinical observation voluntarily at the first onset of diarrhea. Two cases suffered from abdominal pain. Polyethylene glycol 4000 has efficacy on functional constipation in posttraumatic bedridden patients. Furthermore, patients with milder symptoms, more movement in bed, and longer duration of treatment but without accompanying symptoms can achieve a higher remission rate.

Development and in vivo evaluation of an oral insulin-PEG delivery system.

PubMed

Calceti, P; Salmaso, S; Walker, G; Bernkop-Schnürch, A

2004-07-01

Insulin-monomethoxypoly(ethylene glycol) derivatives were obtained by preparation of mono- and di-terbutyl carbonate insulin derivatives, reaction of available protein amino groups with activated 750 Da PEG and, finally, amino group de-protection. This procedure allowed for obtaining high yield of insulin-1PEG and insulin-2PEG. In vivo studies carried out by subcutaneous injection into diabetic mice demonstrated that the two bioconjugates maintained the native biological activity. In vitro, PEGylation was found to enhance the hormone stability towards proteases. After 1 h incubation with elastase, native insulin, insulin-1PEG and insulin-2PEG undergo about 70, 30 and 10% degradation, respectively, while in the presence of pepsin protein degradation was 100, 70 and 50%, respectively. The attachment of low molecular weight PEG did not significantly (P >0.05) alter insulin permeation behavior across the intestinal mucosa. Insulin-1PEG was formulated into mucoadhesive tablets constituted by the thiolated polymer poly(acrylic acid)-cysteine. The therapeutic agent was sustained released from these tablets within 5 h. In vivo, by oral administration to diabetic mice, the glucose levels were found to decrease of about 40% since the third hour from administration and the biological activity was maintained up to 30 h. According to these results, the combination of PEGylated insulin with a thiolated polymer used as drug carrier matrix might be a promising strategy for oral insulin administration.

PEG-rHuMGDF ameliorates thrombocytopenia in carboplatin-treated rats without inducing myelofibrosis.

PubMed

Ide, Y; Harada, K; Imai, A; Yanagida, M

1999-08-01

We examined the effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on carboplatin-induced thrombocytopenia in rats. The focus was on whether myelofibrosis is associated with the PEG-rHuMGDF treatment in this chemotherapy model. After a single injection of carboplatin, rats received subcutaneous PEG-rHuMGDF at pharmacologic doses (1,3, or 30 micrograms/kg) or a vehicle daily for 7 days. PEG-rHuMGDF at more than 3 micrograms/kg ameliorated the thrombocytopenia at day 10. Histologically, no myelofibrosis was detected in the rats treated with PEG-rHuMGDF or vehicle. Subsequently, PEG-rHuMGDF at a suprapharmacologic dose (100 micrograms/kg) was subcutaneously administered to normal and to carboplatin-treated rats daily for 7 days. Histological analysis revealed that the treatment with PEG-rHuMGDF induced myelofibrosis in the normal rats but not in the carboplatin-treated rats. Additionally, the transforming growth factor-beta 1 (TGF-beta 1) levels in the extracellular fluid and the whole extract of the bone marrow were increased to a much lesser degree in the carboplatin-treated rats compared to the normal rats. These findings suggest that PEG-rHuMGDF is effective for carboplatin-induced thrombocytopenia. Proper control of platelet counts and TGF-beta 1 levels is essential so that myelofibrosis is not induced in clinical use.

47 CFR 32.4000 - Current accounts and notes payable.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Section 32.4000 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES... to others for recurring trade obligations, and not provided for in other accounts, such as those for traffic settlements, material and supplies, repairs to telecommunications plant, matured rents, and...

Glutathione-mediated release of Bodipy® from PEG cofunctionalized gold nanoparticles

PubMed Central

Kumar, Dhiraj; Meenan, Brian J; Dixon, Dorian

2012-01-01

Gold nanoparticles synthesized via sodium citrate reduction of chloroauric acid (HAuCl4) were functionalized with either various concentrations of thiol-terminated Bodipy® FL L-cystine (0.5, 1.0, 1.5, and 2.0 μg/mL) or Bodipy-poly(ethylene glycol) at concentrations of 0.5–18.75, 1.0–12.50, and 1.5–6.25 μg/mL to form a mixed monolayer of BODIPY-PEG. Thiol-terminated Bodipy, a fluorescing molecule, was used as the model drug, while PEG is widely used in drug-delivery applications to shield nanoparticles from unwanted immune responses. Understanding the influence of PEG-capping on payload release is critical because it is the most widely used type of nanoparticle functionalization in drug delivery studies. It has been previously reported that glutathione can trigger release of thiol-bound payloads from gold nanoparticles. Bodipy release from Bodipy capped and from Bodipy-PEG functionalized gold nanoparticles was studied at typical intracellular glutathione levels. It was observed that the addition of PEG capping inhibits the initial burst release observed in gold nanoparticles functionalized only with Bodipy and inhibits nanoparticle aggregation. Efficient and controlled payload release was observed in gold nanoparticles cofunctionalized with only a limited amount of PEG, thus enabling the coattachment of large amounts of drug, targeting groups or other payloads. PMID:22915847

PEG 3350 Administration Is Not Associated with Sustained Elevation of Glycol Levels.

PubMed

Williams, Kent C; Rogers, Lynette K; Hill, Ivor; Barnard, John; Di Lorenzo, Carlo

2018-04-01

To determine whether trace amounts of ethylene glycol (EG), diethylene glycol (DEG), or triethylene glycol (TEG) in PEG 3350 are associated with increased blood levels of EG, DEG, or TEG in children receiving daily PEG 3350 therapy. Blood samples were drawn from 9 children who were being treated for constipation with PEG 3350 (6-12 years old) before and every 30 minutes for 3 hours after receiving 17 g of PEG 3350. PEG 3350, tap water, and blood samples from 18 age- and sex-matched controls also were analyzed. Baseline blood levels of EG and TEG did not differ between control and treated groups. DEG levels (median [IQR]) were lower in the PEG 3350 group (40.13 ng/mL [36.69, 63.94] vs 92.83 ng/mL [51.06, 128.93], P = .008). After PEG 3350 dose, levels of EG (390.51 ng/mL [326.06, 624.55]) and TEG (2.21 ng/mL [0, 4.5]) peaked at 90 minutes at 1032.81 ng/mL (826.84, 1486.13) (P = .009) and 35.17 ng/mL (15.81, 45.13) (P = .0005), respectively. DEG levels did not significantly change. Standard 17-g doses of PEG 3350 in 8 oz (237 mL) of water resulted in concentrations (mean ± SD) of EG, DEG, and TEG of 1.32 ± 0.23 µg/mL, 0.18 ± 0.03 µg/mL, and 0.12 ± 0.01 µg/mL, respectively. EG, DEG, and TEG levels in public water supply were 0.07 µg/mL, 0.21 µg/mL, and 0.02 µg/mL, respectively. Daily PEG 3350 therapy in children was not associated with sustained elevation of EG, DEG, or TEG blood levels over levels in matched controls. Although EG and TEG levels increased after a standard dose of PEG 3350, their peak values remained well below toxic levels. Copyright © 2017 Elsevier Inc. All rights reserved.

Gravity-regulated formation of the peg in developing cucumber seedlings

NASA Technical Reports Server (NTRS)

Takahashi, H.; Scott, T. K.

1994-01-01

It has been proposed that peg formation in the vascular transition region (TR zone) between the hypocotyl and the root in Cucurbitaceae seedlings is a gravimorphogenetic phenomenon. Initiation of the peg became visible 36 h after imbibition when cucumber (Cucumis sativus L. cv. Burpee Hybrid II) seeds were germinated in a horizontal position at 24 degrees C in the dark. Simultaneously, sedimented amyloplasts (putative statoliths) were apparent in the sheath cells surrounding the vascular strands, and in the cortical cells immediately adjacent to them, in the TR zone. In contrast, the other cortical cells, some of which were destined to develop into the peg, contained amyloplasts which were not sedimented. These results suggest that the graviperception mechanism for peg formation may be like that of statoliths in shoot gravitropism. By 48 h following imbibition, the cells of the TR zone still had sedimented amyloplasts but had lost their sensitivity to gravity, possibly because of their maturation.

Analysis of peg formation in cucumber seedlings grown on clinostats and in a microgravity (space) environment.

PubMed

Link, B M; Cosgrove, D J

1999-12-01

In young cucumber seedlings, the peg is a polar out-growth of tissue that functions by snagging the seed coat, thereby freeing the cotyledons. Previous studies have indicated that peg formation is gravity dependent. In this study we analyzed peg formation in cucumber seedlings (Cucumis sativus L. cv Burpee Hybrid II) grown under conditions of normal gravity, microgravity, and simulated microgravity (clinostat rotation). Seeds were germinated on the ground, in clinostats and on board the space shuttle (STS 95) for 1-2 days, frozen and subsequently examined for their stage of development, degree of hook formation, number of pegs formed, and peg morphology. The frequency of peg formation in space grown seedlings was found to be nearly identical to that of clinostat grown seedlings and to differ from that of seedlings germinated under normal gravity only in a minority of cases; approximately 6% of the seedlings formed two pegs and nearly 2% of the seedlings lacked pegs, whereas such abnormalities did not occur in ground controls. The degree of hook formation was found to be less pronounced for space grown seedlings, compared to clinostat grown seedlings, indicating a greater degree of decoupling between peg formation and hook formation in space. Nonetheless, in all seedlings having single pegs and a hook, the peg was found to be positioned correctly on the inside of the hook, showing that there is coordinate development even in microgravity environments. Peg morphologies were altered in space grown samples, with the pegs having a blunt appearance and many pegs showing alterations in expansion, with the peg extending out over the edges of the seed coat and downwards. These phenotypes were not observed in clinostat or ground grown seedlings.

Analysis of peg formation in cucumber seedlings grown on clinostats and in a microgravity (space) environment

NASA Technical Reports Server (NTRS)

Link, B. M.; Cosgrove, D. J.

1999-01-01

In young cucumber seedlings, the peg is a polar out-growth of tissue that functions by snagging the seed coat, thereby freeing the cotyledons. Previous studies have indicated that peg formation is gravity dependent. In this study we analyzed peg formation in cucumber seedlings (Cucumis sativus L. cv Burpee Hybrid II) grown under conditions of normal gravity, microgravity, and simulated microgravity (clinostat rotation). Seeds were germinated on the ground, in clinostats and on board the space shuttle (STS 95) for 1-2 days, frozen and subsequently examined for their stage of development, degree of hook formation, number of pegs formed, and peg morphology. The frequency of peg formation in space grown seedlings was found to be nearly identical to that of clinostat grown seedlings and to differ from that of seedlings germinated under normal gravity only in a minority of cases; approximately 6% of the seedlings formed two pegs and nearly 2% of the seedlings lacked pegs, whereas such abnormalities did not occur in ground controls. The degree of hook formation was found to be less pronounced for space grown seedlings, compared to clinostat grown seedlings, indicating a greater degree of decoupling between peg formation and hook formation in space. Nonetheless, in all seedlings having single pegs and a hook, the peg was found to be positioned correctly on the inside of the hook, showing that there is coordinate development even in microgravity environments. Peg morphologies were altered in space grown samples, with the pegs having a blunt appearance and many pegs showing alterations in expansion, with the peg extending out over the edges of the seed coat and downwards. These phenotypes were not observed in clinostat or ground grown seedlings.

Preparation of monodisperse PEG hydrogel composite microspheres via microfluidic chip with rounded channels

NASA Astrophysics Data System (ADS)

Yu, Bing; Cong, Hailin; Liu, Xuesong; Ren, Yumin; Wang, Jilei; Zhang, Lixin; Tang, Jianguo; Ma, Yurong; Akasaka, Takeshi

2013-09-01

An effective microfluidic method to fabricate monodisperse polyethylene glycol (PEG) hydrogel composite microspheres with tunable dimensions and properties is reported in this paper. A T-junction microfluidic chip equipped with rounded channels and online photopolymerization system is applied for the microsphere microfabrication. The shape and size of the microspheres are well controlled by the rounded channels and PEG prepolymer/silicon oil flow rate ratios. The obtained PEG/aspirin composite microspheres exhibit a sustained release of aspirin for a wide time range; the obtained PEG/Fe3O4 nanocomposite microspheres exhibit excellent magnetic properties; and the obtained binary PEG/dye composite microspheres show the ability to synchronously load two functional components in the same peanut-shaped or Janus hydrogel particles.

Sensitive and rapid detection of anti-PEG in blood using surface plasmon resonance sensor (Conference Presentation)

NASA Astrophysics Data System (ADS)

Sun, Fang; Jiang, Shaoyi; Yu, Qiuming

2016-03-01

Polyethylene glycol (PEG) is widely used to modify many therapeutic proteins and nanoparticles to reduce their immunogenicity and to improve their pharmacokinetic and therapeutic properties. It is generally accepted that PEG is non-immunogenic and non-antigenic. However, an emerging of literature and studies shows that the immune system can generate specific antibodies binding PEG. These anti-PEG antibodies not only correlate with adverse reactions appeared after patient infusions, but are also found to be the reason for therapeutic efficacy loss during chronical administrations. In addition, because of constant exposure to PEG in daily consumer products including detergents, processed food and cosmetics, a substantial proportion of the population has likely developed anti-PEG immunity. Thus a method to quickly and accurately measure the anti-PEG antibody level is desired. Nevertheless, the gold standard to detect anti-PEG antibodies is ELISA, which is costly and time-consuming especially for quantification. Herein, we demonstrated the anti-PEG measurement in blood serum using surface plasmon resonance (SPR) sensor. Several PEG-based surface functionalization on SPR sensor chip were studied in terms of protein resistance and the limit of detection (LOD) of anti-PEG. The quantitative detection can be achieved in less than 30 min with LOD comparable to ELISA. Furthermore, the IgG and IgM of anti-PEG can be differentiated by following the secondary antibody.

Enhanced circulation half-life of site-specific PEGylated rhG-CSF: optimization of PEG molecular weight.

PubMed

Zhai, Yanqin; Zhao, Yongjiang; Lei, Jiandu; Su, Zhiguo; Ma, Guanghui

2009-07-15

Recombinant human granulocyte colony stimulating factor (rhG-CSF) and its PEGylated product "mono-PEG20-GCSF" have already been widely used for treatment of all kinds of neutropenia. However, the high required dosage of mono-PEG20-GCSF made it relatively expensive in clinical use. We postulated that an N-terminal site-specific PEGylated rhG-CSF with higher PEG Mw (PEG30 kDa) might be able to achieve longer circulation half-life while retaining its bioactivity, allowing the reduction of dosage for clinical use. rhG-CSF was PEGylated at the N-terminus by 5 kDa, 10 kDa, 20 kDa and 30 kDa methoxy-poly(ethylene glycol)-propionaldehyde (mPEG-ALD), and the four PEGylates were compared with respect to reaction, separation, characterization and also in vivo/in vitro activity, results showed that the mPEG-ALD of higher Mw demonstrated better N-terminal site-specific selectivity, separation purity and yield. The production cost and in vitro activity of mono-PEG30-GCSF and mono-PEG20-GCSF were almost the same, while mono-PEG30-GCSF showed longer in vivo circulation half-life and 60% higher drug bioavailability than mono-PEG20-GCSF. Consequently, mono-PEG30-GCSF shall be administered at a lower dosage than mono-PEG20-GCSF while retaining the same therapeutic efficacy.

Inhibition of HeLa cell growth by doxorubicin-loaded and tuftsin-conjugated arginate-PEG microparticles.

PubMed

Hu, Tianmu; Qahtan, Anwar Saeed Ahmed; Lei, Lei; Lei, Zhixin; Zhao, Dapeng; Nie, Hemin

2018-03-01

In order to improve the release pattern of chemotherapy drug and reduce the possibility of drug resistance, poly(ethylene glycol amine) (PEG)-modified alginate microparticles (ALG-PEG MPs) were developed then two different mechanisms were employed to load doxorubicin (Dox): 1) forming Dox/ALG-PEG complex by electrostatic attractions between unsaturated functional groups in Dox and ALG-PEG; 2) forming Dox-ALG-PEG complex through EDC-reaction between the amino and carboxyl groups in Dox and ALG, respectively. Additionally, tuftsin (TFT), a natural immunomodulation peptide, was conjugated to MPs in order to enhance the efficiency of cellular uptake. It was found that the Dox-ALG-PEG-TFT MPs exhibited a significantly slower release of Dox than Dox/ALG-PEG-TFT MPs in neutral medium, suggesting the role of covalent bonding in prolonging Dox retention. Besides, the release of Dox from these MPs was pH-sensitive, and the release rate was observably increased at pH 6.5 compared to the case at pH 7.4. Compared with Dox/ALG-PEG MPs and Dox-ALG-PEG MPs, their counterparts further conjugated with TFT more efficiently inhibited the growth of HeLa cells over a period of 48 h, implying the effectiveness of TFT in enhancing cellular uptake of MPs. Over a period of 48 h, Dox-ALG-PEG-TFT MPs inhibited the growth of HeLa cells less efficiently than Dox/ALG-PEG-TFT MPs but the difference was not significant ( p  > 0.05). In consideration of the prolonged and sustained release of Dox, Dox-ALG-PEG-TFT MPs possess the advantages for long-term treatment.

76 FR 68660 - Airworthiness Directives; Pratt & Whitney Division (PW) PW4000 Series Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-07

... Airworthiness Directives; Pratt & Whitney Division (PW) PW4000 Series Turbofan Engines AGENCY: Federal Aviation... airworthiness directive (AD) for PW4000 series turbofan engines. This proposed AD would require replacing the..., PW4152, PW4156, PW4156A, PW4158, PW4160, PW4460, PW4462, and PW4650 turbofan engines, including models...

Acute toxicity and pharmacokinetics of 13 nm-sized PEG-coated gold nanoparticles

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

Cho, Wan-Seob; Cho, Minjung; Jeong, Jinyoung

2009-04-01

In general, gold nanoparticles are recognized as being as nontoxic. Still, there have been some reports on their toxicity, which has been shown to depend on the physical dimension, surface chemistry, and shape of the nanoparticles. In this study, we carry out an in vivo toxicity study using 13 nm-sized gold nanoparticles coated with PEG (MW 5000). In our findings the 13 nm sized PEG-coated gold nanoparticles were seen to induce acute inflammation and apoptosis in the liver. These nanoparticles were found to accumulate in the liver and spleen for up to 7 days after injection and to have longmore » blood circulation times. In addition, transmission electron microscopy showed that numerous cytoplasmic vesicles and lysosomes of liver Kupffer cells and spleen macrophages contained the PEG-coated gold nanoparticles. These findings of toxicity and kinetics of PEG-coated gold nanoparticles may have important clinical implications regarding the safety issue as PEG-coated gold nanoparticles are widely used in biomedical applications.« less

Peg supported thermal insulation panel

DOEpatents

Nowobilski, Jeffert J.; Owens, William J.

1985-01-01

A thermal insulation panel which is lightweight, load bearing, accommodates thermal stress, and has excellent high temperature insulation capability comprising high performance insulation between thin metal walls supported by high density, high strength glass pegs made in compliance with specified conditions of time, temperature and pressure.

True incidence and clinical significance of pneumoperitoneum after PEG placement: a prospective study.

PubMed

Wiesen, Ari J; Sideridis, Kostas; Fernandes, Angelo; Hines, Jonathan; Indaram, Anant; Weinstein, Lenny; Davidoff, Samuel; Bank, Simmy

2006-12-01

PEG is a widely used method for providing nutritional support. Although pneumoperitoneum is a known finding after PEG placement, its true incidence is subject to debate. Small retrospective studies have found varied rates of free air after PEG placement. There were a total of 65 patients. To assess the true incidence of pneumoperitoneum and its clinical significance. Prospective study. Long Island Jewish Medical Center. We obtained upright and anterior-posterior chest radiographs of 65 patients within 3 hours after PEG placement. Type of PEG tube, gauge of the needle used, number of sticks, and indications were recorded. The presence of pneumoperitoneum on the initial chest film was considered to be a positive finding. After a positive result, a repeat chest film was obtained 72 hours later to determine whether there was progression or resolution of the free air. Patients enrolled in the study were also monitored clinically for evidence of peritonitis. Of the 65 patients who underwent PEG placement, 13 developed a pneumoperitoneum on the initial chest radiograph; there was complete resolution of pneumoperitoneum at 72 hours in 10 of the 13 patients. In 3 patients, the free air persisted but was of no clinical significance. The free air was quantified by measuring the height of the air column under the diaphragm and was graded with a scoring system (0, no air; 1, small; 2, moderate; 3, large). Eleven patients who underwent PEG died during the hospitalization; none of the deaths were related to the PEG placement or pneumoperitoneum. The other 54 patients were discharged to a skilled nursing facility. No patients in the study had clinical evidence of peritonitis. There were no adverse events, ie, infection or bleeding, associated with the PEG placement in any of the patients. Our data suggest that pneumoperitoneum after PEG placement is common and, in the absence of clinical symptoms, is of no clinical significance and does not warrant any further intervention.

Bio-orthogonal coupling on PEG-modified quantum dots (Conference Presentation)

NASA Astrophysics Data System (ADS)

Zhan, Naiqian; Palui, Goutam; Mattoussi, Hedi

2017-02-01

We have designed two sets of aldehyde- and azide-modified ligands; these ligands also present lipoic acid anchors and PEG hydrophilic moieties (LA-PEG-CHO and LA-PEG-azide). We combined this design with a photoligation strategy to prepare QDs with good control over the fraction of intact reactive groups per nanocrystal. We first applied the extremely efficient hydrazone coupling ligation to react the QD with hydrozinopyridine, which produces a well-defined absorption feature at 354 nm ascribed to the hydrazone chromophore. We exploited this signature to measure the number of aldehyde groups per QD when the fraction of LA-PEG-CHO per nanocrystal was varied, by comparing the optical signature at 354 with the molar extinction coefficient of the chromophore. This allowed us to extract an estimate for the number of LA-PEG ligand per QDs for a few distinct size nanocrystals. We further complemented these findings with the use of NMR spectroscopy to estimate of the ligand density using well defined signatures of the terminal protons of the ligands, and found a good agreement between the two techniques. We then showed that bio-orthogonal reactions based on CLICK and hydrazone coupling can be achieved using QDs presenting a mixture of azide and CHO functions. We anticipate that this strategy could be applied other nanoparticles such as those of Au and metals and semiconductor nanocrystals.

Asymmetrical flow field-flow fractionation for the analysis of PEG-asparaginase.

PubMed

John, C; Herz, T; Boos, J; Langer, K; Hempel, G

2016-01-01

Monomethoxypolyethylene glycol L-asparaginase (PEG-ASNASE) is the PEGylated version of the enzyme L-asparaginase (ASNASE). Both are used for remission induction in acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). The treatment control is generally carried out by performing activity assays, though methods to determine the actual enzyme rather than its activity are rare. Using asymmetrical flow field-flow fractionation (AF4) offered the chance to develop a method capable of simultaneously measuring PEG-ASNASE and PEG. A method validation was performed in accordance with FDA guidelines for PEG-ASNASE from non-biological solutions. The method unfolded a linearity of 15-750 U/mL with coefficients of correlation of r(2)>0.99. The coefficients of variation (CV) for within-run and between-run variability were 1.18-10.15% and 2.43-8.73%, respectively. Furthermore, the method was used to perform stability tests of the product Oncaspar® (PEG-ASNASE) and estimation of the molecular weight by multi-angle light scattering (MALS) of stressed samples to correlate them with the corresponding activity. The findings indicate that Oncaspar® stock solution should not be stored any longer than 24 h at room temperature and cannot be frozen in pure aqueous media. The validated method might be useful for the pharmaceutical industry and its quality control of PEG-ASNASE production. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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

2016-06-01

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

Crosslinking of SAVY-4000 O-rings as a Function of Aging Conditions

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

Van Buskirk, Caleb Griffith

SAVY-4000 containers were developed as a part of DOE M 441.1-1 to protect workers who handle stored nuclear material from exposure due to loss of containment.1 The SAVY-4000 is comprised of three parts: a lid, a container, and a cross-linked fluoropolymer O-ring. Degradation of the O-ring during use could limit the lifetime of the SAVY-4000. In order to quantify the chemical changes of the Oring over time, the molecular weight between crosslinks was determined as a function of aging conditions using a swelling technique. Because the O-ring is a cross-linked polymer, it will absorb solvent into its matrix without dissolving.more » The relative amount of solvent uptake can be related to the degree of crosslinking using an equation developed by Paul Flory and John Rehner Jr3. This method was used to analyze O-ring samples aged under thermal and ionizing-radiation conditions. It was found that at the harsher thermal gaining conditions in absence of ionizing-radiation the average molecular weight between crosslinks decreased, indicating a rise in crosslinks, which may be attributable to advanced aging with no ionizing radiation present. Inversely, in the presence of ionizing radiation it was found that material has a higher level of cross-linking with age. This information could be used to help predict the lifetime of the O-rings in SAVY-4000 containers under service conditions.« less

Peg supported thermal insulation panel

DOEpatents

Nowobilski, J.J.; Owens, W.J.

1985-04-30

A thermal insulation panel which is lightweight, load bearing, accommodates thermal stress, and has excellent high temperature insulation capability comprises high performance insulation between thin metal walls supported by high density, high strength glass pegs made in compliance with specified conditions of time, temperature and pressure. 2 figs.

Ultrasound enhances in vivo tumor expression of plasmid DNA by PEG-introduced cationized dextran.

PubMed

Hosseinkhani, Hossein; Tabata, Yasuhiko

2005-11-28

This study is an investigation to experimentally confirm whether or not ultrasound (US) irradiation is effective in enhancing the in vivo gene expression of plasmid DNA in tumor. Dextran was cationized by introducing spermine to the hydroxyl groups to allow to polyionically complex with a plasmid DNA. The cationized dextran prepared was additionally modified with poly(ethylene glycol) (PEG) molecules which have an active ester and methoxy groups at each terminal, to obtain cationized dextran with different percentages of PEG introduced. Various cationized dextrans with or without PEG introduction were mixed with a plasmid DNA of LacZ to form cationized dextran-plasmid DNA complexes. Electrophoretical examination revealed that the plasmid DNA was complexed both with the cationized dextran and PEG-introduced cationized dextran, irrespective of the PEG introduction percentage, although the higher N/P ratio was needed for plasmid DNA complexation with the latter. By complexation with the cationized dextran, the zeta potential of plasmid DNA was changed to be positive. The charge of PEG-introduced cationized dextran-plasmid DNA complexes became close to 0 mV as their percentage of PEG introduced increased, although the molecular size was about 250 nm, irrespective of the PEG introduction. When cationized dextran-plasmid DNA complexes with or without PEG introduction were intravenously injected to mice carrying a subcutaneous Meth-AR-1 fibrosarcoma mass and the subsequent US irradiation to the tumor mass percutaneously, the PEG-introduced cationized dextran-plasmid DNA complex plus US irradiation enhanced the tumor level of gene expression to a significantly high extent compared with the cationized dextran-plasmid DNA complex and free plasmid DNA with or without US irradiation. The enhanced level depended on the time period and timing of US irradiation. Fluorescent microscopic studies revealed that the localization of plasmid DNA and the gene expression were observed in

Randomised clinical trial: low-volume bowel preparation for colonoscopy - a comparison between two different PEG-based formulations.

PubMed

Repici, A; Cestari, R; Annese, V; Biscaglia, G; Vitetta, E; Minelli, L; Trallori, G; Orselli, S; Andriulli, A; Hassan, C

2012-10-01

Low-volume bowel preparations with polyethylene glycol (PEG) have been shown to provide an equivalent cleansing with improved tolerability as compared with standard PEG bowel preparation for colonoscopy. A new iso-osmotic sulphate-free formulation of PEG-Citrate-Simethicone (PEG-CS) in combination with bisacodyl has been recently developed. To compare the quality of bowel cleansing with PEG-CS with bisacodyl vs. PEG-Ascorbate (PEG-ASC) in adult out-patients undergoing colonoscopy. Randomised, observer-blind, parallel group study in adult out-patients undergoing colonoscopy in five Italian centres. Both preparations were taken the evening before the procedure. Subjects were instructed to take 2-4 tablets of 5 mg bisacodyl at 16:00 hours and 2 L of PEG-CS at 20:00 hours or 2 L of PEG-ASC plus 1 L of additional water the day before colonoscopy. Bowel cleansing was evaluated according to the Boston Bowel Preparation Scale (≥6 scores were considered as 'clinical success'), and mucosal visibility according to a 3-point scale. Tolerability, acceptability and compliance were also evaluated. Four hundred and eight patients were randomly allocated to PEG-CS and bisacodyl (n = 204, male patient 48%, mean age 59.1 years) or PEG-ASC (n = 204, male patient 51%, age 59.4 years). In the planned per-protocol analysis, the rate of successful preparation was 79.1% following PEG-CS with bisacodyl, and 70% following PEG-ASC (P < 0.05). Mucosal visibility was evaluated as optimal in 56.1% in the PEG-CS and bisacodyl and 46.3% in the PEG-ASC group (P < 0.05). There were no serious adverse events (AE) in each of the two experimental groups. Two subjects in the PEG-ASC group discontinued the study because of AE. Polyethylene glycol-Citrate-Simethicone in combination with bisacodyl was more effective for bowel cleansing than PEG-ASC for out-patient colonoscopy. Tolerability, safety, acceptability and compliance of the two low-volume bowel preparations were similar. © 2012

Unexpected electronic perturbation effects of simple PEG environments on the optical properties of small cadmium chalcogenide clusters

NASA Astrophysics Data System (ADS)

Fukunaga, Naoto; Konishi, Katsuaki

2015-12-01

Poly(ethylene glycol) (PEG) has been widely used for the surface protection of inorganic nanoobjects because of its virtually `inert' nature, but little attention has been paid to its inherent electronic impacts on inorganic cores. Herein, we definitively show, through studies on optical properties of a series of PEG-modified Cd10Se4(SR)10 clusters, that the surrounding PEG environments can electronically affect the properties of the inorganic core. For the clusters with PEG units directly attached to an inorganic core (R = (CH2CH2O)nOCH3, 1-PEGn, n = 3, ~7, ~17, ~46), the absorption bands, associated with the low-energy transitions, continuously blue-shifted with the increasing PEG chain length. The chain length dependencies were also observed in the photoluminescence properties, particularly in the excitation spectral profiles. By combining the spectral features of several PEG17-modified clusters (2-Cm-PEG17 and 3) whose PEG and core units are separated by various alkyl chain-based spacers, it was demonstrated that sufficiently long PEG units, including PEG17 and PEG46, cause electronic perturbations in the cluster properties when they are arranged near the inorganic core. These unique effects of the long-PEG environments could be correlated with their large dipole moments, suggesting that the polarity of the proximal chemical environment is critical when affecting the electronic properties of the inorganic cluster core.Poly(ethylene glycol) (PEG) has been widely used for the surface protection of inorganic nanoobjects because of its virtually `inert' nature, but little attention has been paid to its inherent electronic impacts on inorganic cores. Herein, we definitively show, through studies on optical properties of a series of PEG-modified Cd10Se4(SR)10 clusters, that the surrounding PEG environments can electronically affect the properties of the inorganic core. For the clusters with PEG units directly attached to an inorganic core (R = (CH2CH2O)nOCH3, 1-PEGn

Dielectric studies on PEG-LTMS based polymer composites

NASA Astrophysics Data System (ADS)

Patil, Ravikumar V.; Praveen, D.; Damle, R.

2018-02-01

PEG LTMS based polymer composites were prepared and studied for dielectric constant variation with frequency and temperature as a potential candidate with better dielectric properties. Solution cast technique is used for the preparation of polymer composite with five different compositions. Samples show variation in dielectric constant with frequency and temperature. Dielectric constant is large at low frequencies and higher temperatures. Samples with larger space charges have shown larger dielectric constant. The highest dielectric constant observed was about 29244 for PEG25LTMS sample at 100Hz and 312 K.

SAVY 4000 Container Filter Design Life and Extension Implementation

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

Moore, Murray E.; Reeves, Kirk Patrick; Veirs, Douglas Kirk

The SAVY 4000 is a general purpose, reusable container for the storage of solid nuclear material inside a nuclear facility. The canister has a permitted loading for material with a thermal output not to exceed 25 watts. This wattage limit applies to all containers, regardless of their size.

Automated real time peg and tool detection for the FLS trainer box.

PubMed

Nemani, Arun; Sankaranarayanan, Ganesh

2012-01-01

This study proposes a method that effectively tracks trocar tool and peg positions in real time to allow real time assessment of the peg transfer task of the Fundamentals of Laparoscopic Surgery (FLS). By utilizing custom code along with OpenCV libraries, tool and peg positions can be accurately tracked without altering the original setup conditions of the FLS trainer box. This is achieved via a series of image filtration sequences, thresholding functions, and Haar training methods.

PPy/PMMA/PEG-based sensor for low-concentration acetone detection

NASA Astrophysics Data System (ADS)

Daneshkhah, A.; Shrestha, S.; Agarwal, M.; Varahramyan, K.

2014-05-01

A polymer pellet-based sensor device comprised of polypyrrole (PPy), polymethyl methacrylate (PMMA) and polyethylene glycol (PEG), its fabrication methods, and the experimental results for low-concentration acetone detection are presented. The design consists of a double layer pellet, where the top layer consists of PPy/PMMA and the bottom layer is composed of PPy/PMMA/PEG. Both sets of material compositions are synthesized by readily realizable chemical polymerization techniques. The mechanism of the sensor operation is based on the change in resistance of PPy and the swelling of PMMA when exposed to acetone, thereby changing the resistance of the layers. The resistances measured on the two layers, and across the pellet, are taken as the three output signals of the sensor. Because the PPy/PMMA and PPy/PMMA/PEG layers respond differently to acetone, as well as to other volatile organic compounds, it is demonstrated that the three output signals can allow the presented sensor to have a better sensitivity and selectivity than previously reported devices. Materials characterizations show formation of new composite with PPy/PMMA/PEG. Material response at various concentrations of acetone was conducted using quartz crystal microbalance (QCM). It was observed that the frequency decreased by 98 Hz for 290 ppm of acetone and by 411 Hz for 1160 ppm. Experimental results with a double layer pellet of PPy/PMMA and PPy/PMMA/PEG show an improved selectivity of acetone over ethanol. The reported acetone sensor is applicable for biomedical and other applications.

Synthesis and characterisation of PEG modified chitosan nanocapsules loaded with thymoquinone.

PubMed

Vignesh Kumar, Suresh Kumar; Renuka Devi, Ponnuswamy; Harish, Saru; Hemananthan, Eswaran

2017-02-01

Thymoquinone (TQ), a major bioactive compound of Nigella sativa seeds has several therapeutic properties. The main drawback in bringing TQ to therapeutic application is that it has poor stability and bioavailability. Hence a suitable carrier is essential for TQ delivery. Recent studies indicate biodegradable polymers are potentially good carriers of bioactive compounds. In this study, polyethylene glycol (PEG) modified chitosan (Cs) nanocapsules were developed as a carrier for TQ. Aqueous soluble low molecular weight Cs and PEG was selected among different biodegradable polymers based on their biocompatibility and efficacy as a carrier. Optimisation of synthesis of nanocapsules was done based on particle size, PDI, encapsulation efficiency and process yield. A positive zeta potential value of +48 mV, indicating good stability was observed. Scanning electron microscope and atomic-force microscopy analysis revealed spherical shaped and smooth surfaced nanocapsules with size between 100 to 300 nm. The molecular dispersion of the TQ in Cs PEG nanocapsules was studied using X-ray powder diffraction. The Fourier transform infrared spectrum of optimised nanocapsule exhibited functional groups of both polymer and drug, confirming the presence of Cs, PEG and TQ. In vitro drug release studies showed that PEG modified Cs nanocapsules loaded with TQ had a slow and sustained release.

Treatment with mPEG-SPA improves the survival of corneal grafts in rats by immune camouflage.

PubMed

Wang, Shuangyong; Li, Liangliang; Liu, Ying; Li, Chaoyang; Zhang, Min; Wang, Bowen; Huang, Zheqian; Gao, Xinbo; Wang, Zhichong

2015-03-01

We investigated the immune camouflage effects of methoxy polyethylene glycol succinimidyl propionate (mPEG-SPA) on corneal antigens and explored a novel approach for reducing corneal antigenicity, thereby decreasing corneal graft rejection. Importantly, this approach did not alter normal local immunity. Corneal grafts were treated with mPEG-SPA 5KD or 20KD (3% W/V), which could shield major histocompatibility antigen class I molecules (RT1-A) of corneal grafts. Skin grafts of Wistar rats were transplanted to SD rats. Then the splenic lymphocytes were isolated from SD rats. Subsequently, the lymphocytes were co-cultured with autologous corneal grafts or untreated corneal grafts and PEGylated grafts treated with mPEG-SPA 5KD or 20KD obtained from the counterpart skin donors, which were used as autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group, respectively. Lymphocyte proliferation was lower in mPEG-SPA 5KD group and mPEG-SPA 20KD group than in the allogeneic control. SD rats with corneal neovascularisation were used as recipients for high-risk corneal transplantation and were randomly divided into four groups: autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group. The recipients received corneal grafts from Wistar rats. Corneal graft survival was prolonged and graft rejection was reduced in the mPEG-SPA 5KD group and the mPEG-SPA 20KD group compared to the allogeneic control. Thus, we think that mPEG-SPA could immunologically camouflage corneal antigens to prolong corneal grafts survival in high-risk transplantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Impact of large aggregated uricases and PEG diol on accelerated blood clearance of PEGylated canine uricase.

PubMed

Zhang, Chun; Fan, Kai; Ma, Xuefeng; Wei, Dongzhi

2012-01-01

Uricase has proven therapeutic value in treating hyperuricemia but sufficient reduction of its immunogenicity may be the largest obstacle to its chronic use. In this study, canine uricase was modified with 5 kDa mPEG-SPA and the impact of large aggregated uricases and cross-linked conjugates induced by difunctional PEG diol on immunogenicity was investigated. Recombinant canine uricase was first expressed and purified to homogeneity. Source 15Q anion-exchange chromatography was used to separate tetrameric and aggregated uricase prior to pegylation, while DEAE anion-exchange chromatography was used to remove Di-acid PEG (precursor of PEG diol) from unfractionated 5 kDa mPEG-propionic acid. Tetrameric and aggregated uricases were separately modified with the purified mPEG-SPA. In addition, tetrameric uricases was modified with unfractionated mPEG-SPA, resulting in three types of 5 kDa mPEG-SPA modified uricase. The conjugate size was evaluated by dynamic light scattering and transmission electron microscope. The influence of differently PEGylated uricases on pharmacokinetics and immunogenicity were evaluated in vivo. The accelerated blood clearance (ABC) phenomenon previously identified for PEGylated liposomes occurred in rats injected with PEGylated uricase aggregates. Anti-PEG IgM antibodies, rather than neutralizing antibodies, were found to mediate the ABC. The size of conjugates is important for triggering such phenomena and we speculate that 40-60 nm is the lower size limit that can trigger ABC. Removal of the uricase aggregates and the PEG diol contaminant and modifying with small PEG reagents enabled ABC to be successfully avoided and sufficient reduction in the immunogenicity of 5 kDa mPEG-modified tetrameric canine uricase.

Impact of Large Aggregated Uricases and PEG Diol on Accelerated Blood Clearance of PEGylated Canine Uricase

PubMed Central

Zhang, Chun; Fan, Kai; Ma, Xuefeng; Wei, Dongzhi

2012-01-01

Background Uricase has proven therapeutic value in treating hyperuricemia but sufficient reduction of its immunogenicity may be the largest obstacle to its chronic use. In this study, canine uricase was modified with 5 kDa mPEG-SPA and the impact of large aggregated uricases and cross-linked conjugates induced by difunctional PEG diol on immunogenicity was investigated. Methods and Findings Recombinant canine uricase was first expressed and purified to homogeneity. Source 15Q anion-exchange chromatography was used to separate tetrameric and aggregated uricase prior to pegylation, while DEAE anion-exchange chromatography was used to remove Di-acid PEG (precursor of PEG diol) from unfractionated 5 kDa mPEG-propionic acid. Tetrameric and aggregated uricases were separately modified with the purified mPEG-SPA. In addition, tetrameric uricases was modified with unfractionated mPEG-SPA, resulting in three types of 5 kDa mPEG-SPA modified uricase. The conjugate size was evaluated by dynamic light scattering and transmission electron microscope. The influence of differently PEGylated uricases on pharmacokinetics and immunogenicity were evaluated in vivo. The accelerated blood clearance (ABC) phenomenon previously identified for PEGylated liposomes occurred in rats injected with PEGylated uricase aggregates. Anti-PEG IgM antibodies, rather than neutralizing antibodies, were found to mediate the ABC. Conclusions The size of conjugates is important for triggering such phenomena and we speculate that 40–60 nm is the lower size limit that can trigger ABC. Removal of the uricase aggregates and the PEG diol contaminant and modifying with small PEG reagents enabled ABC to be successfully avoided and sufficient reduction in the immunogenicity of 5 kDa mPEG-modified tetrameric canine uricase. PMID:22745806

Copper Metal from Malachite Circa 4000 B.C.E.

ERIC Educational Resources Information Center

Yee, Gordon T.; Eddleton, Jeannine E.; Johnson, Cris E.

2004-01-01

The feasibility of the laboratory production of copper metal from a readily available, naturally occurring mineral malachite utilizing techniques that are consistent with the time period of around 4000 B.C.E. is presented. The starting materials are inexpensive and convenient and the procedure involves no hazardous reagents and produces no…

29 CFR 4000.24 - What if I mail my submission or issuance using the U.S. Postal Service?

Code of Federal Regulations, 2010 CFR

2010-07-01

.... Postal Service? 4000.24 Section 4000.24 Labor Regulations Relating to Labor (Continued) PENSION BENEFIT... and Issuance Dates § 4000.24 What if I mail my submission or issuance using the U.S. Postal Service... (b) of this section. You deposit your issuance in a mailbox at 4 p.m. on Friday, March 15 and the...

Assessment of PLGA-PEG-PLGA Copolymer Hydrogel for Sustained Drug Delivery in the Ear

PubMed Central

Feng, Liang; Ward, Jonette A.; Li, S. Kevin; Tolia, Gaurav; Hao, Jinsong; Choo, Daniel I.

2014-01-01

Temperature sensitive copolymer systems were previously studied using modified diffusion cells in vitro for intratympanic injection, and the PLGA-PEG-PLGA copolymer systems were found to provide sustained drug delivery for several days. The objectives of the present study were to assess the safety of PLGA-PEG-PLGA copolymers in intratympanic injection in guinea pigs in vivo and to determine the effects of additives glycerol and poloxamer in PLGA-PEG-PLGA upon drug release in the diffusion cells in vitro for sustained inner ear drug delivery. In the experiments, the safety of PLGA-PEG-PLGA copolymers to inner ear was evaluated using auditory brainstem response (ABR). The effects of the additives upon drug release from PLGA-PEG-PLGA hydrogel were investigated in the modified Franz diffusion cells in vitro with cidofovir as the model drug. The phase transition temperatures of the PLGA-PEG-PLGA copolymers in the presence of the additives were also determined. In the ABR safety study, the PLGA-PEG-PLGA copolymer alone did not affect hearing when delivered at 0.05-mL dose but caused hearing loss after 0.1-mL injection. In the drug release study, the incorporation of the bioadhesive additive, poloxamer, in the PLGA-PEG-PLGA formulations was found to decrease the rate of drug release whereas the increase in the concentration of the humectant additive, glycerol, provided the opposite effect. In summary, the PLGA-PEG-PLGA copolymer did not show toxicity to the inner ear at the 0.05-mL dose and could provide sustained release that could be controlled by using the additives for inner ear applications. PMID:24438444

Very rare outburst of the symbiotic variable AG Peg

NASA Astrophysics Data System (ADS)

Waagen, Elizabeth O.

2015-06-01

The symbiotic variable AG Peg is in outburst, the first one observed since its only known outburst, which occurred in 1860-1870. Currently at visual/V magnitude 7.2 (B=7.8), it is an excellent target for visual, PEP, CCD, and DSLR observers and spectroscopists. The current outburst began after 2015 May 27 UT (T. Markham, Leek, Staffordshire, England, from the BAAVSS online database) and was underway by June 13.90 (A. Kosa-Kiss, Salonta, Romania). AG Peg has a very interesting history. Regarding the 1860-1870 outburst, data collected by E. Zinner (Merrill, 1959, S&T, 18, 9, 490) show AG Peg slowly brightening from visual magnitude 9.2 in 1821 to 8.0 in 1855, then at 6.2 in 1860 and brightening to 6.0 in 1870, then in decline at 6.8 by 1903, and continuing to decline slowly ( 6.9 in 1907, 8.0 in 1920, 8.3 in 1940). Observations in the AAVSO International Database since July 1941 show that the decline has continued without interruption from an average magnitude of 7.7 to an average magnitude of 8.8-9.0 by mid-January 2015. The AAVSO data since 1941 also show the periodic 0.4-magnitude variations ( 825 days) that have been present since the 1920s. Thus, after taking about 10 years to brighten from its minimum magnitude of about 9 to its maximum magnitude of 6.0, and then fading gradually over 140-145 years, AG Peg is now in outburst again. There are no observations of the 1860-1870 outburst that show the outburst's beginning. This time, however, in 2015, the opportunity is here to follow the outburst itself closely and learn just what this system does during outburst. Observations in all bands and visual observations are strongly encouraged. AG Peg is bright enough to be a very good PEP target. For spectroscopists, AG Peg has an extremely complex spectrum that undergoes substantial changes and would make a very interesting target. Finder charts with sequence may be created using the AAVSO Variable Star Plotter (https://www.aavso.org/vsp). Observations should be

Endostar-loaded PEG-PLGA nanoparticles: in vitro and in vivo evaluation.

PubMed

Hu, Sanyuan; Zhang, Yangde

2010-11-24

Endostar, a novel recombinant human endostatin, which was approved by the Chinese State Food and Drug Administration in 2005, has a broad spectrum of activity against solid tumors. In this study, we aimed to determine whether the anticancer effect of Endostar is increased by using a nanocarrier system. It is expected that the prolonged circulation of endostar will improve its anticancer activity. Endostar-loaded nanoparticles were prepared to improve controlled release of the drug in mice and rabbits, as well as its anticancer effects in mice with colon cancer. A protein release system could be exploited to act as a drug carrier. Nanoparticles were formulated from poly (ethylene glycol) modified poly (DL-lactide-co-glycolide) (PEG-PLGA) by a double emulsion technique. Physical and release characteristics of endostar-loaded nanoparticles in vitro were evaluated by transmission electron microscopy (TEM), photon correlation spectroscopy (PCS), and micro bicinchoninic acid protein assay. The pharmacokinetic parameters of endostar nanoparticles in rabbit and mice plasma were measured by enzyme-linked immunosorbent assay. Western blot was used to detect endostatin in different tissues. To study the effects of endostar-loaded nanoparticles in vivo, nude mice in which tumor cells HT-29 were implanted, were subsequently treated with endostar or endostar-loaded PEG-PLGA nanoparticles. Using TEM and PCS, endostar-loaded PEG-PLGA nanoparticles were found to have a spherical core-shell structure with a diameter of 169.56 ± 35.03 nm. Drug-loading capacity was 8.22% ± 2.35% and drug encapsulation was 80.17% ± 7.83%. Compared with endostar, endostar-loaded PEG-PLGA nanoparticles had a longer elimination half-life and lower peak concentration, caused slower growth of tumor cell xenografts, and prolonged tumor doubling times. The nanoparticles changed the pharmacokinetic characteristics of endostar in mice and rabbits, thereby reinforcing anticancer activity. In conclusion, PEG

Current status of percutaneous endoscopic gastrostomy (PEG) in a general hospital in Japan: a cross-sectional study

PubMed Central

Kusano, Chika; Yamada, Nobuo; Kikuchi, Kenji; Hashimoto, Masaji; Gotoda, Takuji

2016-01-01

Background: There has been debate over the indications for percutaneous endoscopic gastrostomy (PEG) in recent years in Japan. In addition, the level of satisfaction of patients and patient’s family after PEG remains unclear. The aim of this study was to investigate the current status of PEG and the level of satisfaction of patients and patients’ families after PEG in Japan. Methods: We reviewed the existing data of all patients who underwent PEG tube insertion at Yuri Kumiai General Hospital (Akita, Japan) between February 2000 and December 2010. We examined the following points: underlying diseases requiring PEG, levels of consciousness, and performance status. We also sent a questionnaire to the patients and patient’s families to ask about their satisfaction with and thoughts about PEG. Results: The data of 545 patients who underwent PEG were reviewed. There were 295 men and 250 women, with a mean age of 77.2 ± 11.4 years. PEG was indicated most frequently for cerebrovascular disorders (48.2%, 239/545). There were 515 (94.4%, 515/545) patients showing consciousness disturbance and 444 (81.5%, 444/545) bedridden patients. The questionnaire was answered by one patient himself and 316 patients’ families. When asked, “Was performing PEG a good decision?”, 57.5% (182/316) of the patients’ families answered yes. Meanwhile, when patients’ family members were asked if they would wish to undergo PEG if they were in the same condition as the patient, 28.4% (90/316) answered yes, whereas 55.3% (175/316) answered no. Conclusions: Few patients were able to make their own decision about PEG tube placement because of consciousness disturbance. As a result, many family members of the patients did not want to experience PEG for themselves. Future studies should be performed to clarify the quality of life and ethical aspects associated with PEG. PMID:27313796

Drug release patterns and cytotoxicity of PEG-poly(aspartate) block copolymer micelles in cancer cells.

PubMed

Eckman, Allison M; Tsakalozou, Eleftheria; Kang, Nayon Y; Ponta, Andrei; Bae, Younsoo

2012-07-01

To test physicochemical and biological properties of PEG-poly(aspartate) [PEG-p(Asp)] block copolymer micelles entrapping doxorubicin hydrochloride (DOX) through ionic interaction. PEG-p(Asp) was synthesized from 5 kDa PEG and 20 Asp units. Carboxyl groups of p(Asp) were present as benzyl ester [PEG-p(Asp/Bz)], sodium salt [PEG-p(Asp/Na)] or free acid [PEG-p(Asp/H)]. Block copolymers and DOX were mixed at various ratios to prepare polymer micelles, which were subsequently characterized to determine particle size, drug loading and release patterns, and cytotoxicity against prostate (PC3 and DU145) and lung (A549) cancer cell lines. PEG-p(Asp/Bz), Na- and H-micelles entrapped 1.1, 56.8 and 40.6 wt.% of DOX, respectively. Na- and H-micelles (<100 nm) showed time-dependent DOX release at pH 7.4, which was accelerated at pH 5.0. Na-micelles were most stable at pH 7.4, retaining 31.8% of initial DOX for 48 h. Cytotoxicity of Na-micelles was 23.2% (A549), 28.5% (PC3) and 45.9% (DU145) more effective than free DOX. Ionic interaction appeared to entrap DOX efficiently in polymer micelles from PEG-p(Asp) block copolymers. Polymer micelles possessing counter ions (Na) of DOX in the core were the most stable, releasing drugs for prolonged time in a pH-dependent manner, and suppressing cancer cells effectively.

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

PubMed

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

2014-11-28

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

Stabilization of Resveratrol in Blood Circulation by Conjugation to mPEG and mPEG-PLA Polymers: Investigation of Conjugate Linker and Polymer Composition on Stability, Metabolism, Antioxidant Activity and Pharmacokinetic Profile

PubMed Central

Siddalingappa, Basavaraj; Benson, Heather A. E.; Brown, David H.; Batty, Kevin T.; Chen, Yan

2015-01-01

Resveratrol is naturally occurring phytochemical with diverse biological activities such as chemoprevention, anti-inflammatory, anti-cancer, anti-oxidant. But undergoes rapid metabolism in the body (half life 0.13h). Hence Polymer conjugation utilizing different chemical linkers and polymer compositions was investigated for enhanced pharmacokinetic profile of resveratrol. Ester conjugates such as α-methoxy-ω-carboxylic acid poly(ethylene glycol) succinylamide resveratrol (MeO-PEGN-Succ-RSV) (2 and 20 kDa); MeO-PEG succinyl ester resveratrol (MeO-PEGO-Succ-RSV) (2 kDa); α-methoxy poly(ethylene glycol)-co-polylactide succinyl ester resveratrol (MeO-PEG-PLAO-Succ-RSV) (2 and 6.6kDa) were prepared by carbodiimide coupling reactions. Resveratrol-PEG ethers (2 and 5 kDa) were synthesized by alkali-mediated etherification. All polymer conjugates were fully characterized in vitro and the pharmacokinetic profile of selected conjugates was characterized in rats. Buffer and plasma stability of conjugates was dependent on polymer hydrophobicity, aggregation behavior and PEG corona, with MeO-PEG-PLAO-Succ-RSV (2 kDa) showing a 3h half-life in rat plasma in vitro. Polymer conjugates irrespective of linker chemistry protected resveratrol against metabolism in vitro. MeO-PEG-PLAO-Succ-RSV (2 kDa), Resveratrol-PEG ether (2 and 5 kDa) displayed improved pharmacokinetic profiles with significantly higher plasma area under curve (AUC), slower clearance and smaller volume of distribution, compared to resveratrol. PMID:25799413

Enzyme-Regulated Fast Self-Healing of a Pillararene-Based Hydrogel.

PubMed

Zhang, Xin; Xu, Jiayun; Lang, Chao; Qiao, Shanpeng; An, Guo; Fan, Xiaotong; Zhao, Linlu; Hou, Chunxi; Liu, Junqiu

2017-06-12

Self-healing, one of the exciting properties of materials, is frequently used to repair the damage of biological and artificial systems. Here we have used enzymatic catalysis approaches to develop a fast self-healing hydrogel, which has been constructed by dynamic aldimine cross-linking of pillar[5]arene-derivant and dialdehyde-functionalized PEG followed by encapsulation of glucose oxidase (GOx) and catalase (CAT). In specific, the two hydroxyl groups at terminal of PEG 4000 are functionalized with benzaldehydes that can interact with amino-containing pillar[5]arene-derivant through dynamic aldimine cross-links, resulting in reversible dynamic hydrogels. Modulus analysis indicated that storage modulus (G') and loss modulus (G″) of the hydrogel increased obviously as the concentration of dialdehyde-functionalized PEG 4000 (DF-PEG 4000 ) increased or the pH values decreased. Once glucose oxidase (GOx) and catalase (CAT) are located, the hydrogel could be fast repaired, with self-healing efficiency up to 100%. Notably tensile test showed that the repair process of pillararene-based hydrogel can finish in several minutes upon enzyme catalysis, while it needed more than 24 h to achieve this recovery without enzymes. This enzyme-regulated self-healing hydrogel would hold promise for delivering drugs and for soft tissue regeneration in the future.

The efficacy of nimodipine drug delivery using mPEG-PLA micelles and mPEG-PLA/TPGS mixed micelles.

PubMed

Huang, Shuling; Yu, Xiaohong; Yang, Linlin; Song, Fenglan; Chen, Gang; Lv, Zhufen; Li, Tiao; Chen, De; Zhu, Wanhua; Yu, Anan; Zhang, Yongming; Yang, Fan

2014-10-15

In order to develop and compare mPEG-PLA micelles and mPEG-PLA/TPGS mixed micelles, with the intention to develop a highly efficient formulation for nimodipine (NIM), NIM-loaded micelles and mixed micelles were made and their pharmacokinetics were studied. Single factor experiments and orthogonal experiments were designed to optimize the final preparation process, characterizations and drug release behaviors were studied. Pharmacokinetics of NIM micelles, NIM mixed micelles were researched and were compared to NIM solution. Micelles and mixed micelles were prepared by solvent evaporation method, with relatively high drug loading efficiency and within nano-particle size range. The CMC value of mPEG-PLA was lower than that of mPEG-PLA/TPGS. The results of FTIR and TEM confirmed the spherical core-shell structure of micelles as well as mixed micelles, and the encapsulation of NIM inside the cores. In vitro release showed that micelles and mixed micelles had sustained release effect in the forms of passive diffusion and dissolution process, respectively. Following intraperitoneal administration (5mg/kg), micelles and mixed micelles were absorbed faster than solution, and with larger MRT(0-t), smaller CLz and larger AUC(0-t) as compared to that of solution, which showed micelles and mixed micelles had higher retention, slower elimination and higher bioavailability. This experiment also showed that mixed micelles released NIM more stably than micelles. By evaluate the bioequivalence, NIM micelles and NIM mixed micelles were testified non-bioequivalent to NIM solution. Micelles and mixed micelles could sustain the NIM concentrations more efficiently in plasma as compared to solution. Mixed micelles were the best ones since they had high loading content and released more stably. Thus, apprehending micelles and mixed micelles were suited as poor aqueous solubility drug carriers, and mixed micelles were better due to their high loading content and more stable release

PEG and Thickeners: A Critical Interaction Between Polyethylene Glycol Laxative and Starch-Based Thickeners.

PubMed

Carlisle, Brian J; Craft, Garrett; Harmon, Julie P; Ilkevitch, Alina; Nicoghosian, Jenik; Sheyner, Inna; Stewart, Jonathan T

2016-09-01

Clinicians commonly encounter dysphagia and constipation in a skilled nursing population. Increasing the viscosity of liquids, usually with a starch- or xanthan gum-based thickener, serves as a key intervention for patients with dysphagia. We report a newly identified and potentially dangerous interaction between polyethylene glycol 3350 laxative (PEG) and starch-thickened liquids. A patient requiring nectar-thickened liquids became constipated, and medical staff prescribed PEG for constipation. His nurse observed that the thickened apple juice immediately thinned to near-water consistency when PEG was added. She obtained the same results with thickened water and coffee. We quantified this phenomenon by isothermal rotational rheology. Results confirmed a precipitous loss of thickening when PEG was added to starch-based thickeners but not with xanthan gum-based thickeners. Clinicians and front-line staff should be aware of this potentially critical interaction between PEG- and starch-based thickeners. Although confirmatory studies are needed, our preliminary data suggest that PEG may be compatible with xanthan gum-- based thickeners. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. All rights reserved.

mPEG-PLA Micelle for Delivery of Effective Parts of Andrographis Paniculata.

PubMed

Yao, Hailu; Song, Shiyong; Miao, Xiaolu; Liu, Xiao; Zhao, Junli; Wang, Zhen; Shao, Xiaoting; Zhang, Yu; Han, Guang

2018-01-01

Many studies have shown that Andrographis paniculata (Burm. f.) Nees has a good anti-tumor effect, but poor solubility in water and poor bioavailability hinder the modernization of it. To formulate the effective parts (mainly diterpene lactones) of Andrographis paniculata (AEP) into targeting drug delivery system, a series of poly(ethylene glycol)-poly(D.L-lactic acid)(mPEG-PLA) with different ratio of hydrophilic and hydrophobic segment was synthetized to encapsulate AEP. AEP micelles were prepared by a simple solvent-evaporation method. According to the loading capacity, the best polymer was chosen. mPEG-PLA micelles were characterized in terms of drug entrapping efficiency, loading capacity, size, the crystalline state of AEP, stability and release profile. Meanwhile, the cytotoxicity of micelles on mouse breast cancer 4T-1 was investigated. These micelle (mPEG-PLA-AEP) particles had a size of (92.84±5.63) nm and a high entrapping efficiency and loading capacity of (91.00±11.53)% and (32.14±3.02)%(w/w), respectively. The powder DSC showed that drugs were well encapsulated in the core of micelles. mPEG-PLA-AEP had a good stability against salt dissociation, protein adsorption and anion substitution and the solubility of andrographolide (AG) and 14-deoxy-11,12-didehydroandrographolide(DDAG) in AEP increased 4.51 times and 2.12 times in water, and the solubility of DAG showed no difference. mPEG-PLA-AEP had the same release profile in different dissolution medium. Cytotoxicity testing in vitro demonstrated that mPEG-PLA-AEP exhibited higher cell viability inhibition in mouse breast cancer 4T-1 than free AEP. mPEG-PLA micelles offer a promising alternative for TCM therapy with higher solubility and improved antitumor effect. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Gadolinium-conjugated PLA-PEG nanoparticles as liver targeted molecular MRI contrast agent.

PubMed

Chen, Zhijin; Yu, Dexin; Liu, Chunxi; Yang, Xiaoyan; Zhang, Na; Ma, Chunhong; Song, Jibin; Lu, Zaijun

2011-09-01

A nanoparticle magnetic resonance imaging (MRI) contrast agent targeted to liver was developed by conjugation of gadolinium (Gd) chelate groups onto the biocompatible poly(l-lactide)-block-poly (ethylene glycol) (PLA-PEG) nanoparticles. PLA-PEG conjugated with diethylenetriaminopentaacetic acid (DTPA) was used to formulate PLA-PEG-DTPA nanoparticles by solvent diffusion method, and then Gd was loaded onto the nanoparticles by chelated with the unfolding DTPA on the surface of the PLA-PEG-DTPA nanoparticles. The mean size of the nanoparticles was 265.9 ± 6.7 nm. The relaxivity of the Gd-labeled nanoparticles was measured, and the distribution in vivo was evaluated in rats. Compared with conventional contrast agent (Magnevist), the Gd-labeled PLA-PEG nanoparticles showed significant enhancement both on liver targeting ability and imaging signal intensity. The T(1) and T(2) relaxivities per [Gd] of the Gd-labeled nanoparticles was 18.865 mM(-1) s(-1) and 24.863 mM(-1) s(-1) at 3 T, respectively. In addition, the signal intensity in vivo was stronger comparing with the Gd-DTPA and the T(1) weight time was lasting for 4.5 h. The liver targeting efficiency of the Gd-labeled PLA-PEG nanoparticles in rats was 14.57 comparing with Magnevist injection. Therefore, the Gd-labeled nanoparticles showed the potential as targeting molecular MRI contrast agent for further clinical utilization.

Electrothermal Microactuators With Peg Drive Improve Performance for Brain Implant Applications

PubMed Central

Anand, Sindhu; Sutanto, Jemmy; Baker, Michael S.; Okandan, Murat; Muthuswamy, Jit

2013-01-01

This paper presents a new actuation scheme for in-plane bidirectional translation of polysilicon microelectrodes. The new Chevron-peg actuation scheme uses microelectromechanical systems (MEMS) based electrothermal microactuators to move microelectrodes for brain implant applications. The design changes were motivated by specific needs identified by the in vivo testing of an earlier generation of MEMS microelectrodes that were actuated by the Chevron-latch type of mechanism. The microelectrodes actuated by the Chevron-peg mechanism discussed here show improved performance in the following key areas: higher force generation capability (111 μN per heat strip compared to 50 μN), reduced power consumption (91 mW compared to 360 mW), and reliable performance with consistent forward and backward movements of microelectrodes. Failure analysis of the Chevron-latch and the Chevron-peg type of actuation schemes showed that the latter is more robust to wear over four million cycles of operation. The parameters for the activation waveforms for Chevron-peg actuators were optimized using statistical analysis. Waveforms with a 1-ms time period and a 1-Hz frequency of operation showed minimal error between the expected and the actual movement of the microelectrodes. The new generation of Chevron-peg actuators and microelectrodes are therefore expected to enhance the longevity and performance of implanted microelectrodes in the brain.  [2011-0341] PMID:24431926

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

PubMed

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

2013-05-01

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

[Study on the stability of chicken egg yolk immunoglobulin (IgY) modified with mPEG].

PubMed

Wang, Li-Ying; Ma, Mei-Hu; Huang, Qun; Shi, Xiao-Xia

2012-09-01

The objective of the present paper was to study the effect of monomethoxypolyethlene glycol (mPEG) modification on the stability of chicken IgY and compare the stability of the modification products by Fourier transform infrared spectroscopy (FTIR), CD spectrooscopy and fluorescence spectroscopy. NHS-mPEG was used to modify IgY after mPEG was activated with N-hydroxysuccinimide (NHS). The optimal reaction condition for modification was 1:10 molar rate of IgY to mPEG at pH 7, reaction for 1 h, and the product was obtained with modification rate of 20.56% and activity reservation of 87. 62%. In addition, the thermal and pH stability of IgY and mPEG-IgY was compared by spectroscopic methods. The results showed that the alpha-helix, beta-sheet, beta-turn, and random content of IgY changed from 14.5%, 42.1%, 6.2% and 37.2% to 1.6%, 55.25%, 5.8% and 37.5%, while mPEG changed from 12.9%, 42.7%, 6.3% and 38. 1% to 3.1%, 50.5%, 7.2% and 39.2%, respectively, after incubating for 120 min at 70 degrees C. For the treatment with acid-base, similarly, the structure changes of mPEG-IgY were smaller than IgY. Thus, it is indicated that IgY modified by mPEG had greater stable properties.

A Retrospective Study of Association between Peg-shaped Maxillary Lateral Incisors and Dental Anomalies.

PubMed

Kim, Jae-Hwan; Choi, Nam-Ki; Kim, Seon-Mi

The purpose of this study was to investigate the prevalence of peg-shaped maxillary lateral incisors and the incidence of associated dental anomalies in children. We investigated the prevalence of peg-laterals and incidence of associated dental anomalies in 3,834 children aged 7-15 who visited the Department of Pediatric Dentistry from January 2010 to December 2015 and underwent panoramic radiographs. The prevalence of peg-laterals was 1.69% in boys, 1.75% in girls, and 1.72% overall. Among children with peg-laterals, the frequencies of associated dental anomalies were as follows: congenitally missing teeth, 31.8%; dens invaginatus, 19.7%; palatally displaced canines, 12.1%; supernumerary teeth, 7.6%; and transposition, 7.6%. As children with peg-laterals have a higher incidence of other dental anomalies, careful consideration is needed when planning diagnosis and treatment.

Bowel preparations for colonoscopy: an RCT.

PubMed

Di Nardo, Giovanni; Aloi, Marina; Cucchiara, Salvatore; Spada, Cristiano; Hassan, Cesare; Civitelli, Fortunata; Nuti, Federica; Ziparo, Chiara; Pession, Andrea; Lima, Mario; La Torre, Giuseppe; Oliva, Salvatore

2014-08-01

The ideal preparation regimen for pediatric colonoscopy remains elusive, and available preparations continue to represent a challenge for children. The aim of this study was to compare the efficacy, safety, tolerability, and acceptance of 4 methods of bowel cleansing before colonoscopy in children. This randomized, investigator-blinded, noninferiority trial enrolled all children aged 2 to 18 years undergoing elective colonoscopy in a referral center for pediatric gastroenterology. Patients were randomly assigned to receive polyethylene glycol (PEG) 4000 with simethicon (PEG-ELS group) or PEG-4000 with citrates and simethicone plus bisacodyl (PEG-CS+Bisacodyl group), or PEG 3350 with ascorbic acid (PEG-Asc group), or sodium picosulfate plus magnesium oxide and citric acid (NaPico+MgCit group). Bowel cleansing was evaluated according to the Boston Bowel Preparation Scale. The primary end point was overall colon cleansing. Tolerability, acceptability, and compliance were also evaluated. Two hundred ninety-nine patients were randomly allocated to the 4 groups. In the per-protocol analysis, PEG-CS+Bisacodyl, PEG-Asc, and NaPico+MgCit were noninferior to PEG-ELS in bowel-cleansing efficacy of both the whole colon (P = .910) and colonic segments. No serious adverse events occurred in any group. Rates of tolerability, acceptability, and compliance were significantly higher in the NaPico+MgCit group. Low-volume PEG preparations (PEG-CS+Bisacodyl, PEG-Asc) and NaPico+MgCit are noninferior to PEG-ELS in children, representing an attractive alternative to high-volume regimens in clinical practice. Because of the higher tolerability and acceptability profile, NaPico+MgCit would appear as the most suitable regimen for bowel preparation in children. Copyright © 2014 by the American Academy of Pediatrics.

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

PubMed

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

2012-07-01

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

Pharmacometrics and delivery of novel nanoformulated PEG-b-poly(ε-caprolactone) micelles of rapamycin

PubMed Central

Yáñez, Jaime A.; Forrest, M. Laird; Ohgami, Yusuke

2008-01-01

Purpose To determine the pharmacokinetics, tissue, and blood distribution of rapamycin PEG-block-poly(ε-caprolactone) (PEG-b-PCL) micelle formulations with and without the addition of α-tocopherol compared to control rapamycin in Tween 80/PEG 400/N,N-dimethylacetamide (DMA) (7:64:29). Methods Rapamycin was incorporated at 10% w/w into PEG-b-PCL micelles (5:10 kDa) using a solvent extraction technique. The co-incorporation of 2:1 α-tocopherol:PEG-b-PCL was also studied. Rapamycin was quantified utilizing LC/MS in a Waters XTerra MS C18 column with 32-desmethoxyrapamycin as the internal standard. Male Sprague Dawley rats (N = 4 per group; ~200 g) were cannulated via the left jugular and dosed intravenously (IV) with the rapamycin control and micelle formulations (10 mg/kg, 1:9 ratio for rapamycin to PEG-b-PCL). For tissue distribution 24 h after IV dosing, whole blood, plasma, red blood cells, and all the representative tissues were collected. The tissues were rapidly frozen under liquid nitrogen and ground to a fine powder. The rapamycin concentrations in plasma and red blood cells were utilized to determine the blood distribution (partition coefficient between plasma and red blood cells). For the determination of the pharmacokinetic parameters, blood, plasma, and urine samples were collected over 48 h. The pharmacokinetic parameters were calculated using WinNonlin® (Version 5.1) software. Results Rapamycin concentrations were considerably less in brain after administration of both micelle formulations compared to a rapamycin in the Tween 80/PEG 400/DMA control group. There was a 2-fold and 1.6-fold increase in the plasma fraction for rapamycin micelles with and without α-tocopherol. There was a decrease in volume of distribution for both formulations, an increase in AUC, a decrease in clearance, and increase in half life respectively for rapamycin in PEG-b-PCL + α-tocopherol micelles and in PEG-b-PCL micelles. There was no mortality with the micelle

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

PubMed

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

2009-03-09

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

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

PubMed

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

2017-09-01

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

PLGA-PEG-PLGA hydrogel for ocular drug delivery of dexamethasone acetate.

PubMed

Gao, Yuan; Sun, Yan; Ren, Fuzheng; Gao, Shen

2010-10-01

This study aims to investigate the suitability of thermosensitive triblock polymer poly-(DL-lactic acid-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA as a matrix material for ocular delivery of dexamethasone acetate (DXA). The copolymer was synthesized and evaluated for its thermosensitive and gelation properties. DXA in situ gel-forming solution based on PLGA-PEG-PLGA copolymer of 20% (w/w) was prepared and evaluated for ocular pharmacokinetics in rabbit according to the microdialysis method, which was compared to the normal eye drop. The copolymer with 20% (w/w) had a low critical solution temperature of 32 degrees C, which is close to the surface temperature of the eye. The C(max) of DXA in the anterior chamber for the PLGA-PEG-PLGA solution was 125.2 microg/mL, which is sevenfold higher than that of the eye drop, along with greater area under the concentration-time curves (AUC). These results suggest that the PLGA-PEG-PLGA copolymer is potential thermosensitive in situ gel-forming material for ocular drug delivery, and it may improve the bioavailability, efficacy of some eye drugs.

Synthesis and in vitro cytotoxicity of mPEG-SH modified gold nanorods

NASA Astrophysics Data System (ADS)

Didychuk, Candice L.; Ephrat, Pinhas; Belton, Michelle; Carson, Jeffrey J. L.

2008-02-01

Plasmon-resonant gold nanorods show great potential as an agent for contrast-enhanced biomedical imaging or for phototherapeutics. This is primarily due to the high molar extinction coefficient at the absorption maximum and the dependence of the wavelength of the absorption maximum on the aspect ratio, which is tunable in the near-infrared (NIR) during synthesis. Although gold nanorods can be produced in high-yield through the seed-mediated growth technique, the presence of residual cetyltrimethylammonium bromide (CTAB), a stabilizing surfactant required for nanorod growth, interferes with cell function and causes cytotoxicity. To overcome this potential obstacle to in vivo use, we synthesized gold nanorods and conjugated them to a methoxy (polyethylene glycol)-thiol (mPEG (5000)-SH). This approach yielded mPEG-SH modified gold nanorods with optical and morphometric properties that were similar to raw (CTAB) nanorods. Both the CTAB and mPEG-SH nanorods were tested for cytotoxicity against the HL-60 human leukemia cell line by trypan blue exclusion, and the mPEG-SH modified gold nanorods were also tested against a rat insulinoma (RIN-38) and squamous cell carcinoma (SCCVII) cell line. Cells incubated for 24 h with the mPEG-SH modified nanorods had little change in cell viability compared to cells incubated with vehicle alone. This was in contrast to cytotoxicity of CTAB nanorods on HL-60 cells. These results suggest that mPEG-SH modified gold nanorods are better suited for cell loading protocols and injection into animals and facilitate their use for imaging and phototherapeutic purposes.

Alternating block polyurethanes based on PCL and PEG as potential nerve regeneration materials.

PubMed

Li, Guangyao; Li, Dandan; Niu, Yuqing; He, Tao; Chen, Kevin C; Xu, Kaitian

2014-03-01

Polyurethanes with regular and controlled block arrangement, i.e., alternating block polyurethanes (abbreviated as PUCL-alt-PEG) based on poly(ε-caprolactone) (PCL-diol) and poly(ethylene glycol) (PEG) was prepared via selectively coupling reaction between PCL-diol and diisocyanate end-capped PEG. Chemical structure, molecular weight, distribution, and thermal properties were systematically characterized by FTIR, (1)H NMR, GPC, DSC, and TGA. Hydrophilicity was studied by static contact angle of H2O and CH2I2. Film surface was observed by scanning electron microscope (SEM) and atomic force microscopy, and mechanical properties were assessed by universal test machine. Results show that alternating block polyurethanes give higher crystal degree, higher mechanical properties, and more hydrophilic and rougher (deep ravine) surface than their random counterpart, due to regular and controlled structure. Platelet adhesion illustrated that PUCL-alt-PEG has better hemocompatibility and the hemacompatibility was affected significantly by PEG content. Excellent hemocompatibility was obtained with high PEG content. CCK-8 assay and SEM observation revealed much better cell compatibility of fibroblast L929 and rat glial cells on the alternating block polyurethanes than that on random counterpart. Alternating block polyurethane PUC20-a-E4 with optimized composition, mechanical, surface properties, hemacompatibility, and highest cell growth and proliferation was achieved for potential use in nerve regeneration. Copyright © 2013 Wiley Periodicals, Inc.

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

NASA Astrophysics Data System (ADS)

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

2016-05-01

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

Degradation prediction model and stem cell growth of gelatin-PEG composite hydrogel.

PubMed

Zhou, Nan; Liu, Chang; Lv, Shijie; Sun, Dongsheng; Qiao, Qinglong; Zhang, Rui; Liu, Yang; Xiao, Jing; Sun, Guangwei

2016-12-01

Gelatin hydrogel has great potential in regenerative medicine. The degradation of gelatin hydrogel is important to control the release profile of encapsulated biomolecules and regulate in vivo tissue repair process. As a plasticizer, PEG can significantly improve the mechanical property of gelatin hydrogel. However, how preparation parameters affect the degradation rate of gelatin-PEG composite hydrogel is still not clear. In this study, the significant effect factor, glutaraldehyde (GA) concentration, was confirmed by means of Plackett-Burman method. Then a mathematical model was built to predict the degradation rate of composite hydrogels under different preparation conditions using the response surface method (RSM), which was helpful to prepare the certain composite hydrogel with desired degradation rate. In addition, it was found that gelatin-PEG composite hydrogel surface well supported the adhesion and growth of human mesenchymal stem cells (MSCs). Moreover, PEG concentration not only could adjust hydrogel degradation more subtly, but also might increase the cross-linking degree and affect the cell migration. Therefore, these results would be useful to optimize the preparation of gelatin-PEG composite hydrogel for drug delivery or tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 3149-3156, 2016. © 2016 Wiley Periodicals, Inc.

The exploration of endocytic mechanisms of PLA-PEG nanoparticles prepared by coaxialtri-capillary electrospray-template removal method.

PubMed

Chen, Jiaming; Cao, Lihua; Cui, Yuecheng; Tu, Kehua; Wang, Hongjun; Wang, Li-Qun

2018-01-01

The nano-sized poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) particles with core-shell structure were efficiently prepared by using coaxial tri-capillary electrospray-template removal method. The cellular uptake mechanism, intracellular distribution and exocytosis in A549 cell model of electrosprayed PLA-PEG nanoparticles were systemically studied. The drug release behavior of electrosprayed PLA-PEG nanoparticles were also investigated. Our results showed that PLA-PEG nanoparticles can be endocytosed quickly by A549 cells. The cellular uptake of PLA-PEG nanoparticles was an energy dependent endocytosis process. Caveolae-mediated endocytosis was only one of endocytosis pathways in A549 cells for PLA-PEG nanoparticles, while clathrin mediated endocytosis was not involved in the endocytosis process. The endocytosed PLA-PEG nanoparticles enriched in the head of A549 cells and only a small amount of them was transported into lysosome after 24h incubation. These findings provided insights into the application of electrosprayed PLA-PEG nanoparticles in nano drug delivery field. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2016-10-01

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

X-ray studies of recombinant anti-testosterone Fab fragments: the use of PEG 3350 in crystallization.

PubMed

Valjakka, J; Hemminki, A; Teerinen, T; Takkinen, K; Rouvinen, J

2000-02-01

Recombinant anti-testosterone wild-type Fab fragment and mutant Fab fragments with high binding selectivity developed by protein engineering have been crystallized with and without ligands. Crystals of these Fab fragments were obtained by the vapour-diffusion technique at room temperature using solutions of PEG 3350 with various biological buffers and with a wide pH range. So far, five data sets have been collected from crystals of three Fab-antigen complexes and from two uncomplexed Fab fragments, with resolutions ranging from 2.10 to 3.1 A. Crystallization conditions for Fab fragments were found by using modifications of the low ionic strength PEG 3350 series. Suitable concentrations of PEG 400, MPD and glycerol solutions for use as cryoprotectants in PEG 3350 solutions have been determined. One useful observation was that PEG 3350 is able to work alone as a cryoprotectant. The screening protocol used requires a smaller amount of protein material to achieve auspicious pre-crystals than previously. Results support the claim that PEG 3350 is more suitable for the crystallization of Fab fragments than higher molecular weight PEGs.

Effect of DSPE-PEG on compound action potential, injury potential and ion concentration following compression in ex vivo spinal cord.

PubMed

Wang, Aihua; Huo, Xiaolin; Zhang, Guanghao; Wang, Xiaochen; Zhang, Cheng; Wu, Changzhe; Rong, Wei; Xu, Jing; Song, Tao

2016-05-04

It has been shown that polyethylene glycol (PEG) can reseal membrane disruption on the spinal cord, but only high concentrations of PEG have been shown to have this effect. Therefore, the effect of PEG is somewhat limited, and it is necessary to investigate a new approach to repair spinal cord injury. This study assesses the ability of 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly (ethylene glycol)) 2000] (DSPE-PEG) to recover physiological function and attenuate the injury-induced influx of extracellular ions in ex vivo spinal cord injury. Isolated spinal cords were subjected to compression injury and treated with PEG or DSPE-PEG immediately after injury. The compound action potential (CAP) was recorded before and after injury to assess the functional recovery. Furthermore, injury potential, the difference in gap potentials before and after compression, and the concentration of intracellular ions were used to evaluate the effect of DSPE-PEG on reducing ion influx. Data showed that the injury potential and ion concentration of the untreated, PEG and DSPE-PEG group, without significant difference among them, are remarkably higher than those of the intact group. Moreover, the CAP recovery of the DSPE-PEG and PEG treated spinal cords was significantly greater than that of the untreated spinal cords. The level of CAP recovery in the DSPE-PEG and PEG treated groups was the same, but the concentration of DSPE-PEG used was much lower than the concentration of PEG. These results suggest that instant application of DSPE-PEG could effectively repair functional disturbance in SCI at a much lower concentration than PEG. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effect of PEG-PDLLA polymeric nanovesicles loaded with doxorubicin and hematoporphyrin monomethyl ether on human hepatocellular carcinoma HepG2 cells in vitro.

PubMed

Xiang, Guang-Hua; Hong, Guo-Bin; Wang, Yong; Cheng, Du; Zhou, Jing-Xing; Shuai, Xin-Tao

2013-01-01

To evaluate the cytotoxicity of poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-PDLLA) nanovesicles loaded with doxorubicin (DOX) and the photosensitizer hematoporphyrin monomethyl ether (HMME) on human hepatocellular carcinoma HepG2 cells and to investigate potential apoptotic mechanisms. PEG-PDLLA nanovesicles were simultaneously loaded with DOX and HMME (PEG-PDLLA-DOX-HMME), and PEG-PDLLA nanovesicles were loaded with DOX (PEG-PDLLA-DOX), HMME (PEG-PDLLA-HMME), or the PEG-PDLLA nanovesicle alone as controls. The cytotoxicity of PEG-PDLLA-DOX-HMME, PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA against HepG2 cells was measured, and the cellular reactive oxygen species, percentage of cells with mitochondrial membrane potential depolarization, and apoptotic rate following treatment were determined. Four nanovesicles (PEG-PDLLA-DOX-HMME, PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA) were synthesized, and mean particle sizes were 175±18 nm, 154±3 nm, 196±2 nm, and 147±15 nm, respectively. PEG-PDLLA-DOX-HMME was more cytotoxic than PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA. PEG-PDLLA-HMME-treated cells had the highest mean fluorescence intensity, followed by PEG-PDLLA-DOX-HMME-treated cells, whereas PEG-PDLLA-DOX- and PEG-PDLLA-treated cells had a similar fluorescence intensity. Mitochondrial membrane potential depolarization was observed in 54.2%, 59.4%, 13.8%, and 14.8% of the cells treated with PEG-PDLLA-DOX-HMME, PEG-PDLLA-HMME, PEG-PDLLA-DOX, and PEG-PDLLA, respectively. The apoptotic rate was significantly higher in PEG-PDLLA-DOX-HMME-treated cells compared with PEG-PDLLA-DOX- and PEG-PDLLA-HMME-treated cells. The PEG-PDLLA nanovesicle, a drug delivery carrier, can be simultaneously loaded with two anticancer drugs (hydrophilic DOX and hydrophobic HMME). PEG-PDLLA-DOX-HMME cytotoxicity to HepG2 cells is significantly higher than the PEG-PDLLA nanovesicle loaded with DOX or HMME alone, and DOX and HMME have a synergistic effect against human

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

PubMed Central

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

2014-01-01

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

Towards Virtual FLS: Development of a Peg Transfer Simulator

PubMed Central

Arikatla, Venkata S; Ahn, Woojin; Sankaranarayanan, Ganesh; De, Suvranu

2014-01-01

Background Peg transfer is one of five tasks in the Fundamentals of Laparoscopic Surgery (FLS), program. We report the development and validation of a Virtual Basic Laparoscopic Skill Trainer-Peg Transfer (VBLaST-PT©) simulator for automatic real-time scoring and objective quantification of performance. Methods We have introduced new techniques in order to allow bi-manual manipulation of pegs and automatic scoring/evaluation while maintaining high quality of simulation. We performed a preliminary face and construct validation study with 22 subjects divided into two groups: experts (PGY 4–5, fellow and practicing surgeons) and novice (PGY 1–3). Results Face validation shows high scores for all the aspects of the simulation. A two-tailed Mann-Whitney U-test scores showed significant difference between the two groups on completion time (p=0.003), FLS score (p=0.002) and the VBLaST-PT© score (p=0.006). Conclusions VBLaST-PT© is a high quality virtual simulator that showed both face and construct validity. PMID:24030904

Buried bumper syndrome revisited: a rare but potentially fatal complication of PEG tube placement.

PubMed

Biswas, Saptarshi; Dontukurthy, Sujana; Rosenzweig, Mathew G; Kothuru, Ravi; Abrol, Sunil

2014-01-01

Percutaneous endoscopic gastrostomy (PEG) has been used for providing enteral access to patients who require long-term enteral nutrition for years. Although generally considered safe, PEG tube placement can be associated with many immediate and delayed complications. Buried bumper syndrome (BBS) is one of the uncommon and late complications of percutaneous endoscopic gastrostomy (PEG) placement. It occurs when the internal bumper of the PEG tube erodes into the gastric wall and lodges itself between the gastric wall and skin. This can lead to a variety of additional complications such as wound infection, peritonitis, and necrotizing fasciitis. We present here a case of buried bumper syndrome which caused extensive necrosis of the anterior abdominal wall.

Doxorubicin-loaded micelles based on multiarm star-shaped PLGA-PEG block copolymers: influence of arm numbers on drug delivery.

PubMed

Ma, Guilei; Zhang, Chao; Zhang, Linhua; Sun, Hongfan; Song, Cunxian; Wang, Chun; Kong, Deling

2016-01-01

Star-shaped block copolymers based on poly(D,L-lactide-co-glycolide) (PLGA) and poly(ethylene glycol) (PEG) (st-PLGA-PEG) were synthesized with structural variation on arm numbers in order to investigate the relationship between the arm numbers of st-PLGA-PEG copolymers and their micelle properties. st-PLGA-PEG copolymers with arm numbers 3, 4 and 6 were synthesized by using different cores such as trimethylolpropane, pentaerythritol and dipentaerythritol, and were characterized by nuclear magnetic resonance and gel permeation chromatography. The critical micelle concentration decreased with increasing arm numbers in st-PLGA-PEG copolymers. The doxorubicin-loaded st-PLGA-PEG micelles were prepared by a modified nanoprecipitation method. Micellar properties such as particle size, drug loading content and in vitro drug release behavior were investigated as a function of the number of arms and compared with each other. The doxorubicin-loaded 4-arm PLGA-PEG micelles were found to have the highest cellular uptake efficiency and cytotoxicity compared with 3-arm PLGA-PEG micelles and 6-arm PLGA-PEG micelles. The results suggest that structural tailoring of arm numbers from st-PLGA-PEG copolymers could provide a new strategy for designing drug carriers of high efficiency. Structural tailoring of arm numbers from star shaped-PLGA-PEG copolymers (3-arm/4-arm/6-arm-PLGA-PEG) could provide a new strategy for designing drug carriers of high efficiency.

Nanosized self-emulsifying lipid vesicles of diacylglycerol-PEG lipid conjugates: Biophysical characterization and inclusion of lipophilic dietary supplements

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

Koynova, Rumiana; Tihova, Mariana; Biopharma)

Hydrated diacylglycerol-PEG lipid conjugates, glyceryl dioleate-PEG12 (GDO-PEG12) and glyceryl dipalmitate-PEG23 (GDP-PEG23), spontaneously form uni- or oligolamellar liposomes in their liquid crystalline phase, in distinct difference from the PEGylated phospholipids which form micelles. GDP-PEG23 exhibits peculiar hysteretic phase behavior and can arrange into a long-living hexagonal phase at ambient and physiological temperatures. Liposomes of GDO-PEG12 and its mixture with soy lecithin exchange lipids with the membranes much more actively than common lecithin liposomes; such an active lipid exchange might facilitate the discharging of the liposome cargo upon uptake and internalization, and can thus be important in drug delivery applications. Diacylglycerol-PEG lipidmore » liposome formulations can encapsulate up to 20-30 wt.% lipophilic dietary supplements such as fish oil, coenzyme Q10, and vitamins D and E. The encapsulation is feasible by way of dry mixing, avoiding the use of organic solvent.« less

Pharmacokinetics and in vivo delivery of curcumin by copolymeric mPEG-PCL micelles.

PubMed

Kheiri Manjili, Hamidreza; Ghasemi, Parisa; Malvandi, Hojjat; Mousavi, Mir Sajjad; Attari, Elahe; Danafar, Hossein

2017-07-01

Curcumin (CUR) has been associated with anti-inflammatory, antimicrobial, antioxidant, anti-amyloid, and antitumor effects, but its application is limited because of its low aqueous solubility and poor oral bioavailability. To progress the bioavailability and water solubility of CUR, we synthesized five series of mono methoxy poly (ethylene glycol)-poly (ε-caprolactone) (mPEG-PCL) diblock copolymers. The structure of the copolymers was characterized by H NMR, FTIR, DSC and GPC techniques. In this study, CUR was encapsulated within micelles through a single-step nano-precipitation method, leading to formation of CUR-loaded mPEG-PCL (CUR/mPEG-PCL) micelles. The resulting micelles were characterized further by various techniques such as dynamic light scattering (DLS) and atomic force microscopy (AFM). The cytotoxicity of void CUR, mPEG-PCL and CUR/mPEG-PCL micelles was compared to each other by performing MTT assay of the treated MCF-7 and 4T1 cell line. Study of the in vivo pharmacokinetics of the CUR-loaded micelles was also carried out on selected copolymers in comparison with CUR solution formulations. The results showed that the zeta potential of CUR-loaded micelles was about -11.5mV and the average size was 81.0nm. CUR was encapsulated into mPEG-PCL micelles with loading capacity of 20.65±0.015% and entrapment efficiency of 89.32±0.34%. The plasma AUC (0-t), t 1/2 and C max of CUR micelles were increased by 52.8, 4.63 and 7.51-fold compared to the CUR solution, respectively. In vivo results showed that multiple injections of CUR-loaded micelles could prolong the circulation time and increase the therapeutic efficacy of CUR. These results suggested that mPEG-PCL micelles would be a potential carrier for CUR. Copyright © 2016 Elsevier B.V. All rights reserved.

Near-infrared (1550 nm) in vivo bioimaging based on rare-earth doped ceramic nanophosphors modified with PEG-b-poly(4-vinylbenzylphosphonate)

NASA Astrophysics Data System (ADS)

Kamimura, Masao; Kanayama, Naoki; Tokuzen, Kimikazu; Soga, Kohei; Nagasaki, Yukio

2011-09-01

A novel poly(ethylene glycol) (PEG)-based block copolymer possessing a 4-vinylbenzylphosphonate repeating unit in another segment (PEG-block-poly(4-vinylbenzylphosphonate)) (PEG-b-PVBP) was designed and successfully synthesized. As a control, an end-functionalized PEG possessing a mono-phosphonate group (PEG-PO3H2) was also synthesized. The surface of near-infrared (NIR) phosphors (i.e., ytterbium (Yb) and erbium (Er) ion-codoped Y2O3 nanoparticles (YNPs)) were modified with PEG-b-PVBP (PEG-YNP(b)s) and PEG-PO3H2 (PEG-YNP(1)s). The adsorption of PEG-b-PVBP and PEG-PO3H2 was estimated by Fourier transform infrared (FT-IR) measurements and thermal gravimetric analysis (TGA). The physicochemical characteristics of the obtained YNP samples were analyzed by ζ-potential and dynamic light scattering (DLS) measurements. The ζ-potentials of YNPs modified by these polymers were close to zero, indicating the effective coverage of the YNP surface by our new PEG derivatives. However, the dispersion stability of the PEGylated YNPs was strongly affected by the structure of the PEG terminus. The average diameter of the PEG-YNP(1)s increased, and aggregates precipitated after less than 1 h in phosphate buffer saline (PBS). In contrast, the size did not change at all in the case of PEG-YNP(b)s and the dispersion in PBS was stable for over 1 week. PEG-YNP(b)s also showed high erosion resistance under acidic conditions. The multiple coordinated PVBP segment of the block copolymer on the YNP surface plays a substantial role in improving such dispersion stability. The excellent dispersion stability and strong NIR luminescence of the obtained PEG-YNP(b)s were also confirmed in fetal bovine serum (FBS) solution over 1 week. Furthermore, in vivo NIR imaging of live mice was performed, and the 1550 nm NIR emission of PEG-YNP(b)s from the organ of live mice was confirmed without dissection.A novel poly(ethylene glycol) (PEG)-based block copolymer possessing a 4-vinylbenzylphosphonate

Request for Observations of V405 Peg

NASA Astrophysics Data System (ADS)

Templeton, Matthew R.

2009-12-01

Dr. Axel Schwope (Astrophysikalisches Institut Potsdam) requests time-series monitoring of the magnetic cataclysmic variable V405 Pegasi from 2009 December 28 through 2009 December 30. These observations are requested in support of a planned XMM-Newton observation of V405 Peg on 2009 December 29 beginning at 18:51 UT (JD 2455195.2854) and continuing for 12.5 hours. Observers are asked to provide intensive coverage during the three day window centered on the XMM-Newton observation to provide information on the activity state of V405 Peg, to improve the orbital ephemeris, and to provide optical data that will help constrain the spectral energy distribution of this poorly understood cataclysmic variable. The primary filters for this observation are Johnson B and Cousins I, but all observations will be useful for determining the orbital ephemeris. V405 Peg may show both orbital modulation as well as changes in its activity level. The orbital period is approximately four hours, and observers are asked to obtain at least ten and preferably more data points per cycle in each filter. Please use exposure times that provide S/N of at least 20 in both the comparison and target stars but short exposure times are preferred to detect flickering and other short-timescale variations. Finder charts with sequence may be created using the AAVSO Variable Star Plotter (http://www.aavso.org/vsp). Observations should be submitted to the AAVSO International Database. See full Alert Notice for more details.

Synthesis of linear and cyclic peptide-PEG-lipids for stabilization and targeting of cationic liposome-DNA complexes.

PubMed

Ewert, Kai K; Kotamraju, Venkata Ramana; Majzoub, Ramsey N; Steffes, Victoria M; Wonder, Emily A; Teesalu, Tambet; Ruoslahti, Erkki; Safinya, Cyrus R

2016-03-15

Because nucleic acids (NAs) have immense potential value as therapeutics, the development of safe and effective synthetic NA vectors continues to attract much attention. In vivo applications of NA vectors require stabilized, nanometer-scale particles, but the commonly used approaches of steric stabilization with a polymer coat (e.g., PEGylation; PEG=poly(ethylene glycol)) interfere with attachment to cells, uptake, and endosomal escape. Conjugation of peptides to PEG-lipids can improve cell attachment and uptake for cationic liposome-DNA (CL-DNA) complexes. We present several synthetic approaches to peptide-PEG-lipids and discuss their merits and drawbacks. A lipid-PEG-amine building block served as the common key intermediate in all synthetic routes. Assembling the entire peptide-PEG-lipid by manual solid phase peptide synthesis (employing a lipid-PEG-carboxylic acid) allowed gram-scale synthesis but is mostly applicable to linear peptides connected via their N-terminus. Conjugation via thiol-maleimide or strain-promoted (copper-free) azide-alkyne cycloaddition chemistry is highly amenable to on-demand preparation of peptide-PEG-lipids, and the appropriate PEG-lipid precursors are available in a single chemical step from the lipid-PEG-amine building block. Azide-alkyne cycloaddition is especially suitable for disulfide-bridged peptides such as iRGD (cyclic CRGDKGPDC). Added at 10 mol% of a cationic/neutral lipid mixture, the peptide-PEG-lipids stabilize the size of CL-DNA complexes. They also affect cell attachment and uptake of nanoparticles in a peptide-dependent manner, thereby providing a platform for preparing stabilized, affinity-targeted CL-DNA nanoparticles. Copyright © 2016 Elsevier Ltd. All rights reserved.

P-chlorophenoxyisobutyric acid impairs auxin response for gravity-regulated peg formation in cucumber (Cucumis sativus) seedlings.

PubMed

Shimizu, Minobu; Miyazawa, Yutaka; Fujii, Nobuharu; Takahashi, Hideyuki

2008-01-01

Cucumber (Cucumis sativus L.) seedlings form a specialized protuberance, the peg, on the transition zone between the hypocotyl and the root. When cucumber seeds germinate in a horizontal position, the seedlings develop a peg on the lower side of the transition zone. To verify the role of auxin action in peg formation, we examined the effect of the anti-auxin, p-chlorophenoxyisobutyric acid (PCIB), on peg formation and mRNA accumulation of auxin-regulated genes. Application of PCIB to cucumber seedlings inhibited peg formation. The application of indole-3-acetic acid (IAA) competed with PCIB and induced peg formation. Furthermore, application of PCIB decreased auxin-inducible CsIAA1 mRNA and increased auxin-repressible CsGRP1 mRNA in the lower side of the transition zone. The differential accumulation of CsIAA1 and CsGRP1 mRNAs in the transition zone of cucumber seedlings grown in a horizontal position was smaller in the PCIB-treated seedlings. These results demonstrate that endogenous auxin redistributes and induces the differential expression of auxin-regulated genes, and ultimately results in the suppression or induction of peg formation in the gravistimulated transition zone of cucumber seedlings.

PEG conjugates in clinical development or use as anticancer agents: an overview.

PubMed

Pasut, Gianfranco; Veronese, Francesco M

2009-11-12

During the almost forty years of PEGylation, several antitumour agents, either proteins, peptides or low molecular weight drugs, have been considered for polymer conjugation but only few entered clinical phase studies. The results from the first clinical trials have shared and improved the knowledge on biodistribution, clearance, mechanism of action and stability of a polymer conjugate in vivo. This has helped to design conjugates with improved features. So far, most of the PEG conjugates comprise of a protein, which in the native form has serious shortcomings that limit the full exploitation of its therapeutic action. The main issues can be short in vivo half-life, instability towards degrading enzymes or immunogenicity. PEGylation proved to be effective in shielding sensitive sites at the protein surface, such as antigenic epitopes and enzymatic degradable sequences, as well as in prolonging the drug half-life by decreasing the kidney clearance. In this review PEG conjugates of proteins or low molecular weight drugs, in clinical development or use as anticancer agents, will be taken into consideration. In the case of PEG-protein derivatives the most represented are depleting enzymes, which act by degrading amino acids essential for cancer cells. Interestingly, PEGylated conjugates have been also considered as adjuvant therapy in many standard anticancer protocols, in this regard the case of PEG-G-CSF and PEG-interferons will be presented.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

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

Distribution and clearance of PEG-single-walled carbon nanotube cancer drug delivery vehicles in mice.

PubMed

Bhirde, Ashwin A; Patel, Sachin; Sousa, Alioscka A; Patel, Vyomesh; Molinolo, Alfredo A; Ji, Youngmi; Leapman, Richard D; Gutkind, J Silvio; Rusling, James F

2010-12-01

To study the distribution and clearance of polyethylene glycol (PEG)-ylated single-walled carbon nanotube (SWCNTs) as drug delivery vehicles for the anticancer drug cisplatin in mice. PEG layers were attached to SWCNTs and dispersed in aqueous media and characterized using dynamic light scattering, scanning transmission electron microscopy and Raman spectroscopy. Cytotoxicity was assessed in vitro using Annexin-V assay, and the distribution and clearance pathways in mice were studied by histological staining and Raman spectroscopy. Efficacy of PEG-SWCNT-cisplatin for tumor growth inhibition was studied in mice. PEG-SWCNTs were efficiently dispersed in aqueous media compared with controls, and did not induce apoptosis in vitro. Hematoxylin and eosin staining, and Raman bands for SWCNTs in tissues from several vital organs from mice injected intravenously with nanotube bioconjugates revealed that control SWCNTs were lodged in lung tissue as large aggregates compared with the PEG-SWCNTs, which showed little or no accumulation. Characteristic SWCNT Raman bands in feces revealed the presence of bilary or renal excretion routes. Attachment of cisplatin on bioconjugates was visualized with Z-contrast scanning transmission electron microscopy. PEG-SWCNT-cisplatin with the attached targeting ligand EGF successfully inhibited growth of head and neck tumor xenografts in mice. PEG-SWCNTs, as opposed to control SWCNTs, form more highly dispersed delivery vehicles that, when loaded with both cisplatin and EGF, inhibit growth of squamous cell tumors.

Mitochondria-targeting cyclometalated iridium(III)-PEG complexes with tunable photodynamic activity.

PubMed

Li, Steve Po-Yam; Lau, Chris Tsan-Shing; Louie, Man-Wai; Lam, Yun-Wah; Cheng, Shuk Han; Lo, Kenneth Kam-Wing

2013-10-01

We present a new class of phosphorescent cyclometalated iridium(III) polypyridine poly(ethylene glycol) (PEG) complexes [Ir(N(^)C)2(bpy-CONH-PEG)](PF6) (bpy-CONH-PEG = 4-(N-(2-(ω-methoxypoly-(1-oxapropyl))ethyl)aminocarbonyl)-4'-methyl-2,2'-bipyridine, number average molecular weight (Mn) = 5272.23, weight average molecular weight (Mw) = 5317.38, polydispersity index (PDI) = 1.009; HN(^)C = 2-phenylpyridine, Hppy (1a), 2-((1,1'-biphenyl)-4-yl)pyridine, Hpppy (2a), 2-phenylquinoline, Hpq (3a), 2-phenylbenzothiazole, Hbt (4a), 2-(1-naphthyl)benzothiazole, Hbsn (5a)). The photophysical, photochemical, and biological properties of these complexes have been compared with those of their PEG-free counterparts [Ir(N(^)C)2(bpy-CONH-Et)](PF6) (bpy-CONH-Et = 4-(N-ethylaminocarbonyl)-4'-methyl-2,2'-bipyridine; HN(^)C = Hppy (1b), Hpppy (2b), Hpq (3b), Hbt (4b), Hbsn (5b)). Upon irradiation, all the complexes exhibited intense and long-lived green to orange-red emission under ambient conditions. The emission was phosphorescence in nature and can be quenched by O2 with the generation of singlet oxygen ((1)O2). The quantum yields for (1)O2 production of the complexes in aerated DMSO (0.24-0.83) were found to be dependent on the excited-state lifetimes of the complexes, which can be altered using different cyclometalating ligands (N(^)C). Cell-based assays indicated that the PEG complexes were noncytotoxic in the dark (IC50 > 300 μM); however, most of them became significantly cytotoxic upon irradiation (IC50 = 3.4 - 23.2 μM). Laser-scanning confocal microscopy images revealed localization of complex 3a in the mitochondrial region of HeLa cells and the induction of rapid necrotic cell death upon light activation. Additionally, the lack of dark toxicity and potential application of the PEG complexes as a visualizing reagent have been demonstrated using zebrafish (Danio rerio) as an animal model. Copyright © 2013 Elsevier Ltd. All rights reserved.

Short-Chain PEG Mixed-Monolayer Protected Gold Clusters Increase Clearance and Red Blood Cell Counts

PubMed Central

Simpson, Carrie A.; Agrawal, Amanda C.; Balinski, Andrzej; Harkness, Kellen M.; Cliffel, David E.

2011-01-01

Monolayer-protected gold nanoparticles have great potential as novel building blocks for the design of new drugs and therapeutics based on the easy ability to multifunctionalize them for biological targeting and drug activity. In order to create nanoparticles that are biocompatible in vivo, poly-ethylene glycol functional groups have been added to many previous multifunctionalized particles to eliminate non-specific binding. Recently, monolayer-protected gold nanoparticles with mercaptoglycine functionalities were shown to elicit deleterious effects on the kidney in vivo that were eliminated by incorporating a long-chain, mercapto-undecyl-tetraethylene glycol, at very high loadings into a mixed monolayer. These long-chain PEGs induced an immune response to the particle presumably generating an anti-PEG antibody as seen in other long-chain PEG-ylated nanoparticles in vivo. In the present work, we explore the in vivo effects of high and low percent ratios of a shorter chain, mercapto-tetraethylene glycol, within the monolayer using simple place-exchange reactions. The shorter chain PEG MPCs were expected to have better water solubility due to elimination of the alkyl chain, no toxicity, and long-term circulation in vivo. Shorter chain lengths at lower concentrations should not trigger the immune system into creating an anti-PEG antibody. We found that a 10% molar exchange of this short chain PEG within the monolayer met three of the desired goals: high water solubility, no toxicity, and no immune response as measured by white blood cell counts, but none of the short chain PEG mixed monolayer compositions enabled the nanoparticles to have a long circulation time within the blood as compared to mercapto-undecyl-ethylene glycol, which had a residence time of 4 weeks. We also compared the effects of a hydroxyl versus a carboxylic acid terminal functional group on the end of the PEG thiol on both clearance and immune response. The results indicate that short-chain length

Investigation of PEG crystallization in frozen and freeze-dried PEGylated recombinant human growth hormone-sucrose systems: implications on storage stability.

PubMed

Bhatnagar, Bakul S; Martin, Susan W H; Hodge, Tamara S; Das, Tapan K; Joseph, Liji; Teagarden, Dirk L; Shalaev, Evgenyi Y; Suryanarayanan, Raj

2011-08-01

The objectives of the current study were to investigate (i) the phase behavior of a PEGylated recombinant human growth hormone (PEG-rhGH, ∼60 kDa) during freeze-drying and (ii) its storage stability. The phase transitions during freeze-thawing of an aqueous solution containing PEG-rhGH and sucrose were characterized by differential scanning calorimetry. Finally, PEG-rhGH and sucrose formulations containing low, medium, and high polyethylene glycol (PEG) to sucrose ratios were freeze-dried in dual-chamber syringes and stored at 4°C and 25°C. Chemical decomposition (methionine oxidation and deamidation) and irreversible aggregation were characterized by size-exclusion and ion-exchange chromatography, and tryptic mapping. PEG crystallization was facilitated when it was covalently linked with rhGH. When the solutions were frozen, phase separation into PEG-rich and sucrose-rich phases facilitated PEG crystallization and the freeze-dried cake contained crystalline PEG. Annealing caused PEG crystallization and when coupled with higher drying temperatures, the primary drying time decreased by up to 51%. When the freeze-dried cakes were stored at 4°C, while there was no change in the purity of the PEG-rhGH monomer, deamidation was highest in the formulations with the lowest PEG to sucrose ratio. When stored at 25°C, this composition also showed the most pronounced decrease in monomer purity, the highest level of aggregation, and deamidation. Furthermore, an increase in PEG crystallinity during storage was accompanied by a decrease in PEG-rhGH stability. Interestingly, during storage, there was no change in PEG crystallinity in formulations with medium and high PEG to sucrose ratios. Although PEG crystallization during freeze-drying did not cause protein degradation, crystallization during storage might have influenced protein stability. Copyright © 2011 Wiley-Liss, Inc.

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

PubMed

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

2017-05-01

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

Suitability of polymer materials for production of pulmonary microparticles using a PGSS supercritical fluid technique: thermodynamic behaviour of fatty acids, PEGs and PEG-fatty acids.

PubMed

Vijayaraghavan, Meera; Stolnik, Snjezana; Howdle, Steven M; Illum, Lisbeth

2012-11-15

The thermodynamic behaviour of selected polymeric components for preparation of controlled release microparticles using supercritical carbon dioxide (scCO(2)) processing was investigated. The polymeric materials selected were egg lecithin (a model for the lung surfactant phospholipid), poly(ethyleneglycol) (PEG) of different molecular weights, fatty acids (C18, C16, and C14), and physical blends of PEGs and fatty acids. In addition a range of PEG-stearates was also assessed. Analysis of thermodynamic behaviour was performed by differential scanning calorimetry (DSC) and by assessment of their interaction with scCO(2) in a high-pressure variable volume view cell. The key criterion was to demonstrate a strong interaction with scCO(2) and to show liquefaction of the polymeric material at acceptable processing temperatures and pressures. Positive results should then indicate the suitability of these materials for processing by the Particle from Gas Saturated Solutions (PGSS) technique using scCO(2) to create microparticles for pulmonary administration. It was found that the materials tested interacted with scCO(2) and showed a sufficient lowering of their melting temperature (T(m)) to make them suitable for use in the PGSS microparticle production rig. Fatty acids of low T(m) were shown to act as a plasticising agent and to lower the T(m) of PEG further during interaction with scCO(2). Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of Laser Etching on the Corrosion Susceptibility of SAVY 4000 and Hagan Containers

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

Hyer, Holden Christopher; Duque, Juan; Smith, Paul Herrick

Since the late 1990’s, the Hagan container was used as the primary container for packaging of plutonium-bearing materials. The Hagan design consisted of a threaded closure, a Viton® ORing, a carbon-carbon filter, and a 304L stainless steel (SS) body. Over the years, Hagans have shown vulnerability in their design [1]. In 2008, The Department of Energy (DOE) issued DOE M 441.1-1, Nuclear Material Packaging Manual, which detailed an approach to obtain highconfidence in containers by including specific design requirements, material contents and an approach to determine life span from said contents, and surveillance techniques [2]. In response to both themore » vulnerability issues with the Hagan and DOE M 441.1-1, the SAVY 4000 container with its twist style closure, Viton® O-Ring, Fiberfrax-Gortex filter, and annealed 316L SS body, was designed as the replacement for Hagan containers, but only for a short term lifespan of 5 years [1]. However, both the Hagan and SAVY 4000 are being pushed to maintain a lifespan of 40 years. Therefore, proper confidence must be placed on each component of each container to last a minimum of 40 years. So far, the biggest concern found during surveillance of these containers is corrosion and the potential for failure by corrosion. One concern is that the containers fail due to stress corrosion cracking (SCC), especially around the weld between the collar and the body as welds leave residual stresses. One advantage the SAVY 4000 has is that the body is annealed, but its weld is still susceptible as it was welded after annealing [3, 4]. Moreover, 316L SS is known to have a higher pitting resistance (pits are a precursor to SCC and can also lead to extensive failure of the material), than 304L SS [4]. During recent surveillance activities, two SAVY 4000’s containing Solution Assay Instrument (SAI) solutions were opened. The SAI SAVY 4000’s contained plutonium (Pu) in 3M HCl solution in plastic volumetric flasks placed inside of

PEG-PLA-PEG block copolymeric nanoparticles for oral immunization against hepatitis B.

PubMed

Jain, Arvind K; Goyal, Amit K; Mishra, Neeraj; Vaidya, Bhuvaneshwar; Mangal, Sharad; Vyas, Suresh P

2010-03-15

PLA/PLGA nanoparticles are well known as efficient vaccine delivery systems, but they have got limitation in oral vaccine delivery because of their sensitivity to harsh gastric environment. The aim of present study was to improve the stability of PLA nanoparticles in such environment by copolymerizing PLA with PEG. Nanoparticles were formulated using different block copolymers AB, ABA and BAB (where 'A' is PLA and 'B' is PEG) encapsulating hepatitis B surface antigen (HBsAg) to evaluate their efficacy as oral vaccine delivery system. The results of in vitro studies engrave the efficiency of copolymeric nanoparticles to retain encapsulated antigen and average particle size even after 2 h incubation in simulated gastric fluid and simulated intestinal fluid. Fluorescence microscopic studies indicated efficient uptake of copolymeric nanoparticles by gut mucosa of immunized mice model as compared to control. Finally copolymeric and PLA nanoparticles, encapsulating HBsAg, were evaluated for their adjuvancity in generating immune response after oral administration. PLA nanoparticles could not generate an effective immune response due to stability issues. On the other hand, oral administration of copolymeric nanoparticles exhibited effective levels of humoral immunity along with the mucosal (sIgA) and cellular immune response (T(H)1). The results of in vitro and in vivo studies demonstrate that BAB nanoparticles depict enhanced mucosal uptake leading to effective immune response as compared to other copolymeric nanoparticles. Present study indicates the efficacy of BAB nanoparticles as a promising carrier for oral immunization. 2009 Elsevier B.V. All rights reserved.

Study of SiRNA-loaded PS-mPEG/CaP nanospheres on lung cancer

NASA Astrophysics Data System (ADS)

Wang, Qi; Qin, Liubin; Sun, Ying; Shen, Ming; Duan, Yourong

2014-05-01

An ultrasound-adsorption method was used to prepare Bcl-2-SiRNA-loaded PS-mPEG/CaP nanospheres. The size and zeta potential were 18.41 ± 4.31 nm ( n = 5) and -23.5 ± 0.6 mV, respectively. The entrapment efficiency of SiRNA was 92.86 %. MTT assay results confirmed that the blank nanospheres demonstrated a negligible cytotoxicity response in H1299 cells. Flow cytometer analysis results demonstrated that PS-mPEG/CaP NSs could carry SiRNA into the cells effectively. RT-PCR experiments and apoptosis assay results approved that, compared with free SiRNA, SiRNA-loaded PS-mPEG/CaP NSs could silence Bcl-2 gene and induce cell apoptosis effectively. In vivo distribution results confirmed PS-mPEG/CaP NSs could carry SiRNA enter the tumor tissue effectively. Taken together, these results suggest that the Bcl-2-SiRNA-loaded PS-mPEG/CaP nanospheres have great potential to be used to cure lung cancer.

Test and Evaluation Report of the IVAC (Trademark) Vital Check Monitor Model 4000AEE

DTIC Science & Technology

1992-02-01

AD-A248 834 111111 jIf+l l’ l USAARL Report No. 92-14 Test and Evaluation Report of the IVAC® Vital Check Monitor DTI ~cModel 4000AEE f ELECTE APR17...does not constitute an official Department of the Army endorsement or approval of the use ot such commercial items. Reviewed: DENNIS F . SHANAHAN LTC, MC...to 12.4 GHz) was scanned for emissions. The IVACO Model 4000AEE was operated with both ac and battery power. 2.10.3.2 The radiated susceptibility

Cholesterol-PEG comodified poly (N-butyl) cyanoacrylate nanoparticles for brain delivery: in vitro and in vivo evaluations.

PubMed

Hu, Xiao; Yang, Feifei; Liao, Yonghong; Li, Lin; Zhang, Lan

2017-11-01

This study investigated cholesterol-polyethylene glycol (PEG) comodified poly (ethyleneglycol)-poly (lactide) nanoparticles (CLS-PEG NPs) as a novel, biodegradable brain drug delivery system and included an evaluation of its in vitro and in vivo properties. To this end, coumarin-6 (C6), a fluorescent probe, was encapsulated into CLS-PEG NPs by an emulsion polymerization method. We reported that the use of CLS-PEG NPs led to a sustained drug release in vitro. Additionally, cell viability experiments confirmed their safety. The uptake and transport of CLS-PEG NPs, by bEnd.3 cells (an immortalized mouse brain endothelial cell line), was significantly higher than that of a control C6 solution. An investigation of the uptake mechanisms of different NP formulations demonstrated that cholesterol modifications may be the primary way to improve the efficiency of cellular uptake, wherein macropinocytosis may be the most important endocytic pathway in this process. An investigation of the transport mechanisms of CLS-PEG NPs also implicated macropinocytosis, energy and cholesterol in bEnd.3 cells lines. Following an intravenous (IV) administration to rats, pharmacokinetic experiments indicated that C6-loaded CLS-PEG NPs achieved sustained release for up to 12 h. In addition, IV delivery of CLS-PEG NPs appeared to significantly improve the ability of C6 to pass through the blood-brain barrier: the concentration of C6 found in the brain increased nearly 14.2-fold when C6 CLS-PEG NPs were used rather than a C6 solution. These in vitro and in vivo results strongly suggest that CLS-PEG NPs are a promising drug delivery system for targeting the brain, with low toxicity.

Development and Validation of a New Near-Infrared Sensor to Measure Polyethylene Glycol (PEG) Concentration in Water.

PubMed

Buzzi, Olivier; Yuan, Shengyang; Routley, Benjamin

2017-06-10

A near-infrared absorption based laser sensor has been designed and validated for the real-time measurement of polyethylene glycol (PEG) concentration. The wavelength was selected after the determination of the absorption spectrum of deionised water and PEG solutions using a Varian Cary 6000i spectrophotometer, in order to limit the influence of PEG molecular mass on the absorption measurement. With this new sensor, the water is treated as the attenuating species and the addition of PEG in water reduces the absorbance of the medium. The concept was validated using three different PEG types (PEG 6,000, 20,000, and 35,000) and it was found that the results follow Beer Lambert's law. The influence of temperature was assessed by testing the PEG 20,000 at four different temperatures that could be encountered in a laboratory environment. The data show a slight temperature influence (increase of absorbance by 8% when the temperature rises from about 20 to about 29 degrees). Following the validation phase conducted ex situ, a prototype of an immersible sensor was built and calibrated for in situ measurements.

Influence of PEG coating on the oral bioavailability of gold nanoparticles in rats.

PubMed

Alalaiwe, Ahmed; Roberts, Georgia; Carpinone, Paul; Munson, John; Roberts, Stephen

2017-11-01

Metallic nanoparticles can be produced in a variety of shapes, sizes, and surface chemistries, making them promising potential tools for drug delivery. Most studies to date have evaluated uptake of metallic nanoparticles from the GI tract with methods that are at best semi-quantitative. This study used the classical method of comparing blood concentration area under the curve (AUC) following intravenous and oral doses to determine the oral bioavailability of 1, 2 and 5 kDa PEG-coated 5 nm gold nanoparticles (AuNPs). Male rats were given a single intravenous dose (0.8 mg/kg) or oral (gavage) dose (8 mg/kg) of a PEG-coated AuNP, and the concentration of gold was measured in blood over time and in tissues (liver, spleen and kidney) at sacrifice. Blood concentrations following oral administration were inversely related to PEG size, and the AUC in blood was significantly greater for the 1 kDa PEG-coated AuNPs than particles coated with 2 or 5 kDa PEG. However, bioavailabilities of all of the particles were very low (< 0.1%). Concentrations in liver, spleen and kidney were similar after the intravenous doses, but kidney showed the highest concentrations after an oral dose. In addition to providing information on the bioavailability of AuNPs coated with PEG in the 1-5 kDa range, this study demonstrates the utility of applying the blood AUC approach to assess the quantitative oral bioavailability of metallic nanoparticles.

Volumetric Properties, Viscosities, and Refractive Indices of the Binary Systems 1-Butanol + PEG 200, + PEG 400, and + TEGDME

NASA Astrophysics Data System (ADS)

Živković, N.; Šerbanović, S.; Kijevčanin, M.; Živković, E.

2013-06-01

Densities, viscosities, and refractive indices of three binary systems consisting of 1-butanol with polyethylene glycols of different molecular weights (PEG 200 and PEG 400) or tetraethylene glycol dimethyl ether (TEGDME) were measured at ten temperatures (288.15, 293.15, 298.15, 303.15, 308.15, 313.15, 318.15, 323.15, 328.15, and 333.15) K and atmospheric pressure. Densities of the selected binary mixtures were measured with an Anton Paar DMA 5000 digital vibrating U-tube densimeter, refractive indices were measured with an automatic Anton Paar RXA-156 refractometer, while for viscosity measurements, a digital Stabinger SVM 3000/G2 viscometer was used. From these data, excess molar volumes were calculated and fitted to the Redlich-Kister equation. The obtained results have been analyzed in terms of specific molecular interactions and mixing behavior between mixture components, as well as the influence of temperature on them. Viscosity data were also correlated by Grunberg-Nissan, Eyring-UNIQUAC, three-body McAlister, and Eyring-NRTL models.

A mPEG-PLGA-b-PLL copolymer carrier for adriamycin and siRNA delivery.

PubMed

Liu, Peifeng; Yu, Hui; Sun, Ying; Zhu, Mingjie; Duan, Yourong

2012-06-01

A amphiphilic block copolymer composed of conventional monomethoxy (polyethylene glycol)-poly (d,l-lactide-co-glycolide)-poly (l-lysine) (mPEG-PLGA-b-PLL) was synthesized. The chemical structure of this copolymer and its precursors was confirmed by Fourier Transform Infrared Spectroscopy (FTIR), (1)H Nuclear Magnetic Resonance ((1)H NMR) and Gel Permeation Chromatography (GPC). The copolymer was used to prepare nanoparticles (NPs) that were then loaded with either the anti-cancer drug adriamycin or small interfering RNA-negative (siRNA) using a double emulsion method. MTT assays used to study the in vitro cytotoxicity of mPEG-PLGA-b-PLL NPs showed that these particles were not toxic in huh-7 hepatic carcinoma cells. Confocal laser scanning microscopy (CLSM) and flow cytometer analysis results demonstrated efficient mPEG-PLGA-b-PLL NPs-mediated delivery of both adriamycin and siRNA into the cells. In vivo the targeting delivery of adriamycin or siRNA mediated by mPEG-PLGA-b-PLL NPs in the huh-7 hepatic carcinoma-bearing mice was evaluated using a fluorescence imaging system. The targeting delivery results and froze section analysis confirmed that drug or siRNA is deliver to tumor more efficiently by mPEG-PLGA-b-PLL NPs than free drug or Lipofectamine™2000. The high efficiency delivery of mPEG-PLGA-b-PLL NPs mainly due to the enhancement of cellular uptake. These results imply that mPEG-PLGA-b-PLL NPs have a great potential to be used as an effective carriers for adriamycin or siRNA. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Dissolution enhancement of chlorzoxazone using cogrinding technique

PubMed Central

Raval, Mihir K.; Patel, Jaydeep M.; Parikh, Rajesh K.; Sheth, Navin R.

2015-01-01

Purpose: The aim of the present work was to improve rate of dissolution and processing parameters of BCS class II drug, chlorzoxazone using cogrinding technique in the presence of different excipients as a carrier. Materials and Methods: The drug was coground with various carriers like polyethylene glycol (PEG 4000), hydroxypropyl methylcellulose (HPMC) E50LV, polyvinylpyrrolidone (PVP)K30, Kaolin and Neusilin US2 using ball mill, where only PEG 4000 improved dissolution rate of drug by bringing amorphization in 1:3 ratio. The coground mixture after 3 and 6 h was evaluated for various analytical, physicochemical and mechanical parameters. Results: The analysis showed conversion of Chlorzoxazone from its crystalline to amorphization form upon grinding with PEG 4000. Coground mixture as well as its directly compressed tablet showed 2.5-fold increment in the dissolution rate compared with pure drug. Directly compressible tablets prepared from pure drug required a large quantity of microcrystalline cellulose (MCC) during compression. The coground mixture and formulation was found stable in nature even after storage (40°C/75% relative humidity). Conclusions: Cogrinding can be successfully utilized to improve the rate of dissolution of poorly water soluble drugs and hence bioavailability. PMID:26682195

A Functional Iron Oxide Nanoparticles Modified with PLA-PEG-DG as Tumor-Targeted MRI Contrast Agent.

PubMed

Xiong, Fei; Hu, Ke; Yu, Haoli; Zhou, Lijun; Song, Lina; Zhang, Yu; Shan, Xiuhong; Liu, Jianping; Gu, Ning

2017-08-01

Tumor targeting could greatly promote the performance of magnetic nanomaterials as MRI (Magnetic Resonance Imaging) agent for tumor diagnosis. Herein, we reported a novel magnetic nanoparticle modified with PLA (poly lactic acid)-PEG (polyethylene glycol)-DG (D-glucosamine) as Tumor-targeted MRI Contrast Agent. In this work, we took use of the D-glucose passive targeting on tumor cells, combining it on PLA-PEG through amide reaction, and then wrapped the PLA-PEG-DG up to the Fe 3 O 4 @OA NPs. The stability and anti phagocytosis of Fe 3 O 4 @OA@PLA-PEG-DG was tested in vitro; the MRI efficiency and toxicity was also detected in vivo. These functional magnetic nanoparticles demonstrated good biocompatibility and stability both in vitro and in vivo. Cell experiments showed that Fe 3 O 4 @OA@PLA-PEG-DG nanoparticles exist good anti phagocytosis and high targetability. In vivo MRI images showed that the contrast effect of Fe 3 O 4 @OA@PLA-PEG-DG nanoparticles prevailed over the commercial non tumor-targeting magnetic nanomaterials MRI agent at a relatively low dose. The DG can validly enhance the tumor-targetting effect of Fe 3 O 4 @OA@PLA-PEG nanoparticle. Maybe MRI agents with DG can hold promise as tumor-targetting development in the future.

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

PubMed

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

2015-04-01

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

Characterization and tribology of PEG-like coatings on UHMWPE for total hip replacements.

PubMed

Kane, Sheryl R; Ashby, Paul D; Pruitt, Lisa A

2010-03-15

A crosslinked hydrogel coating similar to poly(ethylene glycol) (PEG) was covalently bonded to the surface of ultrahigh molecular weight polyethylene (UHMWPE) to improve the lubricity and wear resistance of the UHWMPE for use in total joint replacements. The chemistry, hydrophilicity, and protein adsorption resistance of the coatings were determined, and the wear behavior of the PEG-like coating was examined by two methods: pin-on-disk tribometry to evaluate macroscale behavior, and atomic force microscopy (AFM) to simulate asperity wear. As expected, the coating was found to be highly PEG-like, with approximately 83% ether content by x-ray photoelectron spectroscopy and more hydrophilic and resistant to protein adsorption than uncoated UHMWPE. Pin-on-disk testing showed that the PEG-like coating could survive 3 MPa of contact pressure, comparable to that experienced by total hip replacements. AFM nanoscratching experiments uncovered three damage mechanisms for the coatings: adhesion/microfracture, pure adhesion, and delamination. The latter two mechanisms appear to correlate well with wear patterns induced by pin-on-disk testing and evaluated by attenuated total reflection Fourier transform infrared spectroscopy mapping. Understanding the mechanisms by which the PEG-like coatings wear is critical for improving the behavior of subsequent generations of wear-resistant hydrogel coatings. (c) 2009 Wiley Periodicals, Inc.

The application of polyethylene glycol (PEG) to electron microscopy

PubMed Central

1980-01-01

The cytoplasm of cells from a variety of tissues has been viewed in sections (0.25-1 micrometers) devoid of any embedding resin. Glutaraldehyde- and osmium tetroxide-fixed tissues were infiltrated and embedded in a water-miscible wax, polyethylene glycol (PEG), and subsequently sectioned on dry glass or diamond knives. The PEG matrix was removed and the sections were placed on Formvarcarbon-polylysine- coated grids, dehydrated, dried by the critical-point method, and observed in either the high- or low-voltage electron microscope. Stereoscopic views of cells devoid of embedding resin present an image of cell utrastructure unobscured by electron-scattering resins similar to the image of whole, unembedded critical-point-dried or freeze-dried cultured cells observed by transmission electron microscopy. All organelles, including the cytoskeletal structures, are identified and appear not to have been damaged during processing, although membrane components appear somewhat less distinct. The absence of an embedding matrix eliminates the need for additional staining to increase contrast, unlike the situation with specimens embedded in standard electron-scattering resins. The PEG technique thus appears to be a valuable adjunct to conventional methods for ultrastructural analysis. PMID:7400222

The application of polyethylene glycol (PEG) to electron microscopy.

PubMed

Wolosewick, J J

1980-08-01

The cytoplasm of cells from a variety of tissues has been viewed in sections (0.25-1 micrometers) devoid of any embedding resin. Glutaraldehyde- and osmium tetroxide-fixed tissues were infiltrated and embedded in a water-miscible wax, polyethylene glycol (PEG), and subsequently sectioned on dry glass or diamond knives. The PEG matrix was removed and the sections were placed on Formvarcarbon-polylysine-coated grids, dehydrated, dried by the critical-point method, and observed in either the high- or low-voltage electron microscope. Stereoscopic views of cells devoid of embedding resin present an image of cell utrastructure unobscured by electron-scattering resins similar to the image of whole, unembedded critical-point-dried or freeze-dried cultured cells observed by transmission electron microscopy. All organelles, including the cytoskeletal structures, are identified and appear not to have been damaged during processing, although membrane components appear somewhat less distinct. The absence of an embedding matrix eliminates the need for additional staining to increase contrast, unlike the situation with specimens embedded in standard electron-scattering resins. The PEG technique thus appears to be a valuable adjunct to conventional methods for ultrastructural analysis.

Effects of bevacizumab loaded PEG-PCL-PEG hydrogel intracameral application on intraocular pressure after glaucoma filtration surgery.

PubMed

Han, Qian; Wang, Yuqi; Li, Xiabin; Peng, Ribo; Li, Ailing; Qian, Zhiyong; Yu, Ling

2015-08-01

PEG-PCL-PEG (PECE) hydrogel for intracameral injection as a sustained delivery system can get a stable release of the medication and achieve an effective local concentration. The injectable PECE hydrogel is thermosensitive nano-material which is flowing sol at low temperature and can shift to nonflowing gel at body temperature. This study evaluated the intracameral injection of bevacizumab combined with a PECE hydrogel drug release system on postoperative scarring and bleb survival after experimental glaucoma filtration surgery. The best result was achieved in the bevacizumab loaded PECE hydrogels group, which presented the lowest IOP values after surgery. And the blebs were significantly more persistent in this group. Histology, Massion trichrome staining and immunohistochemistry further demonstrated that glaucoma filtration surgery in combination with bevacizumab loaded PECE hydrogel resulted in good bleb survival due to scar formation inhibition. In conclusions, this study demonstrated that bevacizumab-loaded PECE hydrogel for intracameral injection as a sustained delivery system provide a great opportunity to increase the therapeutic efficacy of glaucoma filtration surgery.

Inert Reassessment Document for PEG Fatty Acid Esters

EPA Pesticide Factsheets

The tolerance reassessment decision document and action memorandum for the PEG fatty acid ester date September 28, 2005, included two tolerance exemptions (under 40 CFR 180.910 and $) CFR 180.930, respectively)

A PEG-Based Hydrogel for Effective Wound Care Management

PubMed Central

Chen, Sen-Lu; Fu, Ru-Huei; Liao, Shih-Fei; Liu, Shih-Ping; Lin, Shinn-Zong; Wang, Yu-Chi

2018-01-01

It is extremely challenging to achieve strong adhesion in soft tissues while minimizing toxicity, tissue damage, and other side effects caused by wound sealing materials. In this study, flexible synthetic hydrogel sealants were prepared based on polyethylene glycol (PEG) materials. PEG is a synthetic material that is nontoxic and inert and, thus, suitable for use in medical products. We evaluated the in vitro biocompatibility tests of the dressings to assess cytotoxicity and irritation, sensitization, pyrogen toxicity, and systemic toxicity following the International Organization for Standardization 10993 standards and the in vivo effects of the hydrogel samples using Coloskin liquid bandages as control samples for potential in wound closure. PMID:29637814

Near-infrared (1550 nm) in vivo bioimaging based on rare-earth doped ceramic nanophosphors modified with PEG-b-poly(4-vinylbenzylphosphonate).

PubMed

Kamimura, Masao; Kanayama, Naoki; Tokuzen, Kimikazu; Soga, Kohei; Nagasaki, Yukio

2011-09-01

A novel poly(ethylene glycol) (PEG)-based block copolymer possessing a 4-vinylbenzylphosphonate repeating unit in another segment (PEG-block-poly(4-vinylbenzylphosphonate)) (PEG-b-PVBP) was designed and successfully synthesized. As a control, an end-functionalized PEG possessing a mono-phosphonate group (PEG-PO(3)H(2)) was also synthesized. The surface of near-infrared (NIR) phosphors (i.e., ytterbium (Yb) and erbium (Er) ion-codoped Y(2)O(3) nanoparticles (YNPs)) were modified with PEG-b-PVBP (PEG-YNP(b)s) and PEG-PO(3)H(2) (PEG-YNP(1)s). The adsorption of PEG-b-PVBP and PEG-PO(3)H(2) was estimated by Fourier transform infrared (FT-IR) measurements and thermal gravimetric analysis (TGA). The physicochemical characteristics of the obtained YNP samples were analyzed by ζ-potential and dynamic light scattering (DLS) measurements. The ζ-potentials of YNPs modified by these polymers were close to zero, indicating the effective coverage of the YNP surface by our new PEG derivatives. However, the dispersion stability of the PEGylated YNPs was strongly affected by the structure of the PEG terminus. The average diameter of the PEG-YNP(1)s increased, and aggregates precipitated after less than 1 h in phosphate buffer saline (PBS). In contrast, the size did not change at all in the case of PEG-YNP(b)s and the dispersion in PBS was stable for over 1 week. PEG-YNP(b)s also showed high erosion resistance under acidic conditions. The multiple coordinated PVBP segment of the block copolymer on the YNP surface plays a substantial role in improving such dispersion stability. The excellent dispersion stability and strong NIR luminescence of the obtained PEG-YNP(b)s were also confirmed in fetal bovine serum (FBS) solution over 1 week. Furthermore, in vivo NIR imaging of live mice was performed, and the 1550 nm NIR emission of PEG-YNP(b)s from the organ of live mice was confirmed without dissection.

Measuring intestinal fluid transport in vitro: Gravimetric method versus non-absorbable marker.

PubMed

Whittamore, Jonathan M; Genz, Janet; Grosell, Martin; Wilson, Rod W

2016-04-01

The gut sac is a long-standing, widely used in vitro preparation for studying solute and water transport, and calculation of these fluxes requires an accurate assessment of volume. This is commonly determined gravimetrically by measuring the change in mass over time. While convenient this likely under-estimates actual net water flux (Jv) due to tissue edema. We evaluated whether the popular in vivo volume marker [(14)C]-PEG 4000, offers a more representative measure of Jvin vitro. We directly compared these two methods in five teleost species (toadfish, flounder, rainbow trout, killifish and tilapia). Net fluid absorption by the toadfish intestine based on PEG was significantly higher, by almost 4-fold, compared to gravimetric measurements, compatible with the latter under-estimating Jv. Despite this, PEG proved inconsistent for all of the other species frequently resulting in calculation of net secretion, in contrast to absorption seen gravimetrically. Such poor parallelism could not be explained by the absorption of [(14)C]-PEG (typically <1%). We identified a number of factors impacting the effectiveness of PEG. One was adsorption to the surface of sample tubes. While it was possible to circumvent this using unlabelled PEG 4000, this had a deleterious effect on PEG-based Jv. We also found sequestration of PEG within the intestinal mucus. In conclusion, the short-comings associated with the accurate representation of Jv by gut sac preparations are not overcome by [(14)C]-PEG. The gravimetric method therefore remains the most reliable measure of Jv and we urge caution in the use of PEG as a volume marker. Copyright © 2016 Elsevier Inc. All rights reserved.

E-selectin-targeted Sialic Acid-PEG-dexamethasone Micelles for Enhanced Anti-Inflammatory Efficacy for Acute Kidney Injury.

PubMed

Hu, Jing-Bo; Kang, Xu-Qi; Liang, Jing; Wang, Xiao-Juan; Xu, Xiao-Ling; Yang, Ping; Ying, Xiao-Ying; Jiang, Sai-Ping; Du, Yong-Zhong

2017-01-01

The effective treatment for acute kidney injury (AKI) is currently limited, and care is primarily supportive. Sialic acid (SA) is main component of Sialyl Lewis x antigen on the mammalian cell surface, which participates in E-selectin binding. Therefore, dexamethasone(DXM)-loaded E-selectin-targeting sialic acid-polyethylene glycol-dexamethasone (SA-PEG-DXM/DXM) conjugate micelles are designed for ameliorating AKI. The conjugates are synthesized via the esterification reaction between PEG and SA or DXM, and can spontaneously form micelles in an aqueous solution with a 65.6 µg/mL critical micelle concentration. Free DXM is incorporated into the micelles with 6.28 ± 0.21% drug loading content. In vitro DXM release from SA-PEG-DXM/DXM micelles can be prolonged to 48h. Much more SA-PEG-DXM micelles can be internalized by lipopolysaccharide (LPS)-activated human umbilical vein endothelial cells (HUVECs) in comparison to PEG-DXM micelles due to specific interaction between SA and E-selectin expressed on HUVECs, and consequently more SA-PEG-DXM micelles are accumulated in the kidney of AKI murine model. Furthermore, SA in SA-PEG-DXM conjugates can significantly ameliorate LPS-induced production of pro-inflammatory cytokines via suppressing LPS-activated Beclin-1/Atg5-Atg12-mediated autophagy to attenuate toxicity. Compared with free DXM and PEG-DXM/DXM micelles, SA-PEG-DXM/DXM micelles show better therapeutical effects, as reflected by the improved renal function, histopathological changes, pro-inflammatory cytokines, oxidative stress and expression of apoptotic related proteins.

Photoinduced PEG deshielding from ROS-sensitive linkage-bridged block copolymer-based nanocarriers for on-demand drug delivery.

PubMed

Li, Jie; Sun, Chunyang; Tao, Wei; Cao, Ziyang; Qian, Haisheng; Yang, Xianzhu; Wang, Jun

2018-07-01

Controlling poly(ethylene glycol) (PEG) shielding/deshielding at the desired site of action exhibits great advantages for nanocarrier-based on-demand drug delivery in vivo. However, the current PEG deshielding strategies were mainly designed for anticancer drug delivery; even so, their applications are also limited by tumor heterogeneity. As a proof-of-concept, we explored a photoinduced PEG deshielding nanocarrier TK-NP Ce6&PTX to circumvent the aforementioned challenge. The TK-NP Ce6&PTX encapsulating chlorin e6 (Ce6) and paclitaxel (PTX) was self-assembled from an innovative thioketal (TK) linkage-bridged diblock copolymer of PEG with poly(d,l-lactic acid) (PEG-TK-PLA). We demonstrated that the high PEGylation of TK-NP Ce6&PTX in blood helps the nanocarrier efficiently avoid rapid clearance and consequently prolongs its circulation time. At the desired site (tumor), 660-nm red light irradiation led to ROS generation in situ, which readily cleaved the TK linkage, resulting in PEG deshielding. Such photoinduced PEG deshielding at the desired site significantly enhances the cellular uptake of the nanocarriers, achieving on-demand drug delivery and superior therapeutic efficacy. More importantly, this strategy of photoinducing PEG deshielding of nanocarriers could potentially extend to a variety of therapeutic agents beyond anticancer drugs for on-demand delivery. Copyright © 2018 Elsevier Ltd. All rights reserved.

In situ formation of leak-free polyethylene glycol (PEG) membranes in microfluidic fuel cells.

PubMed

Ho, W F; Lim, K M; Yang, K-L

2016-11-29

Membraneless microfluidic fuel cells operated under two co-laminar flows often face serious fuel cross-over problems, especially when flow rates are close to zero. In this study, we show that polyethylene glycol (PEG) monomers can be cross-linked inside microfluidic channels to form leak-free PEG membranes, which prevent mixing of two incompatible electrolyte solutions while allowing diffusion of certain molecules (e.g. glucose) and ions. By using PEG monomers of different molecular weights and cross-linking conditions, we are able to tailor selectivity of the membrane to allow passage of glucose while blocking larger molecules such as trypan blue. As a proof of principle, a microfluidic fuel cell with a PEG membrane and two incompatible electrolytes (acid and base) is demonstrated. Thanks to the leak-free nature of the PEG membrane, these two electrolytes do not mix together even at very slow flow rates. This microfluidic fuel cell is able to generate a voltage up to ∼450 mV from 10 mM of glucose with a flow rate of 20 μL min -1 . This microfluidic fuel cell is potentially useful as a miniature power source for many applications.

Photo-crosslinked PDMSstar-PEG Hydrogels: Synthesis, Characterization, and Potential Application for Tissue Engineering Scaffolds

PubMed Central

Hou, Yaping; Schoener, Cody A.; Regan, Katherine R.; Munoz-Pinto, Dany; Hahn, Mariah S.; Grunlan, Melissa A.

2010-01-01

Inorganic-organic hydrogels with tunable chemical and physical properties were prepared from methacrylated star polydimethylsiloxane (PDMSstar-MA) and diacrylated poly(ethylene glycol) (PEG-DA) for use as tissue engineering scaffolds. Eighteen compositionally unique hydrogels were prepared by photo-crosslinking varying weight ratios of PEG-DA and PDMSstar-MA of different molecular weights (Mn): PEG-DA (Mn = 3.4k and 6k g/mol) and PDMSstar-MA (Mn = 1.8k, 5k and 7k g/mol). Introduction of PDMSstar-MA caused formation of discrete PDMS-enriched microparticles dispersed within the PEG matrix. The swelling ratio, mechanical properties in tension and compression, non-specific protein adhesion, controlled introduction of bioactivity and cytotoxicity of hydrogels were studied. This library of inorganic-organic hydrogels with tunable properties provides a useful platform to study the effect of scaffold properties on cell behavior. PMID:20146518

Foreign Body Response to Intracortical Microelectrodes Is Not Altered with Dip-Coating of Polyethylene Glycol (PEG)

PubMed Central

Lee, Heui C.; Gaire, Janak; Currlin, Seth W.; McDermott, Matthew D.; Park, Kinam; Otto, Kevin J.

2017-01-01

Poly(ethylene glycol) (PEG) is a frequently used polymer for neural implants due to its biocompatible property. As a follow-up to our recent study that used PEG for stiffening flexible neural probes, we have evaluated the biological implications of using devices dip-coated with PEG for chronic neural implants. Mice (wild-type and CX3CR1-GFP) received bilateral implants within the sensorimotor cortex, one hemisphere with a PEG-coated probe and the other with a non-coated probe for 4 weeks. Quantitative analyses were performed using biomarkers for activated microglia/macrophages, astrocytes, blood-brain barrier leakage, and neuronal nuclei to determine the degree of foreign body response (FBR) resulting from the implanted microelectrodes. Despite its well-known acute anti-biofouling property, we observed that PEG-coated devices caused no significantly different FBR compared to non-coated controls at 4 weeks. A repetition using CX3CR1-GFP mice cohort showed similar results. Our histological findings suggest that there is no significant impact of acute delivery of PEG on the FBR in the long-term, and that temporary increase in the device footprint due to the coating of PEG also does not have a significant impact. Large variability seen within the same treatment group also implies that avoiding large superficial vasculature during implantation is not sufficient to minimize inter-animal variability. PMID:28959183

76 FR 50111 - Airworthiness Directives; Fokker Services B.V. Model F.28 Mark 1000, 2000, 3000, and 4000 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-12

... Directives; Fokker Services B.V. Model F.28 Mark 1000, 2000, 3000, and 4000 Airplanes AGENCY: Federal... Services B.V. Model F.28 Mark 1000, 2000, 3000, and 4000 airplanes, certificated in any category, all...

Targeted PEG-based bioconjugates enhance the cellular uptake and transport of a HIV-1 TAT nonapeptide.

PubMed

Ramanathan, S; Qiu, B; Pooyan, S; Zhang, G; Stein, S; Leibowitz, M J; Sinko, P J

2001-12-13

We previously described the enhanced cell uptake and transport of R.I-K(biotin)-Tat9, a large ( approximately 1500 Da) peptidic inhibitor of HIV-1 Tat protein, via SMVT, the intestinal biotin transporter. The aim of the present study was to investigate the feasibility of targeting biotinylated PEG-based conjugates to SMVT in order to enhance cell uptake and transport of Tat9. The 29 kDa peptide-loaded bioconjugate (PEG:(R.I-Cys-K(biotin)-Tat9)8) used in these studies contained eight copies of R.I-K(biotin)-Tat9 appended to PEG by means of a cysteine linkage. The absorptive transport of biotin-PEG-3400 (0.6-100 microM) and the bioconjugate (0.1-30 microM) was studied using Caco-2 cell monolayers. Inhibition of biotin-PEG-3400 by positive controls (biotin, biocytin, and desthiobiotin) was also determined. Uptake of these two compounds was also determined in CHO cells transfected with human SMVT (CHO/hSMVT) and control cells (CHO/pSPORT) over the concentration ranges of 0.05-12.5 microM and 0.003-30 microM, respectively. Nonbiotinylated forms of these two compounds, PEG-3350 and PEG:(R.I-Cys-K-Tat9)8, were used in the control studies. Biotin-PEG-3400 transport was found to be concentration-dependent and saturable in Caco-2 cells (K(m)=6.61 microM) and CHO/hSMVT cells (K(m)=1.26 microM). Transport/uptake was significantly inhibited by positive control substrates of SMVT. PEG:(R.I-Cys-K(biotin)Tat9)8 also showed saturable transport kinetics in Caco-2 cells (K(m)=6.13 microM) and CHO/hSMVT cells (K(m)=8.19 microM). Maximal uptake in molar equivalents of R.I-Cys-K(biotin)Tat9 was 5.7 times greater using the conjugate versus the biotinylated peptide alone. Transport of the nonbiotinylated forms was significantly lower (P<0.001) in all cases. The present results demonstrate that biotin-PEG-3400 and PEG:(R.I-Cys-K(biotin)Tat9)8 interact with human SMVT to enhance the cellular uptake and transport of these larger molecules and that targeted bioconjugates may have potential

Exosome purification based on PEG-coated Fe3O4 nanoparticles.

PubMed

Chang, Ming; Chang, Yaw-Jen; Chao, Pei Yu; Yu, Qing

2018-01-01

Cancer cells secrete many exosomes, which facilitate metastasis and the later growth of cancer. For early cancer diagnosis, the detection of exosomes is a crucial step. Exosomes exist in biological fluid, such as blood, which contains various proteins. It is necessary to remove the proteins in the biological fluid to avoid test interference. This paper presented a novel method for exosome isolation using Fe3O4 magnetic nanoparticles (MNPs), which were synthesized using the chemical co-precipitation method and then coated with polyethylene glycol (PEG). The experimental results showed that the diameter of the PEG-coated Fe3O4 nanoparticles was about 20 nm, while an agglomerate of MNPs reached hundreds of nanometers in size. In the protein removal experiments, fetal bovine serum (FBS) was adopted as the analyte for bioassays of exosome purification. PEG-coated Fe3O4 MNPs reduced the protein concentration in FBS to 39.89% of the original solution. By observing a particle size distribution of 30~200 nm (the size range of various exosomes), the exosome concentrations were kept the same before and after purification. In the gel electrophoresis experiments, the bands of CD63 (~53 kDa) and CD9 (~22 kDa) revealed that exosomes existed in FBS as well as in the purified solution. However, the bands of the serum albumins (~66 kDa) and the various immunoglobulins (around 160 ~ 188 kDa) in the purified solution's lane explained that most proteins in FBS were removed by PEG-coated Fe3O4 MNPs. When purifying exosomes from serum, protein removal is critical for further exosome investigation. The proposed technique provides a simple and effective method to remove proteins in the serum using the PEG-coated Fe3O4 MNPs.

Therapeutic PEG-ceramide nanomicelles synergize with salinomycin to target both liver cancer cells and cancer stem cells.

PubMed

Wang, Meiping; Xie, Fangyuan; Wen, Xikai; Chen, Han; Zhang, Hai; Liu, Junjie; Zhang, He; Zou, Hao; Yu, Yuan; Chen, Yan; Sun, Zhiguo; Wang, Xinxia; Zhang, Guoqing; Yin, Chuan; Sun, Duxin; Gao, Jie; Jiang, Beige; Zhong, Yanqiang; Lu, Ying

2017-05-01

Salinomycin (SAL)-loaded PEG-ceramide nanomicelles (SCM) were prepared to target both liver cancer cells and cancer stem cells. The synergistic ratio of SAL/PEG-ceramide was evaluated to prepare SCM, and the antitumor activity of SCM was examined both in vitro and in vivo. SAL/PEG-ceramide molar ratio of 1:4 was chosen as the synergistic ratio, and SCM showed superior cytotoxic effect and increased apoptosis-inducing activity in both liver cancer cells and cancer stem cells. In vivo, SCM showed the best tumor inhibitory effect with a safety profile. Thus, PEG-ceramide nanomicelles could serve as an effective and safe therapeutic drug carrier to deliver SAL into liver cancer, opening up the avenue of using PEG-ceramide as therapeutic drug carriers.

Strong variable linear polarization in the cool active star II Peg

NASA Astrophysics Data System (ADS)

Rosén, Lisa; Kochukhov, Oleg; Wade, Gregg A.

2014-08-01

Magnetic fields of cool active stars are currently studied polarimetrically using only circular polarization observations. This provides limited information about the magnetic field geometry since circular polarization is only sensitive to the line-of-sight component of the magnetic field. Reconstructions of the magnetic field topology will therefore not be completely trustworthy when only circular polarization is used. On the other hand, linear polarization is sensitive to the transverse component of the magnetic field. By including linear polarization in the reconstruction the quality of the reconstructed magnetic map is dramatically improved. For that reason, we wanted to identify cool stars for which linear polarization could be detected at a level sufficient for magnetic imaging. Four active RS CVn binaries, II Peg, HR 1099, IM Peg, and σ Gem were observed with the ESPaDOnS spectropolarimeter at the Canada-France-Hawaii Telescope. Mean polarization profiles in all four Stokes parameters were derived using the multi-line technique of least-squares deconvolution (LSD). Not only was linear polarization successfully detected in all four stars in at least one observation, but also, II Peg showed an extraordinarily strong linear polarization signature throughout all observations. This qualifies II Peg as the first promising target for magnetic Doppler imaging in all four Stokes parameters and, at the same time, suggests that other such targets can possibly be identified.

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

PubMed Central

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

2016-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2016-08-01

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

Preventing False Negatives for Histochemical Detection of Phenolics and Lignins in PEG-Embedded Plant Tissues

PubMed Central

Ferreira, Bruno G.; Falcioni, Renan; Guedes, Lubia M.; Avritzer, Sofia C.; Antunes, Werner C.; Souza, Luiz A.; Isaias, Rosy M.S.

2016-01-01

Polyethylene glycol (PEG) is a low-cost and advantageous embedding medium, which maintains the majority of cell contents unaltered during the embedding process. Some hard or complex plant materials are better embedded in PEG than in other usual embedding media. However, the histochemical tests for phenolics and lignins in PEG-embedded plant tissues commonly result in false negatives. We hypothesize that these false negatives should be prevented by the use of distinct fixatives, which should avoid the bonds between PEG and phenols. Novel protocols for phenolics and flavanols detection are efficiently tested, with fixation of the samples in ferrous sulfate and formalin or in caffeine and sodium benzoate, respectively. The differentiation of lignin types is possible in safranin-stained sections observed under fluorescence. The Maule’s test faultlessly distinguishes syringyl-rich from guaiacyl- and hydroxyphenyl-rich lignins in PEG-embedded material under light microscopy. Current hypothesis is corroborated, that is, the adequate fixation solves the false-negative results, and the new proposed protocols fill up some gaps on the detection of phenolics and lignins. PMID:28117630

Update on PEG-interferon α-2b as adjuvant therapy in melanoma.

PubMed

Di Trolio, Rossella; Simeone, Ester; Di Lorenzo, Giuseppe; Grimaldi, Antonio Maria; Romano, Anna; Ayala, Fabrizio; Caracò, Corrado; Mozzillo, Nicola; Ascierto, Paolo A

2012-09-01

Based on the results of European Organization for Research and Treatment of Cancer (EORTC) 18991 trial, the US Food and Drug Administration (FDA) approved PEG-interferon α-2b (PEG-IFN) (Sylatron) as adjuvant therapy for high-risk melanoma. The EORTC 18991 trial was an open-label study of resectable stage III melanoma with 1,256 patients who were randomized to observation-alone or to treatment with PEG-IFN for up to 5 years. The median recurrence-free survival of the treatment groups was significantly longer, while overall survival, a secondary endpoint, was not significantly different between the two groups. This review, after a short summary of interferon α-2b trials, critically analyzes the EORTC18991 trial, as well as the subgroup results and future perspectives for this stage of disease.

Optimization of PEG-based extraction of polysaccharides from Dendrobium nobile Lindl. and bioactivity study.

PubMed

Zhang, Yi; Wang, Hongxin; Wang, Peng; Ma, ChaoYang; He, GuoHua; Rahman, Md Ramim Tanver

2016-11-01

Polyethylene glycol (PEG) as a green solvent was employed to extract polysaccharide. The optimal conditions for PEG-based ultrasonic extraction of Dendrobium nobile Lindl. polysaccharide (JCP) were determined by response surface methodology. Under the optimal conditions: extraction temperature of 58.5°C; ultrasound power of 193W, and the concentration of polyethylene glycol-200 (PEG-200) solution of 45%, the highest JCP yield was obtained as 15.23±0.57%, which was close to the predicted yield, 15.57%. UV and FT-IR analysis revealed the general characteristic absorption peaks of both JCP with water extraction (JCP w ) and PEG-200 solvent extraction (JCP p ). Thermal analysis of both JCPs was performed with Thermal Gravimetric Analyzer (TGA) and Differential Scanning Calorimeter (DSC). Antioxidant activities of two polysaccharides were also compared and no significant difference in vitro was obtained. Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical peeling by SA-PEG remodels photo-damaged skin: suppressing p53 expression and normalizing keratinocyte differentiation.

PubMed

Dainichi, Teruki; Amano, Satoshi; Matsunaga, Yukiko; Iriyama, Shunsuke; Hirao, Tetsuji; Hariya, Takeshi; Hibino, Toshihiko; Katagiri, Chika; Takahashi, Motoji; Ueda, Setsuko; Furue, Masutaka

2006-02-01

Chemical peeling with salicylic acid in polyethylene glycol vehicle (SA-PEG), which specifically acts on the stratum corneum, suppresses the development of skin tumors in UVB-irradiated hairless mice. To elucidate the mechanism through which chemical peeling with SA-PEG suppresses skin tumor development, the effects of chemical peeling on photodamaged keratinocytes and cornified envelopes (CEs) were evaluated in vivo. Among UVB-irradiated hairless mice, the structural atypia and expression of p53 protein in keratinocytes induced by UVB irradiation were intensely suppressed in the SA-PEG-treated mice 28 days after the start of weekly SA-PEG treatments when compared to that in the control UVB-irradiated mice. Incomplete expression of filaggrin and loricrin in keratinocytes from the control mice was also improved in keratinocytes from the SA-PEG-treated mice. In photo-exposed human facial skin, immature CEs were replaced with mature CEs 4 weeks after treatment with SA-PEG. Restoration of photodamaged stratum corneum by treatment with SA-PEG, which may affect remodeling of the structural environment of the keratinocytes, involved the normalization of keratinocyte differentiation and suppression of skin tumor development. These results suggest that the stratum corneum plays a protective role against carcinogenesis, and provide a novel strategy for the prevention of photo-induced skin tumors.

A Prospective Randomized Controlled Trial of AJG522 versus Standard PEG + E as Bowel Preparation for Colonoscopy

PubMed Central

Sagawa, Toshihiko; Tomizawa, Taku; Mizuide, Masafumi; Yasuoka, Hidetoshi; Shimoyama, Yasuyuki; Kakizaki, Satoru; Kawamura, Osamu; Kusano, Motoyasu; Yamada, Masanobu

2015-01-01

Polyethylene glycol- (PEG-) based bowel preparations for colonoscopies are often poorly tolerated due to the large volumes of fluid intake required. We compared low-volume “modified” PEG + ascorbic acid (AJG522) with standard PEG with electrolytes (PEG + E) in addition to a stimulant laxative and an agent to improve bowel function for the bowel cleansing before colonoscopy to evaluate its efficacy, safety, and acceptability. Outpatients scheduled to undergo colonoscopy were randomized to receive either AJG522 or PEG + E. Bowel cleansing conditions were assessed via macroscopic fecal findings by blinded and independent investigators. A survey of the patients' feedback regarding the preparation was conducted by questionnaire. Successful cleansing was achieved in all cases, except for 4 cases in the PEG + E group, at 3 hours after taking the preparation. The fecal properties were significantly clearer in the AJG522 group than in the PEG + E group at 2 hours after taking each preparation (P = 0.013). Although the total liquid volume of the bowel preparation was not reduced, the AJG522 preparation could significantly reduce the required volume of the preparation (P < 0.0001). Moreover, the patients in the AJG522 group had better acceptability (P = 0.010). There were no significant differences in the safety profiles between groups (UMIN000013892). PMID:25688357

Oral PEG 15-20 protects the intestine against radiation : role of lipid rafts.

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

Valuckaite, V.; Zaborina, O.; Long, J.

Intestinal injury following abdominal radiation therapy or accidental exposure remains a significant clinical problem that can result in varying degrees of mucosal destruction such as ulceration, vascular sclerosis, intestinal wall fibrosis, loss of barrier function, and even lethal gut-derived sepsis. We determined the ability of a high-molecular-weight polyethylene glycol-based copolymer, PEG 15-20, to protect the intestine against the early and late effects of radiation in mice and rats and to determine its mechanism of action by examining cultured rat intestinal epithelia. Rats were exposed to fractionated radiation in an established model of intestinal injury, whereby an intestinal segment is surgicallymore » placed into the scrotum and radiated daily. Radiation injury score was decreased in a dose-dependent manner in rats gavaged with 0.5 or 2.0 g/kg per day of PEG 15-20 (n = 9-13/group, P < 0.005). Complementary studies were performed in a novel mouse model of abdominal radiation followed by intestinal inoculation with Pseudomonas aeruginosa (P. aeruginosa), a common pathogen that causes lethal gut-derived sepsis following radiation. Mice mortality was decreased by 40% in mice drinking 1% PEG 15-20 (n = 10/group, P < 0.001). Parallel studies were performed in cultured rat intestinal epithelial cells treated with PEG 15-20 before radiation. Results demonstrated that PEG 15-20 prevented radiation-induced intestinal injury in rats, prevented apoptosis and lethal sepsis attributable to P. aeruginosa in mice, and protected cultured intestinal epithelial cells from apoptosis and microbial adherence and possible invasion. PEG 15-20 appeared to exert its protective effect via its binding to lipid rafts by preventing their coalescence, a hallmark feature in intestinal epithelial cells exposed to radiation.« less

Redox-sensitive micelles assembled from amphiphilic mPEG-PCL-SS-DTX conjugates for the delivery of docetaxel.

PubMed

Zhang, Huiyuan; Wang, Kaiming; Zhang, Pei; He, Wenxiu; Song, Aixin; Luan, Yuxia

2016-06-01

Docetaxel (DTX) can produce anti-tumor effects by inhibiting cell growth and inducing apoptosis. However, the poor solubility of DTX restricts its application and its clinical formulation has caused serious adverse reaction due to the use of Tween-80. In the present study, DTX was conjugated to an amphiphilic di-block polymer to solve these problems. Methoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) was selected as the polymer skeleton and a redox sensitive disulfide bond was used as the linker between DTX and mPEG-PCL. The synthesized mPEG-PCL-SS-DTX conjugates were characterized by (1)H-nuclear magnetic resonance ((1)H NMR) and Fourier transform infrared spectroscopy (FTIR). Interestingly, the mPEG-PCL-SS-DTX conjugates could self-assemble into micelles in aqueous solution. The critical micelle concentration (CMC) of mPEG-PCL-SS-DTX micelles was about 2.3mgL(-1) determined using pyrene molecule fluorescent probe method while the size of mPEG-PCL-SS-DTX micelles was determined to be ca. 17.6nm and 116.0nm with a bimodal distribution by dynamic light scattering (DLS). The in vitro release results indicated that the as-prepared micelles exhibited a sustained release profile with good redox sensitive properties. In particular, the hemolytic toxicity test indicated the as-prepared mPEG-PCL-SS-DTX micelles had negligible hemolytic activity, demonstrating their safety in drug delivery system. Cytotoxicity assay of the mPEG-PCL-SS-DTX micelles verified their highly enhanced cytotoxicity to MCF-7/A and A549 cells. These results thus demonstrated that the present redox-sensitive mPEG-PCL-SS-DTX micelle was an efficient and safe sustained drug delivery system in the biomedical area. Copyright © 2016 Elsevier B.V. All rights reserved.

Biodegradable self-assembled PEG-PCL-PEG micelles for hydrophobic honokiol delivery: I. Preparation and characterization

NASA Astrophysics Data System (ADS)

Gong, ChangYang; Wei, XiaWei; Wang, XiuHong; Wang, YuJun; Guo, Gang; Mao, YongQiu; Luo, Feng; Qian, ZhiYong

2010-05-01

This study aims to develop self-assembled poly(ethylene glycol)-poly(ɛ-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) micelles to encapsulate hydrophobic honokiol (HK) in order to overcome its poor water solubility and to meet the requirement of intravenous administration. Honokiol loaded micelles (HK-micelles) were prepared by self-assembly of PECE copolymer in aqueous solution, triggered by its amphiphilic characteristic assisted by ultrasonication without any organic solvents, surfactants and vigorous stirring. The particle size of the prepared HK-micelles measured by Malvern laser particle size analyzer were 58 nm, which is small enough to be a candidate for an intravenous drug delivery system. Furthermore, the HK-micelles could be lyophilized into powder without any adjuvant, and the re-dissolved HK-micelles are stable and homogeneous with particle size about 61 nm. Furthermore, the in vitro release profile showed a significant difference between the rapid release of free HK and the much slower and sustained release of HK-micelles. Moreover, the cytotoxicity results of blank micelles and HK-micelles showed that the PECE micelle was a safe carrier and the encapsulated HK retained its potent antitumor effect. In short, the HK-micelles were successfully prepared by an improved method and might be promising carriers for intravenous delivery of HK in cancer chemotherapy, being effective, stable, safe (organic solvent and surfactant free), and easy to produce and scale up.

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.

Randomized clinical trial: macrogol/PEG 3350 plus electrolytes for treatment of patients with constipation associated with irritable bowel syndrome.

PubMed

Chapman, R W; Stanghellini, V; Geraint, M; Halphen, M

2013-09-01

Polyethylene glycol (PEG) 3350 plus electrolytes (PEG 3350+E) is an established treatment for constipation and has been proposed as a treatment option for constipation associated with irritable bowel syndrome (IBS-C). This study aimed to compare the efficacy and safety of PEG 3350+E vs. placebo in adult patients with IBS-C. Following a 14-day run-in period without study medication, patients with confirmed IBS-C were randomized to receive PEG 3350+E (N=68) or placebo (N=71) for 28 days. The primary endpoint was the mean number of spontaneous bowel movements (SBMs) per day in the last treatment week. In both groups, mean weekly number of SBMs (±s.d.) increased from run-in. The difference between the groups in week 4 (PEG 3350+E, 4.40±2.581; placebo, 3.11±1.937) was statistically significant (95% confidence interval: 1.17, 1.95; P<0.0001). Although mean severity score for abdominal discomfort/pain was significantly reduced compared with run-in with PEG 3350+E, there was no difference vs. placebo. Spontaneous complete bowel movements, responder rates, stool consistency, and severity of straining also showed superior improvement in the PEG 3350+E group over placebo in week 4. The most common drug related treatment-emergent adverse events were abdominal pain (PEG 3350+E, 4.5%; placebo, 0%) and diarrhoea (PEG 3350+E, 4.5%; placebo, 4.3%). In IBS-C, PEG 3350+E was superior to placebo for relief of constipation, and although a statistically significant improvement in abdominal discomfort/pain was observed compared with baseline, there was no associated improvement compared with placebo. PEG 3350+E is a well-established and effective treatment that should be considered suitable for use in IBS-C.

Bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles as novel tumor targeting carriers

NASA Astrophysics Data System (ADS)

Ding, Hong; Yong, Ken-Tye; Roy, Indrajit; Hu, Rui; Wu, Fang; Zhao, Lingling; Law, Wing-Cheung; Zhao, Weiwei; Ji, Wei; Liu, Liwei; Bergey, Earl J.; Prasad, Paras N.

2011-04-01

In this study, we have developed a novel carrier, micelle-type bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles (NPs), for the detection and treatment of pancreatic cancer. These NPs contained 4-arm-PEG as corona, and PLGA as core, the particle surface was conjugated with cyclo(arginine-glycine-aspartate) (cRGD) as ligand for in vivo tumor targeting. The hydrodynamic size of the NPs was determined to be 150-180 nm and the critical micellar concentration (CMC) was estimated to be 10.5 mg l - 1. Our in vitro study shows that these NPs by themselves had negligible cytotoxicity to human pancreatic cancer (Panc-1) and human glioblastoma (U87) cell lines. Near infrared (NIR) microscopy and flow cytometry demonstrated that the cRGD conjugated PLGA-4-arm-PEG polymeric NPs were taken up more efficiently by U87MG glioma cells, over-expressing the αvβ3 integrin, when compared with the non-targeted NPs. Whole body imaging showed that the cRGD conjugated PLGA-4-arm-PEG branched polymeric NPs had the highest accumulation in the pancreatic tumor site of mice at 48 h post-injection. Physical, hematological, and pathological assays indicated low in vivo toxicity of this NP formulation. These studies on the ability of these bioconjugated PLGA-4-arm-PEG polymeric NPs suggest that the prepared polymeric NPs may serve as a promising platform for detection and targeted drug delivery for pancreatic cancer.

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

NASA Astrophysics Data System (ADS)

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

2018-01-01

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

Construction and characterization of Gal-chitosan graft methoxy poly (ethylene glycol) (Gal-CS-mPEG) nanoparticles as efficient gene carrier

NASA Astrophysics Data System (ADS)

Jin, Jiting; Fu, Wandong; Liao, Miaofei; Han, Baoqin; Chang, Jing; Yang, Yan

2017-10-01

In the present study, galactosylated chitosan (Gal-CS) was conjugated with methoxy poly(ethylene glycol) (mPEG) as a hydrophilic group. The structure of Gal-CS-mPEG polymer was characterized and the nanoparticles (NPs) were prepared using ironic gelation method. The study was designed to investigate the characteristics and functions of Gal-CS-mPEG NPs. The morphology of Gal-CS-mPEG NPs was observed by SEM and it was a compact and spherical shape. The size of the NPs was approximately 200 nm in diameter under the ideal process parameters. The interaction between Gal-CS-mPEG NPs and pDNA, and the protection of pDNA against DNase I and serum degradation by Gal-CS-mPEG NPs were evaluated. Agarose gel electrophoresis results showed that Gal-CS-mPEG NPs had strong interaction with pDNA at the weight ratio of 12:1, 4:1 and 2:1 and could protect pDNA from DNase I and serum degradation. Gal-CS-mPEG NPs exhibited high loading efficiency and sustainable in vitro release. The blood compatibility studies demonstrated that Gal-CS-mPEG NPs had superior compatibility with erythrocytes in terms of aggregation degree and hemolysis level. Gal-CS-mPEG NPs showed no cytotoxicity on L929 cells, which is a normal mouse connective tissue fibroblast, but showed inhibitory effects on the proliferation of Bel-7402 cells, which is a liver cancer cell line. In conclusion, Gal-CS-mPEG NP is a bio-safe and efficient gene carrier with potential application in gene delivery.

Evaluation of BSA protein release from hollow hydroxyapatite microspheres into PEG hydrogel

PubMed Central

Fu, Hailuo; Rahaman, Mohamed N.; Brown, Roger F.; Day, Delbert E.

2013-01-01

Implants that simultaneously function as an osteoconductive matrix and as a device for local drug or growth factor delivery could provide an attractive system for bone regeneration. In our previous work, we prepared hollow hydroxyapatite (abbreviated HA) microspheres with a high surface area, mesoporous shell wall and studied the release of a model protein, bovine serum albumin (BSA), from the microspheres into phosphate-buffered saline (PBS). The present work is an extension of our previous work to study the release of BSA from similar HA microspheres into a biocompatible hydrogel, poly(ethylene glycol) (PEG). BSA-loaded HA microspheres were placed in a PEG solution which was rapidly gelled using ultraviolet radiation. The BSA release rate into the PEG hydrogel, measured using a spectrophotometric method, was slower than into PBS, and it was dependent on the initial BSA loading and on the microstructure of the microsphere shell wall. A total of 35–40% of the BSA initially loaded into the microspheres was released into PEG over ~14 days. The results indicate that these hollow HA microspheres have promising potential as an osteoconductive device for local drug or growth factor delivery in bone regeneration and in the treatment of bone diseases. PMID:23498254

[PEG-chitosan branched copolymers to improve the biocatalytic properties of Erwinia carotovora recombinant L-asparaginase].

PubMed

Kudryashova, E V; Suhoverkov, K V; Sokolov, N N

2015-01-01

A new approach to the regulation of catalytic properties of medically relevant enzymes has been proposed using the novel recombinant preparation of L-asparaginase from Erwinia carotovora (EwA), a promising antitumor agent. New branched co-polymers of different composition based on chitosan modified with polyethylene glycol (PEG) molecules, designated as PEG-chitosan, have been synthesized. PEG-chitosan copolymers were further conjugated with EwA. In order to optimize the catalytic properties of asparaginase two types of conjugates differing in their architecture have been synthesized: (1) crown-type conjugates were synthesized by reductive amination reaction between the reducing end of the PEG-chitosan copolymer and enzyme amino groups; (2) multipoint-conjugates were synthesized using the reaction of multipoint amide bond formation between PEG-chitosan amino groups and carboxyl groups of the enzyme in the presence of the Woodward's reagent. The structure and composition of these conjugates were determined by IR spectroscopy. The content of the copolymers in the conjugates was controlled by the characteristic absorption band of C-O-C bonds in the PEG structure at the frequency of 1089 cm-1. The study of catalytic characteristics of EwA preparations by conductometry showed that at physiological pH values the enzyme conjugates with PEG-chitosan with optimized structure and the optimal composition demonstrated 5-8-fold higher catalytic efficiency (kcat/Km) than the native enzyme. To certain extent, this can be attributed to favorable shift of pH-optima in result of positively charged amino-groups introduction in the vicinity of the active site. The proposed approach, chito-pegylation, is effective for regulating the catalytic and pharmacokinetic properties of asparaginase, and is promising for the development of prolonged action dosage forms for other enzyme therapeutics.

Quantitative analysis of polyethylene glycol (PEG) and PEGylated proteins in animal tissues by LC-MS/MS coupled with in-source CID.

PubMed

Gong, Jiachang; Gu, Xiaomei; Achanzar, William E; Chadwick, Kristina D; Gan, Jinping; Brock, Barry J; Kishnani, Narendra S; Humphreys, W Griff; Iyer, Ramaswamy A

2014-08-05

The covalent conjugation of polyethylene glycol (PEG, typical MW > 10k) to therapeutic peptides and proteins is a well-established approach to improve their pharmacokinetic properties and diminish the potential for immunogenicity. Even though PEG is generally considered biologically inert and safe in animals and humans, the slow clearance of large PEGs raises concerns about potential adverse effects resulting from PEG accumulation in tissues following chronic administration, particularly in the central nervous system. The key information relevant to the issue is the disposition and fate of the PEG moiety after repeated dosing with PEGylated proteins. Here, we report a novel quantitative method utilizing LC-MS/MS coupled with in-source CID that is highly selective and sensitive to PEG-related materials. Both (40K)PEG and a tool PEGylated protein (ATI-1072) underwent dissociation in the ionization source of mass spectrometer to generate a series of PEG-specific ions, which were subjected to further dissociation through conventional CID. To demonstrate the potential application of the method to assess PEG biodistribution following PEGylated protein administration, a single dose study of ATI-1072 was conducted in rats. Plasma and various tissues were collected, and the concentrations of both (40K)PEG and ATI-1072 were determined using the LC-MS/MS method. The presence of (40k)PEG in plasma and tissue homogenates suggests the degradation of PEGylated proteins after dose administration to rats, given that free PEG was absent in the dosing solution. The method enables further studies for a thorough characterization of disposition and fate of PEGylated proteins.

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

PubMed

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

2001-11-01

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

The curious ability of PEG-fusion technologies to restore lost behaviors after nerve severance

PubMed Central

Bittner, G.D.; Sengelaub, D.R.; Trevino, R.C.; Peduzzi, J.D.; Mikesh, M.; Ghergherehchi, C.L.; Schallert, T.; Thayer, W.P.

2016-01-01

Traumatic injuries to PNS and CNS axons are not uncommon. Restoration of lost behaviors following severance of mammalian peripheral nerve axons (PNAs) relies on regeneration by slow outgrowths and is typically poor or nonexistent if after ablation or injuries close to the soma. Behavioral recovery after severing spinal tract axons (STAs) is poor because STAs do not naturally regenerate. Current techniques to enhance PNA and/or STA regeneration have had limited success and do not prevent the onset of Wallerian degeneration of severed distal segments. This review describes the use of a recently-developed polyethylene glycol (PEG)-fusion technology combining concepts in biochemical engineering, cell biology and clinical microsurgery. Within minutes after micro-suturing carefully-trimmed cut ends and applying a well-specified sequence of solutions, PEG-fused axons exhibit morphological continuity (assessed by intra-axonal dye diffusion) and electrophysiological continuity (assessed by conduction of action potentials) across the lesion site. Wallerian degeneration of PEG-fused PNAs is greatly reduced as measured by counts of sensory and/or motor axons, and maintenance of axonal diameters and neuromuscular synapses. After PEG-fusion repair, cut- or crush-severed or ablated PNAs or crush-severed STAs rapidly (within days to weeks), more completely, and permanently restore PNA- or STA-mediated behaviors compared to non-treated or conventionally-treated animals. PEG-fusion success is enhanced or decreased by applying anti-oxidants or oxidants, trimming cut ends or stretching axons, exposure to Ca2+-free or - containing solutions, respectively. PEG-fusion technology employs surgical techniques and chemicals already used by clinicians and has the potential to produce a paradigm-shift in the treatment of traumatic injuries to PNAs and STAs. PMID:26525605

Polyethylene glycol (PEG) assisted size-controlled SnO{sub 2} nanoparticles by sol-gel process

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

Tripathi, P., E-mail: ptrip71@yahoo.com; Ahmed, Ateeq; Ali, Tinku

2016-05-23

Tetragonal phase tin oxide (SnO{sub 2}) nanoparticles have been synthesized by sol–gel method using SnCl{sub 4}.5H{sub 2}O and polyethylene glycol (PEG) of different concentration. The phase, size and purity of the final products are characterized by X-ray diffraction (XRD). The morphology is confirmed by scanning electron microscopy (SEM) analysis. There exists relationship between the concentration of PEG and particle size of SnO{sub 2} nanoparticles. Increase in concentration of PEG caused the reduction of particle size of tin oxide nanoparticles. The results suggest that the concentration of PEG plays a significant role in determining the size of SnO{sub 2} nanoparticles synthesizedmore » via this method. The optical property of the product has been explored by Ultraviolet (UV-visible) and Fourier Transform Infrared (FTIR) spectroscopic techniques.« less

Energy metabolism analysis reveals the mechanism of inhibition of breast cancer cell metastasis by PEG-modified graphene oxide nanosheets.

PubMed

Zhou, Teng; Zhang, Bo; Wei, Peng; Du, Yipeng; Zhou, Hejiang; Yu, Meifang; Yan, Liang; Zhang, Wendi; Nie, Guangjun; Chen, Chunying; Tu, Yaping; Wei, Taotao

2014-12-01

Recent advances in nanomedicine provide promising alternatives for cancer treatment that may improve the survival of patients with metastatic disease. The goal of the present study was to evaluate graphene oxide (GO) as a potential anti-metastatic agent. For this purpose, GO was modified with polyethylene glycol (PEG) to form PEG-modified GO (PEG-GO), which improves its aqueous stability and biocompatibility. We show here that PEG-GO exhibited no apparent effects on the viability of breast cancer cells (MDA-MB-231, MDA-MB-436, and SK-BR-3) or non-cancerous cells (MCF-10A), but inhibited cancer cell migration in vitro and in vivo. Analysis of cellular energy metabolism revealed that PEG-GO significantly impaired mitochondrial oxidative phosphorylation (OXPHOS) in breast cancer cells; however, PEG-GO showed no effect on OXPHOS in non-cancerous cells. To explore the underlying mechanisms, a SILAC (Stable Isotope Labeling by Amino acids in Cell culture) labeling strategy was used to quantify protein expression in PEG-GO-exposed breast cancer versus non-cancerous cells. The results indicated that PEG-GO selectively down-regulated PGC-1α in breast cancer cells and thus modified the expression of diverse energy generation-related proteins, which accounts for the inhibition of OXPHOS. The inhibition of OXPHOS by PEG-GO significantly reduced ATP production and impaired assembly of the F-actin cytoskeleton in breast cancer cells, which is required for the migratory and invasive phenotype of cancer cells. Taken together, these effects of PEG-GO on cancer cell metastasis may allow the development of a new approach to treat metastatic breast cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ionic depletion at the crystalline Gibbs layer of PEG-capped gold nanoparticle brushes at aqueous surfaces

NASA Astrophysics Data System (ADS)

Wang, Wenjie; Zhang, Honghu; Mallapragada, Surya; Travesset, Alex; Vaknin, David

2017-12-01

In situ surface-sensitive x-ray diffraction and grazing incidence x-ray fluorescence spectroscopy (GIXFS) methods are combined to determine the ionic distributions across the liquid/vapor interfaces of thiolated-polyethylene-glycol-capped gold nanoparticle (PEG-AuNP) solutions. Induced by the addition of salts (i.e., Cs2SO4 ) to PEG-AuNPs solutions, two-dimensional hexagonal lattices of PEG-AuNPs form spontaneously at the aqueous surfaces, as is demonstrated by x-ray reflectivity and grazing incidence small-angle x-ray scattering. By taking advantage of element specificity with the GIXFS method, we find that the cation Cs+ concentration at the crystalline film is significantly reduced in parts of the PEG-AuNP film compared with that in the bulk.

Evaluation of self-assembled HCPT-loaded PEG-b-PLA nanoparticles by comparing with HCPT-loaded PLA nanoparticles.

PubMed

Yang, Xiangrui; Wu, Shichao; Wang, Yange; Li, Yang; Chang, Di; Luo, Yin; Ye, Shefang; Hou, Zhenqing

2014-12-01

We present a dialysis technique to prepare the 10-hydroxycamptothecin (HCPT)-loaded nanoparticles (NPs) using methoxypolyethylene glycol-poly(D,L-lactide) (PEG-b-PLA) and PLA, respectively. Both HCPT-loaded PEG-b-PLA NPs and HCPT-loaded PLA NPs were characterized by differential scanning calorimetry (DSC), dynamic light scattering (DLS), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The results showed that the HCPT-loaded PEG-b-PLA NPs and HCPT-loaded PLA NPs presented a hydrodynamic particle size of 120.1 and 226.8 nm, with a polydispersity index of 0.057 and 0.207, a zeta potential of -31.2 and -45.7 mV, drug encapsulation efficiency of 44.52% and 44.94%, and drug-loaded content of 7.42% and 7.49%, respectively. The HCPT-loaded PEG-b-PLA NPs presented faster drug release rate compared to the HCPT-loaded PLA NPs. The HCPT-loaded PEG-b-PLA NPs presented higher cytotoxicity than the HCPT-loaded PLA NPs. These results suggested that the HCPT-loaded PEG-b-PLA NPs presented better characteristics for drug delivery compared to HCPT-loaded PLA NPs.

Optimization Properties of Environmentally Friendly Paper Coating Based Starch-Polyethylene glycol (PEG) Mixture

NASA Astrophysics Data System (ADS)

Galih Saputri, Diani; Khairuddin; Dwi Nurhayati, Nanik; Pham, Trinh

2017-11-01

The use of starch as biodegradable base material for packaging application was of great interest as an environmentally friendly alternative to the present use of polyethylene and polyvinyl chloride. However, starch tended to be brittle and had a lack of stability due to exposure to water. Several aproaches have been done to improve shellac properties including through chemical modification, mixing with polymers, clays, and plasticizers. The present study related to optimization of starch properties when mixing with polyethylene glycol (PEG) coated on the paper. The aim was to obtain the temperature and mixing time between starch and PEG so produced composites with optimal barrier properties. The composites of PEG/starch 10 % w/w were prepared using solvent casting and coated on paper surface, and dried in the oven for 12 hours at 40°C. Water Vapour Transmitter Rate (WVTR) (Payne cup method) showed that 70°C was the optimum temperature when mixing time was 30 minutes. Moreover, it showed that the optimum mixing time was 30 minutes when mixing temperature was 80 and 70 °C. Fourier Transform Infra Red (FTIR) showed a strong interaction between PEG400 and starch.

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

PubMed Central

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

1998-01-01

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

Zwitterionic PEG-PC Hydrogels Modulate the Foreign Body Response in a Modulus-Dependent Manner.

PubMed

Jansen, Lauren E; Amer, Luke D; Chen, Esther Y-T; Nguyen, Thuy V; Saleh, Leila S; Emrick, Todd; Liu, Wendy F; Bryant, Stephanie J; Peyton, Shelly R

2018-05-15

Reducing the foreign body response (FBR) to implanted biomaterials will enhance their performance in tissue engineering. Poly(ethylene glycol) (PEG) hydrogels are increasingly popular for this application due to their low cost, ease of use, and the ability to tune their compliance via molecular weight and cross-linking densities. PEG hydrogels can elicit chronic inflammation in vivo, but recent evidence has suggested that extremely hydrophilic, zwitterionic materials and particles can evade the immune system. To combine the advantages of PEG-based hydrogels with the hydrophilicity of zwitterions, we synthesized hydrogels with comonomers PEG and the zwitterion phosphorylcholine (PC). Recent evidence suggests that stiff hydrogels elicit increased immune cell adhesion to hydrogels, which we attempted to reduce by increasing hydrogel hydrophilicity. Surprisingly, hydrogels with the highest amount of zwitterionic comonomer elicited the highest FBR. Lowering the hydrogel modulus (165 to 3 kPa), or PC content (20 to 0 wt %), mitigated this effect. A high density of macrophages was found at the surface of implants associated with a high FBR, and mass spectrometry analysis of the proteins adsorbed to these gels implicated extracellular matrix, immune response, and cell adhesion protein categories as drivers of macrophage recruitment. Overall, we show that modulus regulates macrophage adhesion to zwitterionic-PEG hydrogels, and demonstrate that chemical modifications to hydrogels should be studied in parallel with their physical properties to optimize implant design.

Pseudoreticulocytosis in a patient with hemoglobin Köln due to autofluorescent erythrocytes enumerated as reticulocytes by the Cell-Dyn 4000.

PubMed

Sato, Shoko; Hirayama, Koichi; Koyama, Akio; Harano, Teruo; Nagasawa, Toshiro; Ninomiya, Haruhiko

2004-01-01

Pseudoreticulocytosis in a 25-year-old female patient with hemoglobin Köln is reported. The abnormal hemoglobin, hemoglobin Köln (beta chain, Val98-->Met), had previously been confirmed in the patient at the age of 21 years, as well as in her mother, by polymerase chain reaction-based direct sequence analysis of the beta globin gene. The patient underwent splenectomy at the age of 22 years. On her admission to our hospital for treatment of an immunoglobulin A nephropathy, an analysis by an automated hematology analyzer, the Abbott Cell-Dyn 4000 (CD4000), reported a marked reticulocytosis. Staining by the Brecher method with new methylene blue indicated a moderate reticulocytosis (5.7%) of a lesser extent than that indicated by the CD4000 (51.1%). The frequencies of red blood cells (RBC) with Pappenheimer bodies (13.8%), Heinz bodies (32.7%), and Howell-Jolly bodies (0.3%) were increased. The CD4000 detects RBC with RNA fluorescently stained with CD4K530 as reticulocytes. Autofluorescence of RBC with hemoglobin Köln, as we demonstrated by flow cytometry and fluorescent microscopy, was considered to have caused the pseudoreticulocytosis on the fully automated reticulocyte enumeration by the CD4000.

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

PubMed

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

2015-01-01

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

Evaluation of a novel GRPR antagonist for prostate cancer PET imaging: [64Cu]-DOTHA2-PEG-RM26.

PubMed

Mansour, Nematallah; Paquette, Michel; Ait-Mohand, Samia; Dumulon-Perreault, Véronique; Guérin, Brigitte

2018-01-01

Gastrin releasing peptide receptors (GRPRs) are significantly over-expressed on a large proportion of prostate cancers making them prime candidates for receptor-mediated nuclear imaging by PET. Recently, we synthesized a novel bifunctional chelator (BFC) bearing hydroxamic acid arms (DOTHA 2 ). Here we investigated the potential of a novel DOTHA 2 -conjugated, 64 Cu-radiolabeled GRPR peptide antagonist, [D-Phe 6 -Sta 13 -Leu 14 -NH 2 ]bombesin(6-14) (DOTHA 2 -PEG-RM26) to visualize prostate tumors by PET imaging. DOTHA 2 -PEG-RM26 was conveniently and efficiently assembled on solid support. The compound was radiolabeled with 64 Cu and its affinity, stability, cellular uptake on PC3 prostate cancer cells were evaluated. The in vitro and in vivo behavior of [ 64 Cu]DOTHA 2 -PEG-RM26 was examined by PET imaging using human PC3 prostate cancer xenografts and its behavior was compared to that of the analogous [ 64 Cu]NOTA-PEG-RM26. The inhibition constant of nat Cu-DOTHA 2 -PEG-RM26 was in the low nanomolar range (0.68±0.19 nM). The [ 64 Cu]DOTHA 2 -PEG-RM26 conjugate was prepared with a labeling yield >95% and molar activity of 56±3 GBq/μmol after a 5-min room temperature labeling. [ 64 Cu]-DOTHA 2 -PEG-RM26 demonstrated rapid blood and renal clearance as well as a high tumor uptake. Small animal PET images confirmed high and specific uptake in PC3 tumor. Both [ 64 Cu]-DOTHA 2 -PEG-RM26 and [ 64 Cu]-NOTA-PEG-RM26 displayed similar tumor and normal tissue uptakes at early time point post injection. [ 64 Cu]-DOTHA 2 -PEG-RM26 allows visualization of prostate tumors by PET imaging. DOTHA 2 enables fast 64 Cu chelation under mild condition, and as such could be used advantageously for the development of other 64 Cu-labeled peptide-derived PET tracers. Copyright © 2017 Elsevier Inc. All rights reserved.

Controlled drug delivery through a novel PEG hydrogel encapsulated silica aerogel system.

PubMed

Giray, Seda; Bal, Tuğba; Kartal, Ayse M; Kızılel, Seda; Erkey, Can

2012-05-01

A novel composite material consisting of a silica aerogel core coated by a poly(ethylene) glycol (PEG) hydrogel was developed. The potential of this novel composite as a drug delivery system was tested with ketoprofen as a model drug due to its solubility in supercritical carbon dioxide. The results indicated that both drug loading capacity and drug release profiles could be tuned by changing hydrophobicity of aerogels, and that drug loading capacity increased with decreased hydrophobicity, while slower release rates were achieved with increased hydrophobicity. Furthermore, higher concentration of PEG diacrylate in the prepolymer solution of the hydrogel coating delayed the release of the drug which can be attributed to the lower permeability at higher PEG diacrylate concentrations. The novel composite developed in this study can be easily implemented to achieve the controlled delivery of various drugs and/or proteins for specific applications. Copyright © 2012 Wiley Periodicals, Inc.

PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional constipation: a double blind, randomised, controlled, multicentre trial

PubMed Central

Voskuijl, W; de Lorijn, F; Verwijs, W; Hogeman, P; Heijmans, J; Mäkel, W; Taminiau, J; Benninga, M

2004-01-01

Background: Recently, polyethylene glycol (PEG 3350) has been suggested as a good alternative laxative to lactulose as a treatment option in paediatric constipation. However, no large randomised controlled trials exist evaluating the efficacy of either laxative. Aims: To compare PEG 3350 (Transipeg: polyethylene glycol with electrolytes) with lactulose in paediatric constipation and evaluate clinical efficacy/side effects. Patients: One hundred patients (aged 6 months–15 years) with paediatric constipation were included in an eight week double blinded, randomised, controlled trial. Methods: After faecal disimpaction, patients <6 years of age received PEG 3350 (2.95 g/sachet) or lactulose (6 g/sachet) while children ⩾6 years started with 2 sachets/day. Primary outcome measures were: defecation and encopresis frequency/week and successful treatment after eight weeks. Success was defined as a defecation frequency ⩾3/week and encopresis ⩽1 every two weeks. Secondary outcome measures were side effects after eight weeks of treatment. Results: A total of 91 patients (49 male) completed the study. A significant increase in defecation frequency (PEG 3350: 3 pre v 7 post treatment/week; lactulose: 3 pre v 6 post/week) and a significant decrease in encopresis frequency (PEG 3350: 10 pre v 3 post/week; lactulose: 8 pre v 3 post/week) was found in both groups (NS). However, success was significantly higher in the PEG group (56%) compared with the lactulose group (29%). PEG 3350 patients reported less abdominal pain, straining, and pain at defecation than children using lactulose. However, bad taste was reported significantly more often in the PEG group. Conclusions: PEG 3350 (0.26 (0.11) g/kg), compared with lactulose (0.66 (0.32) g/kg), provided a higher success rate with fewer side effects. PEG 3350 should be the laxative of first choice in childhood constipation. PMID:15479678

PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional constipation: a double blind, randomised, controlled, multicentre trial.

PubMed

Voskuijl, W; de Lorijn, F; Verwijs, W; Hogeman, P; Heijmans, J; Mäkel, W; Taminiau, J; Benninga, M

2004-11-01

Recently, polyethylene glycol (PEG 3350) has been suggested as a good alternative laxative to lactulose as a treatment option in paediatric constipation. However, no large randomised controlled trials exist evaluating the efficacy of either laxative. To compare PEG 3350 (Transipeg: polyethylene glycol with electrolytes) with lactulose in paediatric constipation and evaluate clinical efficacy/side effects. One hundred patients (aged 6 months-15 years) with paediatric constipation were included in an eight week double blinded, randomised, controlled trial. After faecal disimpaction, patients <6 years of age received PEG 3350 (2.95 g/sachet) or lactulose (6 g/sachet) while children > or =6 years started with 2 sachets/day. Primary outcome measures were: defecation and encopresis frequency/week and successful treatment after eight weeks. Success was defined as a defecation frequency > or =3/week and encopresis < or =1 every two weeks. Secondary outcome measures were side effects after eight weeks of treatment. A total of 91 patients (49 male) completed the study. A significant increase in defecation frequency (PEG 3350: 3 pre v 7 post treatment/week; lactulose: 3 pre v 6 post/week) and a significant decrease in encopresis frequency (PEG 3350: 10 pre v 3 post/week; lactulose: 8 pre v 3 post/week) was found in both groups (NS). However, success was significantly higher in the PEG group (56%) compared with the lactulose group (29%). PEG 3350 patients reported less abdominal pain, straining, and pain at defecation than children using lactulose. However, bad taste was reported significantly more often in the PEG group. PEG 3350 (0.26 (0.11) g/kg), compared with lactulose (0.66 (0.32) g/kg), provided a higher success rate with fewer side effects. PEG 3350 should be the laxative of first choice in childhood constipation.

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

PubMed

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

2017-08-01

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

Ring and peg electrodes for minimally-Invasive and long-term sub-scalp EEG recordings.

PubMed

Benovitski, Y B; Lai, A; McGowan, C C; Burns, O; Maxim, V; Nayagam, D A X; Millard, R; Rathbone, G D; le Chevoir, M A; Williams, R A; Grayden, D B; May, C N; Murphy, M; D'Souza, W J; Cook, M J; Williams, C E

2017-09-01

Minimally-invasive approaches are needed for long-term reliable Electroencephalography (EEG) recordings to assist with epilepsy diagnosis, investigation and more naturalistic monitoring. This study compared three methods for long-term implantation of sub-scalp EEG electrodes. Three types of electrodes (disk, ring, and peg) were fabricated from biocompatible materials and implanted under the scalp in five ambulatory ewes for 3months. Disk electrodes were inserted into sub-pericranial pockets. Ring electrodes were tunneled under the scalp. Peg electrodes were inserted into the skull, close to the dura. EEG was continuously monitored wirelessly. High resolution CT imaging, histopathology, and impedance measurements were used to assess the status of the electrodes at the end of the study. EEG amplitude was larger in the peg compared with the disk and ring electrodes (p<0.05). Similarly, chewing artifacts were lower in the peg electrodes (p<0.05). Electrode impedance increased after long-term implantation particularly for those within the bone (p<0.01). Micro-CT scans indicated that all electrodes stayed within the sub-scalp layers. All pegs remained within the burr holes as implanted with no evidence of extrusion. Eight of 10 disks partially eroded into the bone by 1.0mm from the surface of the skull. The ring arrays remained within the sub-scalp layers close to implantation site. Histology revealed that the electrodes were encapsulated in a thin fibrous tissue adjacent to the pericranium. Overlying this was a loose connective layer and scalp. Erosion into the bone occurred under the rim of the sub-pericranial disk electrodes. The results indicate that the peg electrodes provided high quality EEG, mechanical stability, and lower chewing artifact. Whereas, ring electrode arrays tunneled under the scalp enable minimal surgical techniques to be used for implantation and removal. Copyright © 2017 Elsevier B.V. All rights reserved.

Ionic depletion at the crystalline Gibbs layer of PEG-capped gold nanoparticle brushes at aqueous surfaces

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

Wang, Wenjie; Zhang, Honghu; Mallapragada, Surya

In situ surface-sensitive x-ray diffraction and grazing incidence x-ray fluorescence spectroscopy (GIXFS) methods are combined to determine the ionic distributions across the liquid/vapor interfaces of thiolated-polyethylene-glycol–capped gold nanoparticle (PEG-AuNP) solutions. Induced by the addition of salts (i.e., Cs 2SO 4) to PEG-AuNPs solutions, two-dimensional hexagonal lattices of PEG-AuNPs form spontaneously at the aqueous surfaces, as is demonstrated by x-ray reflectivity and grazing incidence small-angle x-ray scattering. In conclusion, by taking advantage of element specificity with the GIXFS method, we find that the cation Cs + concentration at the crystalline film is significantly reduced in parts of the PEG-AuNP film comparedmore » with that in the bulk.« less

Electrochemical and XPS study of LiFePO4 cathode nanocomposite with PPy/PEG conductive network

NASA Astrophysics Data System (ADS)

Fedorková, A.; Oriňáková, R.; Oriňák, A.; Kupková, M.; Wiemhöfer, H.-D.; Audinot, J. N.; Guillot, J.

2012-08-01

High performance PPy/PEG-LiFePO4 nanocomposites as cathode materials were synthesized by solvothermal method and simple chemical oxidative polymerization of pyrrole (Py) monomer on the surface of LiFePO4 particles. The samples were characterized by scanning electron microscope (SEM), energy dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectrometry (XPS) and charge-discharge tests. PPyPEG hybrid layers decrease particle to particle contact resistance while the impedance measurements confirmed that the coating of PPy-PEG significantly decreases the charge transfer resistance of the electrode material. The initial discharge capacities of this sample at C/5 and 1C are 150 and 128 mAh/g, respectively. The results show that PPy/PEGLiFePO4 composites are more effective than bare LiFePO4 as cathode material.

Ionic depletion at the crystalline Gibbs layer of PEG-capped gold nanoparticle brushes at aqueous surfaces

DOE PAGES

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

2017-12-14

In situ surface-sensitive x-ray diffraction and grazing incidence x-ray fluorescence spectroscopy (GIXFS) methods are combined to determine the ionic distributions across the liquid/vapor interfaces of thiolated-polyethylene-glycol–capped gold nanoparticle (PEG-AuNP) solutions. Induced by the addition of salts (i.e., Cs 2SO 4) to PEG-AuNPs solutions, two-dimensional hexagonal lattices of PEG-AuNPs form spontaneously at the aqueous surfaces, as is demonstrated by x-ray reflectivity and grazing incidence small-angle x-ray scattering. In conclusion, by taking advantage of element specificity with the GIXFS method, we find that the cation Cs + concentration at the crystalline film is significantly reduced in parts of the PEG-AuNP film comparedmore » with that in the bulk.« less

Lack of lasting effectiveness of PEG 3350 laxative treatment of constipation.

PubMed

Tran, Lily C; Di Palma, Jack A

2005-08-01

PEG 3350 (MiraLax, Braintree Laboratories Inc., Braintree, MA) 17 g daily has been shown to be safe and effective in a 14-day trial for constipation. This present investigation was designed to extend the treatment and safety experience with PEG 3350 and to evaluate any lasting effectiveness during a 30-day post-treatment observation period. Study subjects met Rome II criteria for constipation and reported <3 bowel movements a week. They were treated with PEG 3350 17 g daily for 14 days. Treatment efficacy was defined by resolution of constipation symptoms as determined by the Rome II and stool frequency definitions during the treatment period. Fifty healthy constipated subjects formed the study group. There were 42 females and 8 males. Mean age was 52 +/- 15.5 years (+/-SD). Symptom duration was 22.6 +/- 16.7 months (+/-SD). At baseline, all had <3 bowel movements a week and met Rome II criteria. Two were lost to follow-up. Two took enemas or laxatives and 2 discontinued active treatment because of "gas" and were considered treatment failures. At the end of 14 days, 40 of 48 (83.3%) had >3 stools in the last week and no longer met Rome criteria. Thirty-two of 45 (71.1%) reported satisfaction with the first bowel movement after initiating treatment. Thirty days after active treatment, 29 of 47 (61.7%) responded that they needed laxative treatment. PEG 3350 relieved constipation in most treated study subjects. During a 30-day post-treatment observation period, 29 of 47 (61.7%) had additional constipation treatment interventions.

PVP and PEG doped CuO nanoparticles are more biologically active: Antibacterial, antioxidant, antidiabetic and cytotoxic perspective.

PubMed

Javed, Rabia; Ahmed, Madiha; Haq, Ihsan Ul; Nisa, Sobia; Zia, Muhammad

2017-10-01

Search for biologically active nanoparticles is prerequisite for biomedical applications. CuO nanoparticles synthesized by co-precipitation method are capped by polyethylene-glycol (PEG) and polyvinyl-pyrrolidone (PVP) on the surface by simple adsorption. Physical and chemical properties carried out by SEM, XRD and FTIR confirm nanometer in size and efficient capping of PVP and PEG on CuO NPs. Biological assays reveal higher activities of CuO-PEG and CuO-PVP as compared to the uncapped CuO nanoparticles. CuO-PEG shows better antitumor activity against Streptomyces as compared with CuO-PVP and CuO NPs. Both the capped NPs are significantly active for α-amylase inhibition assay. CuO-PVP demonstrates significantly better activity against bacterial strains followed by CuO-PEG and uncapped CuO. PVP coated CuO NPs also shows strong DPPH based free radical scavenging activity, total reducing power potential, total antioxidative potential and also carries flavonoid and phenolics properties determines to querecetin and gallic acid equivalence, respectively. It can be concluded that PVP and PEG capped CuO NPs are more capable to be used in biomedical applications as drug and diagnostic carrier molecules. Copyright © 2017 Elsevier B.V. All rights reserved.

PEG Molecular Net-Cloth Grafted on Polymeric Substrates and Its Bio-Merits

NASA Astrophysics Data System (ADS)

Zhao, Changwen; Lin, Zhifeng; Yin, Huabing; Ma, Yuhong; Xu, Fujian; Yang, Wantai

2014-05-01

Polymer brushes and hydrogels are sensitive to the environment, which can cause uncontrolled variations on their performance. Herein, for the first time, we report a non-swelling ``PEG molecular net-cloth'' on a solid surface, fabricated using a novel ``visible light induced surface controlled graft cross-linking polymerization'' (VSCGCP) technique. Via this method, we show that 1) the 3D-network structure of the net-cloth can be precisely modulated and its thickness controlled; 2) the PEG net-cloth has excellent resistance to non-specific protein adsorption and cell adhesion; 3) the mild polymerization conditions (i.e. visible light and room temperature) provided an ideal tool for in situ encapsulation of delicate biomolecules such as enzymes; 4) the successive grafting of reactive three-dimensional patterns on the PEG net-cloth enables the creation of protein microarrays with high signal to noise ratio. Importantly, this strategy is applicable to any C-H containing surface, and can be easily tailored for a broad range of applications.

Composite porous scaffold of PEG/PLA support improved bone matrix deposition in vitro compared to PLA-only scaffolds.

PubMed

Bhaskar, Birru; Owen, Robert; Bahmaee, Hossein; Wally, Zena; Sreenivasa Rao, Parcha; Reilly, Gwendolen C

2018-05-01

Controllable pore size and architecture are essential properties for tissue-engineering scaffolds to support cell ingrowth colonization. To investigate the effect of polyethylene glycol (PEG) addition on porosity and bone-cell behavior, porous polylactic acid (PLA)-PEG scaffolds were developed with varied weight ratios of PLA-PEG (100/0, 90/10, 75/25) using solvent casting and porogen leaching. Sugar 200-300 µm in size was used as a porogen. To assess scaffold suitability for bone tissue engineering, MLO-A5 murine osteoblast cells were cultured and cell metabolic activity, alkaline phosphatase (ALP) activity and bone-matrix production determined using (alizarin red S staining for calcium and direct red 80 staining for collagen). It was found that metabolic activity was significantly higher over time on scaffolds containing PEG, ALP activity and mineralized matrix production were also significantly higher on scaffolds containing 25% PEG. Porous architecture and cell distribution and penetration into the scaffold were analyzed using SEM and confocal microscopy, revealing that inclusion of PEG increased pore interconnectivity and therefore cell ingrowth in comparison to pure PLA scaffolds. The results of this study confirmed that PLA-PEG porous scaffolds support mineralizing osteoblasts better than pure PLA scaffolds, indicating they have a high potential for use in bone tissue engineering applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1334-1340, 2018. © 2018 Wiley Periodicals, Inc.

Clinical trial: single- and multiple-dose pharmacokinetics of polyethylene glycol (PEG-3350) in healthy young and elderly subjects.

PubMed

Pelham, R W; Nix, L C; Chavira, R E; Cleveland, M Vb; Stetson, P

2008-07-01

The pharmacokinetics of polyethylene glycol 3350 (PEG-3350) have not been fully described because of lack of a sufficiently sensitive analytical method. To describe the pharmacokinetics of PEG-3350 in humans. A highly sensitive, high performance liquid chromatography with mass spectrometry (HPLC/MS/MS) method was developed for PEG-3350 in urine, plasma and faeces with quantification limits of 30 ng/mL, 100 ng/mL and 500 microg/g respectively. Noncompartmental pharmacokinetics methods were used and the effects of gender, age, renal status and dosing frequency were examined after the oral administration of 17 g to healthy volunteers. Peak PEG-3350 plasma concentrations occurred at 2-4 h and declined to nonquantifiable levels usually within 18 h after single and multiple doses, with a half-life of about 4-6 h. Steady state was reached within 5 days of dosing. Mean urinary excretion of the administered dose ranged from 0.19% to 0.25%. Age, gender or mild kidney impairment did not alter the pharmacokinetics of PEG-3350. Mean faecal excretion of the administered dose was 93% in young subjects. For the first time, a highly sensitive assay allowed comprehensive pharmacokinetics studies of PEG-3350 in humans. These studies confirmed that orally administered PEG-3350 is minimally absorbed, rapidly excreted and primarily eliminated via faeces.

Synthetic PEG Hydrogel for Engineering the Environment of Ovarian Follicles.

PubMed

Mendez, Uziel; Zhou, Hong; Shikanov, Ariella

2018-01-01

The functional unit within the ovary is the ovarian follicle, which is also a morphological unit composed of three basic cell types: the oocyte, granulosa, and theca cells. Similar to human ovarian follicles, mouse follicles can be isolated from their ovarian environment and cultured in vitro to study folliculogenesis, or follicle development for days or weeks. Over the course of the last decade, follicle culture in a three-dimensional (3D) environment exponentially improved the outcomes of in vitro folliculogenesis. Follicle culture in 3D environments preserves follicle architecture and promotes the cross talk between cells in the follicle. Hydrogels, such as polyethylene glycol (PEG), have been used for various physiological systems for regenerative purposes because they provide a 3D environment similar to soft tissues, allow diffusion of nutrients, and can be readily modified to present biological signals, including cell adhesion ligands and proteolytic degradation facilitated by enzymes secreted by the encapsulated cells. This chapter outlines the application of PEG hydrogels to the follicle culture, including the procedures to isolate, encapsulate, and culture mouse ovarian follicles. The tunable properties of PEG hydrogels support co-encapsulation of ovarian follicles with somatic cells, which further promote follicle survival and growth in vitro through paracrine and juxtacrine interactions.

Use of Powder PEG-3350 as a Sole Bowel Preparation

PubMed Central

Arora, Manish

2008-01-01

Objective: To assess the efficacy of low-volume powder polyethylene glycol (PEG)-3350 as a sole bowel preparation for colonoscopy. Methods: This case series examined 245 consecutive patients (a mixture of inpatients and outpatients undergoing screening colonoscopy) at a hospital endoscopy center over a 2-year period. The patients received powder PEG-3350 in the amount of 204 g dissolved in 32 oz of water and taken in 3 divided doses 1 hour apart with 8 oz of water in between each dose. Colon preparation scores (CPS) were used to assess the quality of colon cleansing. The results obtained from the 245 patients were collated and compared to those of patients receiving sodium phosphate, the historical control. Results: The mean CPS was calculated to be 3.43, with a standard deviation of 1.12. Of the 245 patients, 92 were scored with a grade of 4, and 5 patients had incomplete colonoscopies secondary to failure of bowel preparation (CPS=0). Among the remaining patients, 22 and 26 were graded as poor (CPS=1) or fair (CPS=2) bowel preparations, respectively. Conclusion: The low-volume powder PEG-3350 formula used in our case series showed effective colon cleansing and may be considered for use as a sole bowel preparation. PMID:21960925

Modification of titanium surfaces by adding antibiotic-loaded PHB spheres and PEG for biomedical applications.

PubMed

Rodríguez-Contreras, Alejandra; Marqués-Calvo, María Soledad; Gil, Francisco Javier; Manero, José María

2016-08-01

Novel researches are focused on the prevention and management of post-operative infections. To avoid this common complication of implant surgery, it is preferable to use new biomaterials with antibacterial properties. Therefore, the aim of this work is to develop a method of combining the antibacterial properties of antibiotic-loaded poly(3-hydroxybutyrate) (PHB) nano- and micro-spheres and poly(ethylene glycol) (PEG) as an antifouling agent, with titanium (Ti), as the base material for implants, in order to obtain surfaces with antibacterial activity. The Ti surfaces were linked to both PHB particles and PEG by a covalent bond. This attachment was carried out by firstly activating the surfaces with either Oxygen plasma or Sodium hydroxide. Further functionalization of the activated surfaces with different alkoxysilanes allows the reaction with PHB particles and PEG. The study confirms that the Ti surfaces achieved the antibacterial properties by combining the antibiotic-loaded PHB spheres, and PEG as an antifouling agent.

Influence of PEG coating on optical and thermal response of gold nanoshperes and nanorods

NASA Astrophysics Data System (ADS)

Chen, Qin; Ren, Yatao; Qi, Hong; Ruan, Liming

2018-06-01

PEGylation is widely applied as a surface modification method for nanoparticles in biomedical applications to improve their biological properties, including biocompatibility and immunogenicity. In most of its biomedical applications, nanoparticles are served as optical or thermal contrast agents. Therefore, the impact of poly (ethylene glycol) (PEG) coating thickness on the optical and thermal properties of nanoparticles needs to be further investigated. In the present work, we studied two kinds of commonly used nanoparticles, including nanosphere and nanorod. The temperature and electric fields are obtained for nanoparticles with different PEG coating thicknesses. It is found that the change of PEG coating thickness on gold nanospheres only has impact on the absolute value of maximum absorption and scattering efficiencies, which barely influences the LSPR wavelength λmax and other optical and thermal characteristics. In contrast, for nanorod, the maximum efficiencies are barely influenced by the variation of PEG coating thickness. On the other hand, the localized surface plasmon resonance wavelength has an evident red shift with the increasing of PEG coating thickness. The maximum absorption efficiency is a way to evaluate the energy dissipation rate, which decides the scale of the heat source induced by nanoparticles. These findings are crucial for the accurate prediction of optical and thermal properties of nanoparticles in biomedical application. The present work also presents a possible way to manipulate the optical and thermal behaviors of nanoparticles in the application of biomedicine without changing the morphology of nanoparticles.

75 FR 44725 - Airworthiness Directives; Pratt & Whitney PW4000 Series Turbofan Engines; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-29

... Engineer, Engine Certification Office, FAA, Engine and Propeller Directorate, 12 New England Executive Park..., Massachusetts, on July 23, 2010. Francis A. Favara, Manager, Engine and Propeller Directorate, Aircraft... PW4000 Series Turbofan Engines; Correction AGENCY: Federal Aviation Administration (FAA), DOT. ACTION...

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

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

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

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

Effect of PEG-PDMAEMA Block Copolymer Architecture on Polyelectrolyte Complex Formation with Heparin.

PubMed

Välimäki, Salla; Khakalo, Alexey; Ora, Ari; Johansson, Leena-Sisko; Rojas, Orlando J; Kostiainen, Mauri A

2016-09-12

Heparin is a naturally occurring polyelectrolyte consisting of a sulfated polysaccharide backbone. It is widely used as an anticoagulant during major surgical operations. However, the associated bleeding risks require rapid neutralization after the operation. The only clinically approved antidote for heparin is protamine sulfate, which is, however, ineffective against low molecular weight heparin and can cause severe adverse reactions in patients. In this study, the facile synthesis of cationic-neutral diblock copolymers and their effective heparin binding is presented. Poly(ethylene glycol)-poly(2-(dimethylamino)ethyl methacrylate) (PEG-PDMAEMA) block copolymers were synthesized in two steps via atom-transfer radical polymerization (ATRP) using PEG as a macroinitiator. Solution state binding between heparin and a range of PEG-PDMAEMA block copolymers and one homopolymer was studied with dynamic light scattering and methylene blue displacement assay. Also in vitro binding in plasma was studied by utilizing a chromogenic heparin anti-Xa assay. Additionally, quartz crystal microbalance and multiparametric surface plasmon resonance were used to study the surface adsorption kinetics of the polymers on a heparin layer. It was shown that the block copolymers and heparin form electrostatically bound complexes with varying colloidal properties, where the block lengths play a key role in controlling the heparin binding affinity, polyelectrolyte complex size and surface charge. With the optimized polymers (PEG114PDMAEMA52 and PEG114PDMAEMA100), heparin could be neutralized in a dose-dependent manner, and bound efficiently into small neutral complexes, with a hydrodynamic radius less than 100 nm. These complexes had only a limited effect on cell viability. Based on these studies, our approach paves the way for the development of new polymeric heparin binding agents.

Ethylene Glycol - Polyethylene Glycol (EG-PEG) Mixtures: Infrared Spectra Wavelet Cross-Correlation Analysis.

PubMed

Caccamo, Maria Teresa; Magazù, Salvatore

2017-03-01

Infrared spectra were collected on mixtures of ethylene glycol (EG) and polyethylene glycol 600 (PEG600) as a function of weight fraction from pure EG to pure PEG600. In this paper, it will be shown that while the OH vibrational contribution drastically reduces its center frequency from 3450 cm -1 to 3300 cm -1 in the weight fraction range 0-25%, the displacement of the mixture spectral features of the mixtures from ideal behavior, i.e., in the absence of interaction, shows the presence of a non-ideal mixing process. Furthermore, wavelet cross-correlation analysis of the registered pairs of spectra and of the intramolecular O-H stretching contributions reveals how the addition of a small amount of pure EG to PEG600 dramatically influences the structural properties of the polymeric matrix, owing to an increase the intermolecular connectivity. In particular, the wavelet cross-correlation parameters, evaluated between each pair of the registered data as a function of weight fraction, in a linear-logarithmic plot, reveals an inflection point for a weight fraction of about 25% of EG, which confirms that, within the three-dimensional networks of hydrogen-bonded EG-PEG600 molecules, a key role is played by EG in determining an increase in the hydrogen-bond network density.

Structural, spectroscopic and anti-microbial inspection of PEG capped ZnO nanoparticles for biomedical applications

NASA Astrophysics Data System (ADS)

Meshram, J. V.; Koli, V. B.; Kumbhar, S. G.; Borde, L. C.; Phadatare, M. R.; Pawar, S. H.

2018-04-01

Zinc oxide (ZnO) nanoparticles (NPs) have a wide range of biomedical applications. Present study demonstrates the new methodology in sol-gel technology for synthesizing Polyethylene glycol (PEG) capped ZnO NPs and its size effect on anti-microbial activity. The reaction time was increased from 1 h to 5 h for the synthesis of ZnO NPs at 130 °C. The size of PEG capped ZnO NPs is increased from 10 to 84 nm by increasing the reaction upto 5 h. The x-ray diffraction studies and transmission electron microscopy analysis reveals the phase purity and hexagonal wurtzite crystal structure with uniform PEG capping on the surface of ZnO NPs. UV–visible spectroscopy exhibits the peak at 366 nm which is attributed to ZnO NPs. No adverse effect is observed in case of absorbance spectroscopy. Further, Fourier transforms infrared spectroscopy and thermo gravimetric analysis depicts the adsorption of PEG molecules on the ZnO NPs surface. The anti-microbial activities for both Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria were studied by optical density (OD) mesurement. The remarkable anti-microbial activity was observed for PEG capped ZnO NPs synthesized at 1 h reaction time showing higher activity in comparison with that synthesized from 2 h to 5 h reaction time. The microbial growth was found to be inhibited after 10 h OD measurement for both the bacteria. The anti-microbial activity may be attributed to the generation of ROS and H2O2. However, these generated species plays a vital role in inhibition of microbial growth. Hence, PEG capped ZnO NPs has promising biomedical applications.

Shedding PEG Palisade by Temporal Photostimulation and Intracellular Reducing Milieu for Facilitated Intracellular Trafficking and DNA Release.

PubMed

Wang, Tieyan; Chen, Qixian; Lu, Hongguang; Li, Wei; Li, Zaifen; Ma, Jianbiao; Gao, Hui

2016-08-17

The dilemma of poly(ethylene glycol) surface modification (PEGylation) inspired us to develop an intracellularly sheddable PEG palisade for synthetic delivery systems. Here, we attempted to conjugate PEG to polyethylenimine (PEI) through tandem linkages of disulfide-bridge susceptible to cytoplasmic reduction and an azobenzene/cyclodextrin inclusion complex responsive to external photoirradiation. The subsequent investigations revealed that facile PEG detachment could be achieved in endosomes upon photoirradiation, consequently engendering exposure of membrane-disruptive PEI for facilitated endosome escape. The liberated formulation in the cytosol was further subjected to complete PEG detachment relying on disulfide cleavage in the reductive cytosol, thus accelerating dissociation of electrostatically assembled PEI/DNA polyplex to release DNA by means of polyion exchange reaction with intracellularly charged species, ultimately contributing to efficient gene expression.

Clinical Trial of AC105 (Mg/PEG) for Treatment of Acute Spinal Cord Injury (SCI). Phase 2

DTIC Science & Technology

2013-10-01

glycol with a molecular weight of 3350 Daltons ( PEG 3350 ), is manufactured by Dow Chemical Company and complies with NF, FCC and EurPh requirements...Mg/ PEG ) for Treatment of Acute Spinal Cord Injury (SCI) PRINCIPAL INVESTIGATOR: Andrew Blight, PhD RECIPIENT: Acorda Therapeutics...of AC105 (Mg/ PEG ) for Treatment of Acute Spinal Cord Injury (SCI) 5b. GRANT NUMBER W81XWH-12-2 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d

Effect of spatial distribution of wax and PEG-isocyanate on the morphology and hydrophobicity of starch films.

PubMed

Muscat, Delina; Adhikari, Raju; Tobin, Mark J; McKnight, Stafford; Wakeling, Lara; Adhikari, Benu

2014-10-13

This study proposes a novel method for improving surface hydrophobicity of glycerol plasticized high amylose (HAG) films. We used polyethylene glycol isocyanate (PEG-iso) crosslinker to link HAG and three natural waxes (beeswax, candelilla wax and carnauba wax) to produce HAG+wax+PEG-iso films. The spatial distributions of wax and PEG-iso across the thickness of these films were determined using Synchrotron-based Fourier transform infrared spectroscopy. The hydrophobicity and surface morphology of the films were determined using contact angle (CA) and scanning electron microscopic measurements, respectively. The distribution patterns of wax and the PEG-iso across the thickness of the film, and the nature of crystalline patterns formed on the surface of these films were found to be the key factors affecting surface hydrophobicity. The highest hydrophobicity (CA >90°) was created when the PEG-iso was primarily distributed in the interior of the films and a hierarchical circular pinnacle structure of solidified wax was formed on the surface. Copyright © 2014 Elsevier Ltd. All rights reserved.

Toxicity Evaluation and Anti-Tumor Study of Docetaxel Loaded mPEG-Polyester Micelles for Breast Cancer Therapy.

PubMed

Tan, Li Wei; Ma, Bu Yun; Zhao, Qian; Zhang, Lan; Chen, Li Juan; Peng, Jin Rong; Qian, Zhi Yong

2017-04-01

In this work, docetaxel (DTX) was encapsulated in monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) micelles and monomethoxy poly(ethylene glycol)-poly(D, L-lactic acid) (mPEG-PLA) micelles, respectively. For the further application, the acute/genetic toxicity evaluation and pharmacokinetic/pharmacodynamic study of the two kinds of micellar nanomedicines were performed. In the study of anticancer activity in vitro and in vivo, DTX micelles showed better tumorgrowth inhibition than free DTX. The pharmacokinetic and tissue distribution studies showed that the DTX incorporated in micelles (especially in DTX-mPEG-PCL) retained significantly higher concentration in plasma and tumor tissue compared with free DTX. The acute toxicity and genotoxicity studies indicated that DTX micelles were safer than the docetaxel injection in cancer therapy and DTX-mPEG-PCL had less damage to DNA than DTX-mPEG-PLA. So the micelles had a pronounced effect on reducing acute toxicity and genotoxicity of docetaxel. In conclusion, DTX micelles were efficient and safe on breast carcinoma chemotherapy.

Vitamin D in addition to peg-interferon-alpha/ribavirin in chronic hepatitis C virus infection: ANRS-HC25-VITAVIC study.

PubMed

Terrier, Benjamin; Lapidus, Nathanael; Pol, Stanislas; Serfaty, Lawrence; Ratziu, Vlad; Asselah, Tarik; Thibault, Vincent; Souberbielle, Jean-Claude; Carrat, Fabrice; Cacoub, Patrice

2015-05-14

To investigate if correction of hypovitaminosis D before initiation of Peg-interferon-alpha/ribavirin (PegIFN/RBV) therapy could improve the efficacy of PegIFN/RBV in previously null-responder patients with chronic genotype 1 or 4 hepatitis C virus (HCV) infection. Genotype 1 or 4 HCV-infected patients with null response to previous PegIFN/RBV treatment and with hypovitaminosis D (< 30 ng/mL) prospectively received cholecalciferol 100000 IU per week for 4 wk [from week -4 (W-4) to W0], followed by 100000 IU per month in combination with PegIFN/RBV for 12 mo (from W0 to W48). The primary outcome was the rate of early virological response defined by an HCV RNA < 12 IU/mL after 12 wk PegIFN/RBV treatment. A total of 32 patients were included, 19 (59%) and 13 (41%) patients were HCV genotype 1 and 4, respectively. The median baseline vitamin D level was 15 ng/mL (range: 7-28). In modified intention-to-treat analysis, 29 patients who received at least one dose of PegIFN/RBV were included in the analysis. All patients except one normalized their vitamin D serum levels. The rate of early virologic response was 0/29 (0%). The rate of HCV RNA < 12 IU/mL after 24 wk of PegIFN/RBV was 1/27 (4%). The safety profile was favorable. Addition of vitamin D to PegIFN/RBV does not improve the rate of early virologic response in previously null-responders with chronic genotype 1 or 4 HCV infection.

Biomedical applications of SPION@APTES@PEG-folic acid@carboxylated quercetin nanodrug on various cancer cells

NASA Astrophysics Data System (ADS)

Akal, Z. Ü.; Alpsoy, L.; Baykal, A.

2016-08-01

In this study, carboxylated quercetin (CQ) was conjugated to superparamagnetic iron oxide nanoparticles (SPIONs) which were modified by (3-aminopropyl) triethoxysilane (APTES), Folic acid (FA) and carboxylated Polyethylene glycol (PEG); (SPION@APTES@FA-PEG@CQ), nanodrug has been synthesized via polyol and accompanying by various chemical synthesis routes. The characterization of the final product was done via X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Thermal gravimetric analysis (TGA), Transmission electron spectroscopy (TEM) and Vibrating sample magnetometer (VSM). Its cytotoxic and apoptotic activities on over expressed folic acid receptor (FR +) (MCF-7, HeLa) and none expressed folic acid receptor (FR-) (A549) cancer cell lines were determined by using MTT assay, Real-Time Cell Analysis, TUNEL assay, Annexin assay and RT-PCR analysis for Caspase3/7 respectively. SPION@APTES@FA-PEG@CQ nanodrug showed higher cytotoxicity against HeLa and MCF-7 cell lines as compared with A549 cell line. Moreover, SPION@APTES@FA-PEG@CQ nanodrug also caused higher apoptotic and necrotic effects in 100 μg/mL HeLa and MCF-7 cells than A549 cells. The findings showed that SPION@APTES@FA-PEG@CQ nanodrug has cytotoxic, apoptotic and necrotic effects on HeLa and MCF-7 which are FR over expressed cell lines and can be potentially used for the delivery of quercetin to cervical and breast cancer cells.

Effect of Modified Nanoclay Composite on Blended PVDF/PEG Electrolyte Membranes for Fuel Cell Applications

NASA Astrophysics Data System (ADS)

Bahavan Palani, P.; Sainul Abidin, K.; Kannan, R.; Rajashabala, S.

This research work describes the fabrication of polymer blend nanocomposite membranes using the solution casting method. These membranes were fabricated with Poly (Vinylidene Fluoride) (PVdF) as host, Poly (Ethylene Glycol) (PEG) in steps of 2wt.% as blending polymer and Montmorillonite (MMT) nanoclay particles in steps of 3wt.% which were used as received. The protonated MMT was synthesized through an ion exchange process with column chromatographic technique. The prepared membrane’s performance was investigated using different characterization techniques of Thermo Gravimetric Analysis (TGA), Fourier Transform Infrared Spectroscopy (FT-IR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), water uptake, IEC and electrochemical impedance spectroscopy. Thermal stability was decreased while adding PEG into PVDF but it is controlled with the addition of MMT on PVDF/PEG blend matrix. Moreover, It is noticed that, the increase of water uptake, IEC by the increasing additive concentration of PEG and MMT. XRD studies reveal the increased amorphous phase with uniform exfoliation of nanoclay particles. The highest proton conductivity value of 0.127S cm‑1 is obtained with 9wt.% of MMT in the PVdF/PEG/MMT composite membranes at room temperature with 100% Relative Humid (RH) condition and 10 V.% of sulfonation. The blended nanocomposite membranes fulfill the requirements of proton exchange membrane for fuel cell application.

Antifouling activities of β-cyclodextrin stabilized peg based silver nanocomposites

NASA Astrophysics Data System (ADS)

Punitha, N.; Saravanan, P.; Mohan, R.; Ramesh, P. S.

2017-01-01

Self-polishing polymer composites which release metal biocide in a controlled rate have been widely used in the design of antimicrobial agents and antifouling coatings. The present work focuses on the environmental friendly green synthesis of PEG based SNCs and their application to biocidal activity including marine biofouling. Biocompatible polymer β-CD and adhesive resistance polymer PEG were used to functionalize the SNPs and the as synthesized SNCs exhibit excellent micro fouling activities. The structural and optical properties were confirmed by XRD and UV-visible techniques respectively. The particle surface and cross sectional characteristics were examined by SEM-EDS, HR-TEM, AFM and FTIR. The surface potential was evaluated using ZP analysis and assessment of antibiofouling property was investigated using static immersion method.

SAVY-4000 Surveillance and Life Extension Program Fiscal Year 2013 Annual Report

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

Stone, Timothy A.; Blair, Michael W.; Weis, Eric

2014-03-03

The Packaging Surveillance Program section of the DOE M441.1-1 /sup>1, Nuclear Material Packaging Manual (DOE, 2008) requires DOE contractors to “ensure that a surveillance program is established and implemented to ensure the nuclear material storage package continues to meet its design criteria.” In order to ensure continuing safe storage of nuclear material and the maximization of risk reduction, TA-55 has established a Surveillance Program to ensure storage container integrity for operations within its specified design life. The LANL SAVY-4000 Field Surveillance Plan2 defines the near-term field surveillance plan for SAVY-4000 containers as required by the Manual. A long-term surveillance planmore » will be established based on the results of the first several years of surveillance and the results of the lifetime extension studies as defined in the Accelerated Aging Plan3. This report details progress in positioning the Surveillance Program for successful implementation in FY14 and status of the Design Life Extension Program in terms of its implementation and data collection for FY13.« less

Wastewater treatment by sonophotocatalysis using PEG modified TiO2 film in a circular Photocatalytic-Ultrasonic system.

PubMed

Hu, Xiaohong; Zhu, Qi; Gu, Zhibin; Zhang, Nan; Liu, Na; Stanislaus, Mishma S; Li, Dawei; Yang, Yingnan

2017-05-01

TiO 2 photocatalyst film recently has been utilized as the potential candidate for the wastewater treatment, due to its high stability and low toxicity. In order to further increase the photocatalytic ability and stability, different molecular weight of polyethylene glycol (PEG) were used to modify TiO 2 structure to synthesize porous thin film used in the developed Photocatalytic-Ultrasonic system in this work. The results showed that PEG2000 modified TiO 2 calcinated under 450°C for 2h exhibited the highest photocatalytic activity, attributed to the smallest crystallite size and optimal particle size. Over 95.0% of rhodamine B (Rh B) was photocatalytically degraded by optimized PEG 2000 -TiO 2 film after 60min of UV irradiation, while only about 50.8% of Rh B was decolored over pure TiO 2 film. Furthermore, optimized PEG 2000 -TiO 2 film was used in a circular Photocatalytic-Ultrasonic system, and the obtained synergy (0.6519) of sonophotocatalysis indicated its extremely high efficiency for Rh B degradation. In this Photocatalytic-Ultrasonic system, larger amount of PEG 2000 -TiO 2 coated glass beads, stronger ultrasonic power and longer experimental time could result to higher degradation efficiency of Rh B. In addition, repetitive experiments showed that about 97.2% of Rh B were still degraded in the fifth experiment by sonophotocatalysis using PEG 2000 -TiO 2 film. Therefore, PEG 2000 -TiO 2 film used in Photocatalytic-Ultrasonic system has promising potential for wastewater treatment, due to its excellent photocatalytic activity and high stability. Copyright © 2016 Elsevier B.V. All rights reserved.

Inhibition mechanism of P-glycoprotein mediated efflux by mPEG-PLA and influence of PLA chain length on P-glycoprotein inhibition activity.

PubMed

Li, Wenjing; Li, Xinru; Gao, Yajie; Zhou, Yanxia; Ma, Shujin; Zhao, Yong; Li, Jinwen; Liu, Yan; Wang, Xinglin; Yin, Dongdong

2014-01-06

The present study aimed to investigate the effect of monomethoxy poly(ethylene glycol)-block-poly(D,L-lactic acid) (mPEG-PLA) on the activity of P-glycoprotein (P-gp) in Caco-2 cells and further unravel the relationship between PLA chain length in mPEG-PLA and influence on P-gp efflux and the action mechanism. The transport results of rhodamine 123 (R123) across Caco-2 cell monolayers suggested that mPEG-PLA unimers were responsible for its P-gp inhibitory effect. Furthermore, transport studies of R123 revealed that the inhibitory potential of P-gp efflux by mPEG-PLA analogues was strongly correlated with their structural features and showed that the hydrophilic mPEG-PLA copolymers with an intermediate PLA chain length and 10.20 of hydrophilic-lipophilic balance were more effective at inhibiting P-gp efflux in Caco-2 cells. The fluorescence polarization measurement results ruled out the plasma membrane fluidization as a contributor for inhibition of P-gp by mPEG-PLA. Concurrently, mPEG-PLA inhibited neither basal P-gp ATPase (ATP is adenosine triphosphate) activity nor substrate stimulated P-gp ATPase activity, suggesting that mPEG-PLA seemed not to be a substrate of P-gp and a competitive inhibitor. No evident alteration in P-gp surface level was detected by flow cytometry upon exposure of the cells to mPEG-PLA. The depletion of intracellular ATP, which was likely to be a result of partial inhibition of cellular metabolism, was directly correlated with inhibitory potential for P-gp mediated efflux by mPEG-PLA analogues. Hence, intracellular ATP-depletion appeared to be possible explanation to the inhibition mechanism of P-gp by mPEG-PLA. Taken together, the establishment of a relationship between PLA chain length and impact on P-gp efflux activity and interpretation of action mechanism of mPEG-PLA on P-gp are of fundamental importance and will facilitate future development of mPEG-PLA in the drug delivery area.

δ Scuti-type pulsation in the hot component of the Algol-type binary system BG Peg

NASA Astrophysics Data System (ADS)

Şenyüz, T.; Soydugan, E.

2014-02-01

In this study, 23 Algol-type binary systems, which were selected as candidate binaries with pulsating components, were observed at the Çanakkale Onsekiz Mart University Observatory. One of these systems was BG Peg. Its hotter component shows δ Scuti-type light variations. Physical parameters of BG Peg were derived from modelling the V light curve using the Wilson-Devinney code. The frequency analysis shows that the pulsational component of the BG Peg system pulsates in two modes with periods of 0.039 and 0.047 d. Mode identification indicates that both modes are most likely non-radial l = 2 modes.

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

PubMed

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

2016-08-17

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

Physicochemical characterization of 3,6-diHydroxyflavone binding BSA immobilized on PEG-coated silver nanoparticles

NASA Astrophysics Data System (ADS)

Voicescu, Mariana; Ionescu, Sorana; Calderon-Moreno, Jose M.; Nistor, Cristina L.

2017-02-01

Studies based on silver nanoparticles (SNPs) and polyethylene glycols (PEGs) are mainly in the pharmaceutical field, with PEG as good "vehicle" to transport protein-based drugs. In this work, physicochemical characteristics of 3,6-diHydroxyflavone (3,6-diHF) binding bovine serum albumin (BSA) on PEG (Tween20, L64, and Myrj52)-coated SNPs have been investigated by steady-state and time-resolved fluorescence spectroscopy. These interactions give rise to the formation of intermolecular and intramolecular H bonds. As a subject of interest, the effect of temperature (30-60 °C) on the H bonds was studied by steady-state fluorescence. The size distribution and zeta potential of SNPs were determined by dynamic light scattering (DLS). Scanning electron microscopy (SEM) analysis revealed the spherical nature of particles with average diameter 40-80 nm. The structure, stability, dynamics, and conformational changes in adsorbed BSA protein on the PEG-coated SNPs surface have been also investigated by steady-state/lifetime fluorescence and circular dichroism spectroscopy. The results have relevance in the oxidative stress and drug delivery processes.

Effects of ammonium sulfate and sodium chloride concentration on PEG/protein liquid-liquid phase separation.

PubMed

Dumetz, André C; Lewus, Rachael A; Lenhoff, Abraham M; Kaler, Eric W

2008-09-16

When added to protein solutions, poly(ethylene glycol) (PEG) creates an effective attraction between protein molecules due to depletion forces. This effect has been widely used to crystallize proteins, and PEG is among the most successful crystallization agents in current use. However, PEG is almost always used in combination with a salt at either low or relatively high concentrations. Here the effects of sodium chloride and ammonium sulfate concentration on PEG 8000/ovalbumin liquid-liquid (L-L) phase separation are investigated. At low salt the L-L phase separation occurs at decreasing protein concentration with increasing salt concentration, presumably due to repulsive electrostatic interactions between proteins. At high salt concentration, the behavior depends on the nature of the salt. Sodium chloride has little effect on the L-L phase separation, but ammonium sulfate decreases the protein concentration at which the L-L phase separation occurs. This trend is attributed to the effects of critical fluctuations on depletion forces. The implications of these results for designing solution conditions optimal for protein crystallization are discussed.

Characterization of PEG-Like Macromolecular Coatings on Plasma Modified NiTi Alloy

NASA Astrophysics Data System (ADS)

Yang, Jun; Gao, Jiacheng; Chang, Peng; Wang, Jianhua

2008-04-01

A poly (ethylene glycol) (PEG-like) coating was developed to improve the biocompatibility of Nickel-Titanium (NiTi) alloy implants. The PEG-like macromolecular coatings were deposited on NiTi substrates at a room temperature of 298 K through a ECR (electron-cyclotron resonance) cold-plasma enhanced chemical vapor deposition method using tetraglyme (CH3-O-(CH2-CH2-O)4-CH3) as a precursor. A power supply with a frequency of 2.45 GHz was applied to ignite the plasma with Ar(argon) used as the carrier gas. Based on the atomic force microscopy (AFM) studies, a thin smooth coating on NiTi substrates with highly amorphous functional groups on the modified NiTi surfaces were mainly the same accumulated stoichiometric ratio of C and O with PEG. The vitro studies showed that platelet-rich plasma (PRP) adsorption on the modified NiTi alloy surface was significantly reduced. This study indicated that plasma surface modification changes the surface components of NiTi alloy and subsequently improves its biocompatibility.

Face and Construct Validation of a Virtual Peg Transfer Simulator

PubMed Central

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

2013-01-01

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

Size-controlled synthesis of NiFe2O4 nanospheres via a PEG assisted hydrothermal route and their catalytic properties in oxidation of alcohols by periodic acid

NASA Astrophysics Data System (ADS)

Paul, Bappi; Purkayastha, Debraj Dhar; Dhar, Siddhartha Sankar

2016-05-01

A novel and facile approach for synthesis of spinel nickel ferrites (NiFe2O4) nanoparticles (NPs) employing homogeneous chemical precipitation followed by hydrothermal heating is reported. The synthesis involves use of tributylamine (TBA) as a hydroxylating agent in synthesis of nickel ferrites. Polyethylene glycol (PEG) 4000 was used as surfactant. As-synthesized NiFe2O4 NPs were characterized by powder X-ray diffraction (XRD), transmission electron microscopy (TEM), N2 adsorption-desorption isotherm (BET) and vibrating sample magnetometry (VSM). The XRD pattern revealed formation of cubic face-centered NiFe2O4 and TEM image showed spherical particles of sizes 2-10 nm. These NiFe2O4 NPs were used as magnetically recoverable catalyst in oxidation of cyclic alcohols to their corresponding aldehydes by periodic acid. This eco-friendly procedure affords products in very high yield and selectivity. The reusability of the catalyst is proved to be noteworthy as the material exhibits no significant changes in its catalytic activity even after five cycles of reuse.

PLGA-mPEG nanoparticles of cisplatin: in vitro nanoparticle degradation, in vitro drug release and in vivo drug residence in blood properties.

PubMed

Avgoustakis, K; Beletsi, A; Panagi, Z; Klepetsanis, P; Karydas, A G; Ithakissios, D S

2002-02-19

The in vitro nanoparticle degradation, in vitro drug release and in vivo drug residence in blood properties of PLGA-mPEG nanoparticles of cisplatin were investigated. The nanoparticles were prepared by a double emulsion method and characterized with regard to their morphology, size, zeta potential and drug loading. The rate of in vitro degradation of the PLGA-mPEG nanoparticles in PBS (pH 7.4) depended on their composition, increasing when the mPEG content (mPEG:PLGA ratio) of the nanoparticles increased. Sustained cisplatin release over several hours from the PLGA-mPEG nanoparticles in vitro (PBS) was observed. The composition of the nanoparticles affected drug release: the rate of release increased when the mPEG content of the nanoparticles increased. Within the range of drug loadings investigated, the drug loading of the nanoparticles did not have any significant effect on drug release. The loading efficiency was low and needs improvement in order to obtain PLGA-mPEG nanoparticles with a satisfactory cisplatin content for therapeutic application. The i.v. administration of PLGA-mPEG nanoparticles of cisplatin in BALB/c mice resulted in prolonged cisplatin residence in systemic blood circulation. The results appear to justify further investigation of the suitability of the PLGA-mPEG nanoparticles for the controlled i.v. delivery and/or targeting of cisplatin.

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

PubMed

Cui, Qianling; Wu, Feipeng; Wang, Erjian

2011-05-19

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

Biocatalytic route to sugar-PEG-based polymers for drug delivery applications.

PubMed

Bhatia, Sumati; Mohr, Andreas; Mathur, Divya; Parmar, Virinder S; Haag, Rainer; Prasad, Ashok K

2011-10-10

Sugar-PEG-based polymers were synthesized by enzymatic copolymerization of 4-C-hydroxymethyl-1,2-O-isopropylidene-β-L-threo-pentofuranose/4-C-hydroxymethyl-1,2-O-benzylidene-β-L-threo-pentofuranose/4-C-hydroxymethyl-1,2-O-isopropylidene-3-O-pentyl-β-L-threo-pentofuranose with PEG-600 dimethyl ester using Novozyme-435 (Candida antarctica lipase immobilized on polyacrylate). Carbohydrate monomers were obtained by the multistep synthesis starting from diacetone-D-glucose and PEG-600 dimethyl ester, which was in turn obtained by the esterification of the commercially available PEG-600 diacid. Aggregation studies on the copolymers revealed that in aqueous solution those polymers bearing the hydrophobic pentyl/benzylidene moiety spontaneously self-assembled into supramolecular aggregates. The critical aggregation concentration (CAC) of polymers was determined by surface tension measurements, and the precise size of the aggregates was obtained by dynamic light scattering. The polymeric aggregates were further explored for their drug encapsulation properties in buffered aqueous solution of pH 7.4 (37 °C) using nile red as a hydrophobic model compound by means of UV/vis and fluorescence spectroscopy. There was no significant encapsulation in polymer synthesized from 4-C-hydroxymethyl-1,2-O-isopropylidene-β-L-threo-pentofuranose because this sugar monomer does not contain a big hydrophobic moiety as the pentyl or the benzylidene moiety. Nile red release study was performed at pH 5.0 and 7.4 using fluorescence spectroscopy. The release of nile red from the polymer bearing benzylidene moiety and pentyl moiety was observed with a half life of 3.4 and 2.0 h, respectively at pH 5.0, whereas no release was found at pH 7.4.

Targeted gene delivery by polyplex micelles with crowded PEG palisade and cRGD moiety for systemic treatment of pancreatic tumors.

PubMed

Ge, Zhishen; Chen, Qixian; Osada, Kensuke; Liu, Xueying; Tockary, Theofilus A; Uchida, Satoshi; Dirisala, Anjaneyulu; Ishii, Takehiko; Nomoto, Takahiro; Toh, Kazuko; Matsumoto, Yu; Oba, Makoto; Kano, Mitsunobu R; Itaka, Keiji; Kataoka, Kazunori

2014-03-01

Adequate retention in systemic circulation is the preliminary requirement for systemic gene delivery to afford high bioavailability into the targeted site. Polyplex micelle formulated through self-assembly of oppositely-charged poly(ethylene glycol) (PEG)-polycation block copolymer and plasmid DNA has gained tempting perspective upon its advantageous core-shell architecture, where outer hydrophilic PEG shell offers superior stealth behaviors. Aiming to promote these potential characters toward systemic applications, we strategically introduced hydrophobic cholesteryl moiety at the ω-terminus of block copolymer, anticipating to promote not only the stability of polyplex structure but also the tethered PEG crowdedness. Moreover, Mw of PEG in the PEGylated polyplex micelle was elongated up to 20 kDa for expecting further enhancement in PEG crowdedness. Furthermore, cyclic RGD peptide as ligand molecule to integrin receptors was installed at the distal end of PEG in order for facilitating targeted delivery to the tumor site as well as promoting cellular uptake and intracellular trafficking behaviors. Thus constructed cRGD conjugated polyplex micelle with the elevated PEG shielding was challenged to a modeled intractable pancreatic cancer in mice, achieving potent tumor growth suppression by efficient gene expression of antiangiogenic protein (sFlt-1) at the tumor site. Copyright © 2013 Elsevier Ltd. All rights reserved.

Prevention of Oxidized Low Density Lipoprotein-Induced Endothelial Cell Injury by DA-PLGA-PEG-cRGD Nanoparticles Combined with Ultrasound

PubMed Central

Li, Zhaojun; Huang, Hui; Huang, Lili; Du, Lianfang; Sun, Ying; Duan, Yourong

2017-01-01

In general, atherosclerosis is considered to be a form of chronic inflammation. Dexamethasone has anti-inflammatory effects in atherosclerosis, but it was not considered for long-term administration on account of a poor pharmacokinetic profile and adverse side effects. Nanoparticles in which drugs can be dissolved, encapsulated, entrapped or chemically attached to the particle surface have abilities to incorporate dexamethasone and to be used as controlled or targeted drug delivery system. Long circulatory polymeric nanoparticles present as an assisting approach for controlled and targeted release of the encapsulated drug at the atherosclerotic site. Polymeric nanoparticles combined with ultrasound (US) are widely applied in cancer treatment due to their time applications, low cost, simplicity, and safety. However, there are few studies on atherosclerosis treatment using polymeric nanoparticles combined with US. In this study, targeted dexamethasone acetate (DA)-loaded poly (lactide-glycolide)-polyethylene glycol-cRGD (PLGA-PEG-cRGD) nanoparticles (DA-PLGA-PEG-cRGD NPs) were prepared by the emulsion-evaporation method using cRGD modified PLGA-PEG polymeric materials (PLGA-PEG-cRGD) prepared as the carrier. The average particle size of DA-PLGA-PEG-cRGD NPs was 221.6 ± 0.9 nm. Morphology of the nanoparticles was spherical and uniformly dispersed. In addition, the DA released profiles suggested that ultrasound could promote drug release from the nanocarriers and accelerate the rate of release. In vitro, the cellular uptake process of fluorescein isothiocyanate (FITC)@DA-PLGA-PEG-cRGD NPs combined with US into the damaged human umbilical vein endothelial cells (HUVECs) indicated that US promoted rapid intracellular uptake of FITC@DA- PLGA-PEG-cRGD NPs. The cell viability of DA-PLGA-PEG-cRGD NPs combined with US reached 91.9% ± 0.2%, which demonstrated that DA-PLGA-PEG-cRGD NPs combined with US had a positive therapeutic effect on damaged HUVECs. Overall, DA-PLGA-PEG

Prevention of Oxidized Low Density Lipoprotein-Induced Endothelial Cell Injury by DA-PLGA-PEG-cRGD Nanoparticles Combined with Ultrasound.

PubMed

Li, Zhaojun; Huang, Hui; Huang, Lili; Du, Lianfang; Sun, Ying; Duan, Yourong

2017-04-13

In general, atherosclerosis is considered to be a form of chronic inflammation. Dexamethasone has anti-inflammatory effects in atherosclerosis, but it was not considered for long-term administration on account of a poor pharmacokinetic profile and adverse side effects. Nanoparticles in which drugs can be dissolved, encapsulated, entrapped or chemically attached to the particle surface have abilities to incorporate dexamethasone and to be used as controlled or targeted drug delivery system. Long circulatory polymeric nanoparticles present as an assisting approach for controlled and targeted release of the encapsulated drug at the atherosclerotic site. Polymeric nanoparticles combined with ultrasound (US) are widely applied in cancer treatment due to their time applications, low cost, simplicity, and safety. However, there are few studies on atherosclerosis treatment using polymeric nanoparticles combined with US. In this study, targeted dexamethasone acetate (DA)-loaded poly (lactide-glycolide)-polyethylene glycol-cRGD (PLGA-PEG-cRGD) nanoparticles (DA-PLGA-PEG-cRGD NPs) were prepared by the emulsion-evaporation method using cRGD modified PLGA-PEG polymeric materials (PLGA-PEG-cRGD) prepared as the carrier. The average particle size of DA-PLGA-PEG-cRGD NPs was 221.6 ± 0.9 nm. Morphology of the nanoparticles was spherical and uniformly dispersed. In addition, the DA released profiles suggested that ultrasound could promote drug release from the nanocarriers and accelerate the rate of release. In vitro, the cellular uptake process of fluorescein isothiocyanate (FITC)@DA-PLGA-PEG-cRGD NPs combined with US into the damaged human umbilical vein endothelial cells (HUVECs) indicated that US promoted rapid intracellular uptake of FITC@DA- PLGA-PEG-cRGD NPs. The cell viability of DA-PLGA-PEG-cRGD NPs combined with US reached 91.9% ± 0.2%, which demonstrated that DA-PLGA-PEG-cRGD NPs combined with US had a positive therapeutic effect on damaged HUVECs. Overall, DA-PLGA-PEG

Structure and Dynamics of Highly PEG-ylated Sterically Stabilized Micelles in Aqueous Media

PubMed Central

Vuković, Lela; Khatib, Fatima A.; Drake, Stephanie P.; Madriaga, Antonett; Brandenburg, Kenneth S.; Král, Petr; Onyuksel, Hayat

2011-01-01

Molecular assemblies of highly PEG-ylated phospholipids are important in many biomedical applications. We study sterically stabilized micelles (SSM) of self-assembled DSPE-PEG2000 in pure water and isotonic HEPES buffered saline solution. The observed SSM sizes of 2 – 15 nm largely depend on the solvent and the lipid concentration used. The critical micelle concentration (CMC) of DSPE-PEG2000 is ≈ 10 times higher in water than in buffer and the viscosity of the dispersion dramatically increases with the lipid concentration. To explain the experimentally observed results, we perform atomistic molecular dynamics simulations of the solvated SSM. Our modeling reveal that the observed assemblies have very different aggregation numbers of Nagg ≈ 90 (saline solution) and Nagg < 8 (water), due to very different screening of their charged −PO4− groups. We also demonstrate that the micelle cores can inflate and their corona highly fluctuate, allowing thus storage and delivery of molecules with different chemistry. PMID:21780810

Structure and dynamics of highly PEG-ylated sterically stabilized micelles in aqueous media.

PubMed

Vuković, Lela; Khatib, Fatima A; Drake, Stephanie P; Madriaga, Antonett; Brandenburg, Kenneth S; Král, Petr; Onyuksel, Hayat

2011-08-31

Molecular assemblies of highly PEG-ylated phospholipids are important in many biomedical applications. We have studied sterically stabilized micelles (SSMs) of self-assembled DSPE–PEG2000 in pure water and isotonic HEPES-buffered saline solution. The observed SSM sizes of 2–15 nm largely depend on the solvent and the lipid concentration used. The critical micelle concentration of DSPE–PEG2000 is 10 times higher in water than in buffer, and the viscosity of the dispersion dramatically increases with the lipid concentration. To explain the experimentally observed results, we performed atomistic molecular dynamics simulations of solvated SSMs. Our modeling revealed that the observed assemblies have very different aggregation numbers (N(agg) ≈ 90 in saline solution and N(agg) < 8 in water) because of very different screening of their charged PO4(–) groups. We also demonstrate that the micelle cores can inflate and their coronas can fluctuate strongly, thus allowing storage and delivery of molecules with different chemistries.

Effects of Terminal Sterilization on PEG-Based Bioresorbable Polymers Used in Biomedical Applications.

PubMed

Bhatnagar, Divya; Dube, Koustubh; Damodaran, Vinod B; Subramanian, Ganesan; Aston, Kenneth; Halperin, Frederick; Mao, Meiyu; Pricer, Kurt; Murthy, N Sanjeeva; Kohn, Joachim

2016-10-01

The effects of ethylene oxide (EO), vaporized hydrogen peroxide (VHP), gamma (γ) radiation, and electron-beam (E-beam) on the physiochemical and morphological properties of medical device polymers are investigated. Polymers with ether, carbonate, carboxylic acid, amide and ester functionalities are selected from a family of poly(ethylene glycol) (PEG) containing tyrosine-derived polycarbonates (TyrPCs) to include slow, medium, fast, and ultrafast degrading polymers. Poly(lactic acid) (PLA) is used for comparison. Molecular weight ( M w ) of all tested polymers decreases upon gamma and E-beam, and this effect becomes more pronounced at higher PEG content. Gamma sterilization increases the glass transition temperature of polymers with high PEG content. EO esterifies the carboxylic acid groups in desaminotyrosol-tyrosine (DT) and causes significant degradation. VHP causes hydroxylation of the phenyl ring, and hydrolytic degradation. This study signifies the importance of the chemical composition when selecting a sterilization method, and provides suggested conditions for each of the sterilization methods.

Effects of PEG tethering chain length of vitamin E TPGS with a Herceptin-functionalized nanoparticle formulation for targeted delivery of anticancer drugs.

PubMed

Zhao, Jing; Feng, Si-Shen

2014-03-01

Drug formulation by ligand conjugated nanoparticles of biodegradable polymers has become one of the most important strategies in drug targeting. We have developed in our previous work nanoparticles of a mixture of two vitamin E TPGS based copolymers PLA-TPGS and TPGS-TOOH with the latter for Herceptin conjugation for targeted delivery of anticancer drugs such as docetaxel to the cancer cells of human epidermal growth factor receptor 2 (HER2) overexpression. In this research, we investigated the effects of the PEG chain length in TPGS, which is in fact a PEGylated vitamin E, on the cellular uptake and cytotoxicity of the drug formulated in the Herceptin-conjugated nanoparticles of PLA-TPGS/TPGS-COOH blend (NPs). Such NPs of PEG1000, PEG2000, PEG3350 and PEG5000, i.e. the PEG of molecule weight 1000, 2000, 3350 and 5000, were prepared by the nanoprecipitation method and characterized for their size and size distribution, drug loading, surface morphology, surface charge and surface chemistry as well as in vitro drug release profile, cellular uptake and cytotoxicity. We found among such nanoparticles, those of PEG1000, i.e. of the shortest PEG tethering chain length, could result in the best therapeutic effects, which are 24.1%, 37.3%, 38.1% more efficient in cellular uptake and 68.1%, 90%, 92.6% lower in IC50 (thus higher in cytotoxicity) than the Herceptin-conjugated nanoparticles of PLA-TPGS/TPGS-COOH blend of PEG2000, PEG3350 and PEG5000 respectively in treatment of SK-BR-3 cancer cells which are of high HER2 overexpression. We provided a theoretical explanation from surface mechanics and thermodynamics for endocytosis of nanoparticles. Copyright © 2014 Elsevier Ltd. All rights reserved.

PEG-lipid-PLGA hybrid nanoparticles loaded with berberine-phospholipid complex to facilitate the oral delivery efficiency.

PubMed

Yu, Fei; Ao, Mingtao; Zheng, Xiao; Li, Nini; Xia, Junjie; Li, Yang; Li, Donghui; Hou, Zhenqing; Qi, Zhongquan; Chen, Xiao Dong

2017-11-01

The natural product berberine (BBR), present in various plants, arouses great interests because of its numerous pharmacological effects. However, the further development and application of BBR had been hampered by its poor oral bioavailability. In this work, we report on polymer-lipid hybrid nanoparticles (PEG-lipid-PLGA NPs) loaded with BBR phospholipid complex using a solvent evaporation method for enhancing the oral BBR efficiency. The advantage of this new drug delivery system is that the BBR-soybean phosphatidylcholine complex (BBR-SPC) could be used to enhance the liposolubility of BBR and improve the affinity with the biodegradable polymer to increase the drug-loading capacity and controlled/sustained release. The entrapment efficiency of the PEG-lipid-PLGA NPs/BBR-SPC was observed to approach approximately 89% which is more than 2.4 times compared with that of the PEG-lipid-PLGA NPs/BBR. To the best of our knowledge, this is the first report on using polymer material for effective encapsulation of BBR to improve its oral bioavailability. The prepared BBR delivery systems demonstrated a uniform spherical shape, a well-dispersed core-shell structure and a small particle size (149.6 ± 5.1 nm). The crystallographic and thermal analysis has indicated that the BBR dispersed in the PEG-lipid-PLGA NPs matrix is in an amorphous form. More importantly, the enhancement in the oral relative bioavailability of the PEG-lipid-PLGA NPs/BBR-SPC was ∼343% compared with that of BBR. These positive results demonstrated that PEG-lipid-PLGA NPs/BBR-SPC may have the potential for facilitating the oral drug delivery of BBR.

A computational study suggests that replacing PEG with PMOZ may increase exposure of hydrophobic targeting moiety.

PubMed

Magarkar, Aniket; Róg, Tomasz; Bunker, Alex

2017-05-30

In a previous study we showed that the cause of failure of a new, proposed, targeting ligand, the AETP moiety, when attached to a PEGylated liposome, was occlusion by the poly(ethylene glycol) (PEG) layer due to its hydrophobic nature, given that PEG is not entirely hydrophilic. At the time we proposed that possible replacement with a more hydrophilic protective polymer could alleviate this problem. In this study we have used computational molecular dynamics modelling, using a model with all atom resolution, to suggest that a specific alternative protective polymer, poly(2-methyloxazoline) (PMOZ), would perform exactly this function. Our results show that when PEG is replaced by PMOZ the relative exposure to the solvent of AETP is increased to a level even greater than that we found in previous simulations for the RGD peptide, a targeting moiety that has previously been used successfully in PEGylated liposome based therapies. While the AETP moiety itself is no longer under consideration, the results of this computational study have broader significance: the use of PMOZ as an alternative polymer coating to PEG could be efficacious in the context of more hydrophobic targeting ligands. In addition to PMOZ we studied another polyoxazoline, poly(2-ethyloxazoline) (PEOZ), that has also been mooted as a possible alternate protective polymer. It was also found that the RDG peptide occlusion was significantly greater for the case of both oxazolines as opposed to PEG and that, unlike PEG, neither oxazoline entered the membrane. As far as we are aware this is the first time that polyoxazolines have been studied using molecular dynamics simulation with all atom resolution. Copyright © 2017 Elsevier B.V. All rights reserved.

Nanosilica sol leads to further increase in polyethylene glycol (PEG) 1000-enhanced thermostability of β-cyclodextrin glycosyltransferase from Bacillus circulans.

PubMed

Li, Caiming; Huang, Min; Gu, Zhengbiao; Hong, Yan; Cheng, Li; Li, Zhaofeng

2014-04-02

A major disadvantage of cyclodextrin production is the limited thermostability of cyclodextrin glycosyltransferase. The ability of combinations of nanosilica sol with polyethylene glycol (PEG) 1000 to enhance the thermostability of the β-cyclodextrin glycosyltransferase from Bacillus circulans was investigated. It was found that 10% PEG 1000 combined with 0.05% nanosilica sol could activate the β-cyclodextrin glycosyltransferase by 17.2%. Furthermore, 0.05% nanosilica sol leads to further increase in PEG 1000-enhanced thermostability of β-cyclodextrin glycosyltransferase. With the simultaneous addition of 10% PEG 1000 and 0.05% nanosilica into the enzyme solution, which was allowed to incubate for 60 min at 60 °C, 61.3% of β-cyclodextrin-forming activity could be retained, which was much higher than that with only 10% PEG 1000 added. Atomic force microscopy, fluorescence spectroscopy, and circular dichroism analysis indicated that silica nanoparticles helped PEG 1000 further protect the tertiary and secondary structures of β-cyclodextrin glycosyltransferase. This study provides an effective approach for improving the thermostability of cyclodextrin glycosyltransferase and related enzymes.

Effect of molecular weight and ratio of poly ethylene glycols' derivatives in combination with trehalose on stability of freeze-dried IgG.

PubMed

Mohammad Zadeh, Amir Hossein; Rouholamini Najafabadi, Abdolhosein; Vatanara, Alireza; Faghihi, Homa; Gilani, Kambiz

2017-12-01

The influence of poly ethylene glycol (PEG) at different molecular weights (MWs) and ratios was studied on the stability of freeze-dried immune globulin G (IgG). PEGs (600-4000 Dalton) at concentrations of 0.5 and 5% W/V were applied in the presence of 40 and 60% W/W of trehalose to prepare freeze-dried IgG formulations. Size-exclusion chromatography, infra-red spectroscopy, differential scanning calorimeter, and gel electrophoresis were performed to characterize lyophilized samples. Pure IgG demonstrated the highest aggregation of 5.77 ± 0.10% after process and 12.66 ± 0.50% as well as 44.69 ± 0.50% upon 1 and 2 months of storage at 45 °C, respectively. 5% W/V of PEGs 4000 in combination with 40% W/W trehalose, significantly suppressed aggregation, 0.05 ± 0.01%, with minimum aggregation rate constant of 0.32 (1/month). The integrity of IgG molecules and secondary conformation were properly preserved in all formulations comparing native IgG. It could be concluded that appropriate concentration and MW of PEGs, prominently augmented stabilizing effect of trehalose on freeze-dried antibody through inserting additional supportive mechanisms of actions.

Purification of inclusion bodies using PEG precipitation under denaturing conditions to produce recombinant therapeutic proteins from Escherichia coli.

PubMed

Chen, Huanhuan; Li, Ninghuan; Xie, Yueqing; Jiang, Hua; Yang, Xiaoyi; Cagliero, Cedric; Shi, Siwei; Zhu, Chencen; Luo, Han; Chen, Junsheng; Zhang, Lei; Zhao, Menglin; Feng, Lei; Lu, Huili; Zhu, Jianwei

2017-07-01

It has been documented that the purification of inclusion bodies from Escherichia coli by size exclusion chromatography (SEC) may benefit subsequent refolding and recovery of recombinant proteins. However, loading volume and the high cost of the column limits its application in large-scale manufacturing of biopharmaceutical proteins. We report a novel process using polyethylene glycol (PEG) precipitation under denaturing conditions to replace SEC for rapid purification of inclusion bodies containing recombinant therapeutic proteins. Using recombinant human interleukin 15 (rhIL-15) as an example, inclusion bodies of rhIL-15 were solubilized in 7 M guanidine hydrochloride, and rhIL-15 was precipitated by the addition of PEG 6000. A final concentration of 5% (w/v) PEG 6000 was found to be optimal to precipitate target proteins and enhance recovery and purity. Compared to the previously reported S-200 size exclusion purification method, PEG precipitation was easier to scale up and achieved the same protein yields and quality of the product. PEG precipitation also reduced manufacturing time by about 50 and 95% of material costs. After refolding and further purification, the rhIL-15 product was highly pure and demonstrated a comparable bioactivity with a rhIL-15 reference standard. Our studies demonstrated that PEG precipitation of inclusion bodies under denaturing conditions holds significant potential as a manufacturing process for biopharmaceuticals from E. coli protein expression systems.

Effect of PEG6000 on the in vitro and in vivo transdermal permeation of ondansetron hydrochloride from EVA1802 membranes.

PubMed

Krishnaiah, Yellela S R; Rama, Bukka; Raghumurthy, Vanambattina; Ramanamurthy, Kolapalli V; Satyanarayana, Vemulapalli

2009-01-01

The objective was to evaluate ethylene vinyl acetate (EVA) copolymer membranes with vinyl acetate content of 18% w/w (EVA1802) for transdermal delivery of ondansetron hydrochloride. The EVA1802 membranes containing selected concentrations (0, 5, 10 and 15% w/w) of PEG6000 were prepared, and subjected to in vitro permeation studies from a nerodilol-based drug reservoir. Flux of ondansetron from EVA1802 membranes without PEG6000 was 64.1 +/- 0.6 microg/cm(2.)h, and with 10%w/w of PEG6000 (EVA1802-PEG6000-10) it increased to 194.9 +/- 4.6 microg/cm(2.)h. However, with 15%w/w of PEG6000, EVA1802 membranes produced a burst release of drug which in turn decreased drug flux. The EVA1802-PEG6000-10 membrane was coated with an adhesive emulsion, applied to rat epidermis and subjected to in vitro permeation studies against controls. Flux of ondansetron from transdermal patch across rat epidermis was 111.7 +/- 1.3 microg/cm(2.)h, which is about 1.3 times the required flux. A TTS was fabricated using adhesive-coated EVA1802-PEG6000-10 membrane and other TTS components, and subjected to in vivo delivery in human volunteers against a control. It was concluded from the comparative pharmacokinetic study that TTS of ondansetron, prepared with EVA1802-PEG6000-10 membrane, provided average steady-state plasma concentration on par with multiple-dosed oral tablets, but with a low percent of peak-to-trough fluctuation.

Development, optimization, and in vitro characterization of dasatinib-loaded PEG functionalized chitosan capped gold nanoparticles using Box-Behnken experimental design.

PubMed

Adena, Sandeep Kumar Reddy; Upadhyay, Mansi; Vardhan, Harsh; Mishra, Brahmeshwar

2018-03-01

The purpose of this research study was to develop, optimize, and characterize dasatinib loaded polyethylene glycol (PEG) stabilized chitosan capped gold nanoparticles (DSB-PEG-Ch-GNPs). Gold (III) chloride hydrate was reduced with chitosan and the resulting nanoparticles were coated with thiol-terminated PEG and loaded with dasatinib (DSB). Plackett-Burman design (PBD) followed by Box-Behnken experimental design (BBD) were employed to optimize the process parameters. Polynomial equations, contour, and 3D response surface plots were generated to relate the factors and responses. The optimized DSB-PEG-Ch-GNPs were characterized by FTIR, XRD, HR-SEM, EDX, TEM, SAED, AFM, DLS, and ZP. The results of the optimized DSB-PEG-Ch-GNPs showed particle size (PS) of 24.39 ± 1.82 nm, apparent drug content (ADC) of 72.06 ± 0.86%, and zeta potential (ZP) of -13.91 ± 1.21 mV. The responses observed and the predicted values of the optimized process were found to be close. The shape and surface morphology studies showed that the resulting DSB-PEG-Ch-GNPs were spherical and smooth. The stability and in vitro drug release studies confirmed that the optimized formulation was stable at different conditions of storage and exhibited a sustained drug release of the drug of up to 76% in 48 h and followed Korsmeyer-Peppas release kinetic model. A process for preparing gold nanoparticles using chitosan, anchoring PEG to the particle surface, and entrapping dasatinib in the chitosan-PEG surface corona was optimized.

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

PubMed

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

2007-10-01

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

The scheme of a blindless positioning structure with parallel adjusting tables and swing rods for 4000 optical fibres of LAMOST.

NASA Astrophysics Data System (ADS)

Yunguo, Gao

1996-12-01

This scheme structure is for positioning 4000 optical fibres of LAMOST telescope. It adopts the swing rods adjusted parallel and simultaneously by many small tables. The problems, for example, positioning accuracy of the optical fibers, the time to readjust all the 4000 optical fibres and error correction, etc. have been considered in the scheme. The structure has no blind area.

Establishment of the first international standard for PEGylated granulocyte colony stimulating factor (PEG-G-CSF): Report of an international collaborative study

PubMed Central

Wadhwa, Meenu; Bird, Chris; Dougall, Thomas; Rigsby, Peter; Bristow, Adrian; Thorpe, Robin

2015-01-01

We assessed the feasibility of developing a suitable international reference standard for determination of in vitro biological activity of human sequence recombinant PEG-G-CSF products with a 20 kD linear PEG linked to the N-terminal methionyl residue of G-CSF (INN Filgrastim), produced using a conjugation process and coupling chemistry similar to that employed for the lead PEGfilgrastim product. Based on initial data which showed that the current WHO 2nd international standard, IS for G-CSF (09/136) or alternatively, a PEG-G-CSF standard with a unitage traceable to the G-CSF IS may potentially serve as the IS for PEG-G-CSF products, two candidate preparations of PEG-G-CSF were formulated and lyophilized at NIBSC. These preparations were tested by 23 laboratories using in vitro bioassays in a multi-centre collaborative study. Results indicated that on the basis of parallelism, the current WHO 2nd IS for G-CSF or any of the PEG-G-CSF samples could be used as the international standard for PEG-G-CSF preparations. However, because of the variability in potency estimates seen when PEG-G-CSF preparations were compared with the current WHO 2nd IS for G-CSF, a candidate PEG-G-CSF was suitable as the WHO IS. The preparation 12/188 was judged suitable to serve as the WHO IS based on in vitro biological activity data. Therefore, the preparation coded 12/188 was established by the WHO Expert Committee on Biological Standardization (ECBS) in 2013 as the WHO 1st IS for human PEGylated G-CSF with an assigned in vitro bioactivity of 10,000 IU per ampoule. PMID:25450254

The effect of a microgravity (space) environment on the expression of expansins from the peg and root tissues of Cucumis sativus

NASA Technical Reports Server (NTRS)

Link, B. M.; Wagner, E. R.; Cosgrove, D. J.

2001-01-01

In young cucumber seedlings, the peg is a polar outgrowth of tissue that functions by snagging the seed coat, thereby freeing the cotyledons. The development of the peg is thought to be gravity-dependent and has become a model system for plant-gravity response. Peg development requires rapid cell expansion, a process thought to be catalyzed by alpha-expansins, and thus was a good system to identify expansins that were regulated by gravity. This study identified 7 new alpha-expansin cDNAs from cucumber seedlings (Cucumis sativus L. cv Burpee Hybrid II) and examined their expression patterns. Two alpha-expansins (CsExp3 and CsExp4) were more highly expressed in the peg and the root. Earlier reports stated that pegs tend not to form in the absence of gravity, so the expression levels were compared in the pegs of seedlings grown in space (STS-95), on a clinostat, and on earth (1 g). Pegs were observed to form at high frequency on clinostat and space-grown seedlings, yet on clinostats there was more than a 4-fold reduction in the expression of CsExp3 in the pegs of seedlings grown on clinostats vs. those grown at 1 g, while the CsExp4 gene appeared to be turned off (below detection limits). There were no detectable differences in expansin gene expression levels for the pegs of seedlings grown in space or in the orbiter environmental simulator (OES) (1 g) at NASA. The microgravity environment did not affect the expression of CsExp3 or CsExp4, and the clinostat did not simulate the microgravity environment well.

Tolerability, safety, and efficacy of PEG 3350 as a 1-day bowel preparation in children.

PubMed

Walia, Ritu; Steffen, Rita; Feinberg, Lisa; Worley, Sarah; Mahajan, Lori

2013-02-01

The aim of the study was to evaluate the tolerability, safety, and efficacy of polyethylene glycol (PEG) 3350 without electrolytes as a 1-day bowel preparation for colonoscopy in children. A prospective study of 45 children undergoing colonoscopy prescribed PEG 3350 without electrolytes mixed with a commercial electrolyte beverage was performed. Patients <45 kg received 136 g of PEG 3350 without electrolytes mixed in 32 ounces of Gatorade. Patients ≥ 45 kg were given 255 g of PEG 3350 without electrolytes in 64 ounces of Gatorade A basic metabolic panel was performed at the time of the clinic visit and just before colonoscopy. Patients completed a survey related to bowel preparation. Endoscopists graded bowel preparation and noted the proximal extent of the examination. A total of 44 patients (14 ± 3 years) completed the study. One patient was excluded due to protocol breach. All subjects reported the preparation was easy (61%) or tolerable (39%). Adverse events included nausea (34%), abdominal pain (23%), vomiting (16%), abdominal distension (20%), bloating (23%), and dizziness (7%). Although significant changes in serum glucose and CO2 were noted, no therapeutic interventions were indicated. Significant changes in sodium, potassium chloride, blood urea nitrogen, or creatinine did not occur. Colonic preparation was rated as excellent in 23%, good in 52%, fair in 23%, and poor in 2% of patients. Intubation of the ileum was successful in 100%. One-day bowel preparation with high dose PEG 3350 mixed with commercial electrolyte solution is tolerable, safe, and effective in children before colonoscopy.

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

PubMed

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

2004-06-01

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

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

PubMed

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

2018-05-01

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

Functionalization of Cellulose Nanocrystals with PEG-Metal-Chelating Diblock Copolymers via Controlled Conjugation in Aqueous Medium

NASA Astrophysics Data System (ADS)

Guo, Melinda

The surface of cellulose nanocrystals (CNCs) was successfully functionalized with metal chelating diblock copolymers via HyNic-4FB conjugation. Two types of PEG-metal-chelating block polymers with hydrazinonicotinate acetone hydrazine (HyNic) end groups were synthesized: mPEG-PGlu(DTPA) 18-HyNic and mPEG-PGlu(DTPA)25-HyNic. These two polymers both had a methoxy PEG (M ˜ 2000 Da) block that differed in the mean degree of polymerization of the metal-chelating block. They were characterized by 1H NMR spectroscopy and gel-permeation chromatography (GPC). 4-Formylbenzamide (4FB) groups were introduced onto the surface of CNCs and quantified through their reaction with 2-hydrazinopyridine. The polymers were grafted onto the surface of CNCs via bis-aryl hydrazone bond formation, and the kinetics of this reaction was explored by UV/Vis spectroscopy. The CNCs were also labeled with rhodamine and Alexa FluorRTM 488 dyes. Students in our collaborator's group in Pharmacy are examining applications of these materials as radiotherapeutic agents for cancer treatment.

Efficient Self-Assembly of mPEG End-Capped Porous Silica as a Redox-Sensitive Nanocarrier for Controlled Doxorubicin Delivery.

PubMed

Nguyen, Anh Khoa; Nguyen, Thi Hiep; Bao, Bui Quoc; Bach, Long Giang; Nguyen, Dai Hai

2018-01-01

Porous nanosilica (PNS) has been regarded as a promising candidate for controlled delivery of anticancer drugs. Unmodified PNS-based nanocarriers, however, showed a burst release of encapsulated drugs, which may limit their clinical uses. In this report, PNS was surface conjugated with adamantylamine (ADA) via disulfide bridges (-SS-), PNS-SS-ADA, which was further modified with cyclodextrin-poly(ethylene glycol) methyl ether conjugate (CD-mPEG) to form a core@shell structure PNS-SS-ADA@CD-mPEG for redox triggered delivery of doxorubicin (DOX), DOX/PNS-SS-ADA@CD-mPEG. The prepared PNS-SS-ADA@CD-mPEG nanoparticles were spherical in shape with an average diameter of 55.5 ± 3.05 nm, a little larger than their parentally PNS nanocarriers, at 49.6 ± 2.56 nm. In addition, these nanoparticles possessed high drug loading capacity, at 79.2 ± 3.2%, for controlled release. The release of DOX from DOX/PNS-SS-ADA@CD-mPEG nanoparticles was controlled and prolonged up to 120 h in PBS medium (pH 7.4), compared to less than 40 h under reducing condition of 5 mM DTT. Notably, the PNS-SS-ADA@CD-mPEG was a biocompatible nanocarrier, and the toxicity of DOX was dramatically reduced after loading drugs into the porous core. This redox-sensitive PNS-SS-ADA@CD-mPEG nanoparticle could be considered a potential candidate with high drug loading capacity and a lower risk of systemic toxicity.

75 FR 55459 - Airworthiness Directives; Pratt & Whitney (PW) PW4000 Series Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-13

... Airworthiness Directives; Pratt & Whitney (PW) PW4000 Series Turbofan Engines AGENCY: Federal Aviation..., PW4152, PW4156A, PW4158, PW4164, PW4168, PW4168A, PW4460, and PW4462 turbofan engines. This AD requires... series turbofan engines. We published the proposed AD in the Federal Register on March 25, 2010 (75 FR...

Simultaneous CCD Photometry of Two Eclipsing Binary Stars in Pegasus - Part2: BX Peg

NASA Astrophysics Data System (ADS)

Alton, K. B.

2013-05-01

BX Peg is an overcontact W UMa binary system (P = 0.280416 d) which has been rather well studied, but not fully understood due to complex changes in eclipse timings and light curve variations attributed to star spots. Photometric data collected in three bandpasses (B, V, and Ic) produced nineteen new times of minimum for BX Peg. These were used to update the linear ephemeris and further analyze potential changes in orbital periodicity by examining long-term changes in eclipse timings. In addition, synthetic fitting of light curves by Roche modeling was accomplished with the assistance of three different programs, two of which employ the Wilson-Devinney code. Different spotted solutions were necessary to achieve the best Roche model fits for BX Peg light curves collected in 2008 and 2011. Overall, the long-;term decrease (9.66 × 10-3 sec y-1) in orbital period defined by the parabolic fit of eclipse timing data could arise from mass transfer or angular momentum loss. The remaining residuals from observed minus predicted eclipse timings for BX Peg exhibit complex but non-random behavior. These may be related to magnetic activity cycles and/or the presence of an unseen mass influencing the times of minimum, however, additional minima need to be collected over a much longer timescale to resolve the nature of these complex changes.

Biomechanical Evaluation of All-Polyethylene Pegged Bony Ingrowth Glenoid Fixation Techniques on Implant Micromotion.

PubMed

Wiater, Brett P; Moravek, James E; Kurdziel, Michael D; Baker, Kevin C; Wiater, J Michael

2016-01-01

Newer glenoid components that allow for hybrid cement fixation via traditional cementation of peripheral pegs and bony ingrowth into an interference-fit central peg introduce the possibility of long-term biological fixation. However, little biomechanical work has been done on the initial stability of these components and the various fixation options. We conducted a study in which all-polyethylene glenoid components with a centrally fluted peg were implanted in polyurethane blocks with interference-fit, hybrid cement, and fully cemented fixation (5 per fixation group). Biomechanical evaluation of glenoid loosening, according to ASTM Standard F-2028-12, subjected the glenoids to 50,000 cycles of rim loading, and glenoid component motion was recorded with 2 differential variable reluctance transducers fixed to each glenoid prosthesis. Fully cemented fixation exhibited significantly less mean distraction in comparison with interference-fit fixation (P < .001) and hybrid cement fixation (P < .001). Hybrid cement fixation exhibited significantly less distraction (P < .001), more compression (P < .001), and no significant difference in glenoid translation (P = .793) in comparison with interference-fit fixation. Fully cemented fixation exhibited the most resistance to glenoid motion in comparison with hybrid cement fixation and interference-fit fixation. However, hybrid cement fixation and interference-fit fixation exhibited equivocal motion. Given these results, cementation of peripheral pegs may confer no additional initial stability over that provided by uncemented interference-fit fixation.

Enhanced thermal properties of novel shape-stabilized PEG composite phase change materials with radial mesoporous silica sphere for thermal energy storage.

PubMed

Min, Xin; Fang, Minghao; Huang, Zhaohui; Liu, Yan'gai; Huang, Yaoting; Wen, Ruilong; Qian, Tingting; Wu, Xiaowen

2015-08-11

Radial mesoporous silica (RMS) sphere was tailor-made for further applications in producing shape-stabilized composite phase change materials (ss-CPCMs) through a facile self-assembly process using CTAB as the main template and TEOS as SiO2 precursor. Novel ss-CPCMs composed of polyethylene glycol (PEG) and RMS were prepared through vacuum impregnating method. Various techniques were employed to characterize the structural and thermal properties of the ss-CPCMs. The DSC results indicated that the PEG/RMS ss-CPCM was a promising candidate for building thermal energy storage applications due to its large latent heat, suitable phase change temperature, good thermal reliability, as well as the excellent chemical compatibility and thermal stability. Importantly, the possible formation mechanisms of both RMS sphere and PEG/RMS composite have also been proposed. The results also indicated that the properties of the PEG/RMS ss-CPCMs are influenced by the adsorption limitation of the PEG molecule from RMS sphere with mesoporous structure and the effect of RMS, as the impurities, on the perfect crystallization of PEG.

Enhanced thermal properties of novel shape-stabilized PEG composite phase change materials with radial mesoporous silica sphere for thermal energy storage

PubMed Central

Min, Xin; Fang, Minghao; Huang, Zhaohui; Liu, Yan’gai; Huang, Yaoting; Wen, Ruilong; Qian, Tingting; Wu, Xiaowen

2015-01-01

Radial mesoporous silica (RMS) sphere was tailor-made for further applications in producing shape-stabilized composite phase change materials (ss-CPCMs) through a facile self-assembly process using CTAB as the main template and TEOS as SiO2 precursor. Novel ss-CPCMs composed of polyethylene glycol (PEG) and RMS were prepared through vacuum impregnating method. Various techniques were employed to characterize the structural and thermal properties of the ss-CPCMs. The DSC results indicated that the PEG/RMS ss-CPCM was a promising candidate for building thermal energy storage applications due to its large latent heat, suitable phase change temperature, good thermal reliability, as well as the excellent chemical compatibility and thermal stability. Importantly, the possible formation mechanisms of both RMS sphere and PEG/RMS composite have also been proposed. The results also indicated that the properties of the PEG/RMS ss-CPCMs are influenced by the adsorption limitation of the PEG molecule from RMS sphere with mesoporous structure and the effect of RMS, as the impurities, on the perfect crystallization of PEG. PMID:26261089

Dendrothele griseocana (Corticiaceae) and related taxa with hyphal pegs

Treesearch

Karen K. Nakasone

2006-01-01

Four Dendrothele (Corticiaceae, Polyporales) species with hyphal pegs are described and illustrated. Type specimens of Corticium griseocanum and Dendrothele papillosa were examined and found to be conspecific. Two new taxa, D. americana and D. tanzaniana, are described and illustrated, and the new combination, Dendrothele andina, is proposed. A key to D. griseocana and...

Is short-term PEG-tube placement beneficial in acutely ill cognitively intact elderly patients? A proposed decision making algorithm

PubMed Central

Abraham, Rtika R; Girotra, Mohit; Wei, Jeanne Y.; Azhar, Gohar

2014-01-01

Aim Percutaneous Endoscopic Gastrostomy (PEG) tube is an important method of enteral feeding for patients who require temporary or long-term artificial nutritional support to prevent or correct disease-related malnutrition. However, there is paucity of data on the utility of short-term PEG tube placements in acute illnesses in cognitively intact elderly. Methods We present a series of seven, cognitively intact patients (age range = 72 to 93 years), who had PEG tubes placed for short periods. These patients were diagnosed with “failure to thrive” and were managed by placing a PEG tube temporarily for nutritional management. None of these patients had terminal illness or hospice eligibility and all of our patients were community dwellers. Results All our elderly patients experienced good outcomes in terms of their functional status and nutritional support. Conclusions Our series clearly supports the notion that short-term PEG tube placement in cognitively-intact elderly patients could be a successful strategy to support them during an episode of acute illness and to improve their nutritional deficits and survival. PMID:25109444

PEG-poly(amino acid) block copolymer micelles for tunable drug release.

PubMed

Ponta, Andrei; Bae, Younsoo

2010-11-01

To achieve tunable pH-dependent drug release in tumor tissues. Poly(ethylene glycol)-poly(aspartic acid) [PEG-p(Asp)] containing 12 kDa PEG and pAsp (5, 15, and 35 repeating units) were prepared. Hydrazide linkers with spacers [glycine (Gly) and 4-aminobenzoate (Abz)] were introduced to PEG-p(Asp), followed by drug conjugation [doxorubicin (DOX)]. The block copolymer-drug conjugates were either reconstituted or dialyzed in aqueous solutions to prepare micelles. Drug release patterns were observed under sink conditions at pH 5.0 and 7.4, 37°C, for 48 h. A collection of six block copolymers with different chain lengths and spacers was synthesized. Drug binding yields were 13-43.6%. The polymer-drug conjugates formed <50 nm polymer micelles irrespective of polymer compositions. Gly-introduced polymer micelles showed marginal change in particle size (40 ± 10 nm), while the size of Abz-micelles increased gradually from 10 to 40 nm as the polymer chain lengths increased. Drug release patterns of both Gly and Abz micelles were pH-dependent and tunable. The spacers appear to play a crucial role in controlling drug release and stability of polymer micelles in combination with block copolymer chain lengths. A drug delivery platform for tunable drug release was successfully developed with polymer micelles possessing spacer-modified hydrazone drug-binding linkers.

Progesterone PLGA/mPEG-PLGA Hybrid Nanoparticle Sustained-Release System by Intramuscular Injection.

PubMed

Xie, Bin; Liu, Yang; Guo, Yuting; Zhang, Enbo; Pu, Chenguang; He, Haibing; Yin, Tian; Tang, Xing

2018-02-14

To prepare sustained-release PLGA/mPEG-PLGA hybrid nanoparticles of progesterone (PRG), and evaluate the descending required administration dosage in vivo. PRG hybrid nanoparticles (PRG H-NPs) based on PLGA/mPEG-PLGA were compared with PRG nanoparticles (PRG-NPs) of pure PLGA as the matrix and PRG-oil solutions. Nanoparticles (NPs) were formed by the method of nanoemulsion, and the pharmacokinetics of the sustained-release PRG H-NPs in male Sprague dawley (SD) rats were investigated. The rats were randomly divided into four groups, each group received: single dose of PRG H-NPs (14.58 mg/kg, i.m.) and PRG-NPs (14.58 mg/kg, i.m.), repeated dosing for 7 days of PRG-oil (2.08 mg/kg, i.m.) solution (Oil-L) and a higher dosage of PRG-oil (6.24 mg/kg, i.m.) solution (Oil-H), respectively. In the pharmacokinetic test, the PRG H-NPs exhibited a comparatively good sustained-release effect against the PRG-NPs without mPEG-PLGA and PRG-oil solution. The pharmacokinetic parameters of the PRG H-NPs, PRG-NPs, Oil-L and Oil-H were AUC 0-t (ng·h·mL -1 ) 8762.1, 1546.1, 1914.5, and 12,138.9, t 1/2 (h)52.7, 44.1, 8.4 and 44.6 respectively. Owing to the modification of PEG, PRG H-NPs can act as safe delivery platforms for sustained-release of drugs with a lower dosage required.

Dissolution thermodynamics and solubility of silymarin in PEG 400-water mixtures at different temperatures.

PubMed

Shakeel, Faiyaz; Anwer, Md Khalid

2015-01-01

An isothermal method was used to measure the solubility of silymarin in binary polyethylene glycol 400 (PEG 400) + water co-solvent mixtures at temperatures T = 298.15-333.15 K and pressure p = 0.1 MPa. Apelblat and Yalkowsky models were used to correlate experimental solubility data. The mole fraction solubility of silymarin was found to increase with increasing the temperature and mass fraction of PEG 400 in co-solvent mixtures. The root mean square deviations were observed in the range of 0.48-5.32% and 1.50-9.65% for the Apelblat equation and Yalkowsky model, respectively. The highest and lowest mole fraction solubility of silymarin was observed in pure PEG 400 (0.243 at 298.15 K) and water (1.46 × 10(-5) at 298.15 K). Finally, thermodynamic parameters were determined by Van't Hoff and Krug analysis, which indicated an endothermic and spontaneous dissolution of silymarin in all co-solvent mixtures.

Enhanced bioactivity of internally functionalized cationic dendrimers with PEG cores

PubMed Central

Albertazzi, Lorenzo; Mickler, Frauke M.; Pavan, Giovanni M.; Salomone, Fabrizio; Bardi, Giuseppe; Panniello, Mariangela; Amir, Elizabeth; Kang, Taegon; Killops, Kato L.; Bräuchle, Christoph; Amir, Roey J.; Hawker, Craig J.

2012-01-01

Hybrid dendritic-linear block copolymers based on a 4-arm polyethylene glycol (PEG) core were synthesized using an accelerated AB2/CD2 dendritic growth approach through orthogonal amine/epoxy and thiol-yne chemistries. The biological activity of these 4-arm and the corresponding 2-arm hybrid dendrimers revealed an enhanced, dendritic effect with an exponential increase in cell internalization concomitant with increasing amine end-groups and low cytotoxicity. Furthermore, the ability of these hybrid dendrimers to induce endosomal escape combined with their facile and efficient synthesis makes them attractive platforms for gene transfection. The 4-arm-based dendrimer showed significantly improved DNA binding and gene transfection capabilities in comparison with the 2-arm derivative. These results combined with the MD simulation indicate a significant effect of both the topology of the PEG core and the multivalency of these hybrid macromolecules, on their DNA binding and delivery capablities. PMID:23140570

Effective mRNA Inhibition in PANC-1 Cells in Vitro Mediated via an mPEG-SeSe-PEI Delivery System.

PubMed

Zhang, Yuefeng; Yang, Bin; Liu, Yajie; Qin, Wenjie; Li, Chao; Wang, Lantian; Zheng, Wen; Wu, Yulian

2016-05-01

RNA interference (RNAi)-mediated gene therapy is a promising approach to cure various diseases. However, developing an effective, safe, specific RNAi delivery system remains a major challenge. In this study, a novel redox-responsive polyetherimide (PEI)-based nanovector, mPEG-SeSe-PEI, was developed and its efficacy evaluated. We prepared three mPEG-SeSe-PEI vector candidates for small interfering glyceraldehyde-3-phosphate dehydrogenase (siGADPH) and determined their physiochemical properties and transfection efficiency using flow cytometry and PEG11.6-SeSe-PEI polymer. We investigated the silencing efficacy of GADPH mRNA expression in PANC-1 cells and observed that PEG11.6-SeSe-PEI/siGADPH (N/P ratio=10) polyplexes possessed the appropriate size and zeta-potential and exhibited excellent in vitro gene silencing effects with the least cytotoxicity in PANC-1 cells. In conclusion, we present PEG11.6-SeSe-PEI as a potential therapeutic gene delivery system for small interfering RNA (siRNA).

Polymer-lipid-PEG hybrid nanoparticles as photosensitizer carrier for photodynamic therapy.

PubMed

Pramual, Sasivimon; Lirdprapamongkol, Kriengsak; Svasti, Jisnuson; Bergkvist, Magnus; Jouan-Hureaux, Valérie; Arnoux, Philippe; Frochot, Céline; Barberi-Heyob, Muriel; Niamsiri, Nuttawee

2017-08-01

Polymer-lipid-PEG hybrid nanoparticles were investigated as carriers for the photosensitizer (PS), 5,10,15,20-Tetrakis(4-hydroxy-phenyl)-21H,23H-porphine (pTHPP) for use in photodynamic therapy (PDT). A self-assembled nanoprecipitation technique was used for preparing two types of core polymers poly(d,l-lactide-co-glycolide) (PLGA) and poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) with lipid-PEG as stabilizer. The resulting nanoparticles had an average particle size of 88.5±3.4nm for PLGA and 215.0±6.3nm for PHBV. Both nanoparticles exhibited a core-shell structure under TEM with high zeta potential and loading efficiency. X-ray powder diffraction analysis showed that the encapsulated pTHPP molecules in polymeric nanoparticles no longer had peaks of free pTHPP in the crystalline state. The pTHPP molecules encapsulated inside the polymeric core demonstrated improved photophysical properties in terms of singlet oxygen generation and cellular uptake rate in a FTC-133 human thyroid carcinoma cell line, compared to non-encapsulated pTHPP. The pTHPP-loaded polymer-lipid-PEG nanoparticles showed better in vitro phototoxicity compared to free pTHPP, in both time- and concentration-dependent manners. Overall, this study provides detailed analysis of the photophysical properties of pTHPP molecules when entrapped within either PLGA or PHBV nanoparticle cores, and demonstrates the effectiveness of these systems for delivery of photosensitizers. The two polymeric systems may have different potential benefits, when used with cancer cells. For instance, the pTHPP-loaded PLGA system requires only a short time to show a PDT effect and may be suitable for topical PDT, while the delayed photo-induced cytotoxic effect of the pTHPP-loaded PHBV system may be more suitable for cancer solid tumors. Hence, both pTHPP-encapsulated polymer-lipid-PEG nanoparticles can be considered promising delivery systems for PDT cancer treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Polyelectrolyte complexes of hTERT siRNA and polyethyleneimine: Effect of degree of PEG grafting on biological and cellular activity.

PubMed

Safari, Fatemeh; Tamaddon, Ali M; Zarghami, Nosratollah; Abolmali, S; Akbarzadeh, Abolfazl

2016-09-01

Gene silencing by siRNA (short interfering RNA)-targeted human telomerase reverse transcriptase (hTERT) is considered a successful strategy for cancer gene therapy. Polyelectrolyte complexes (PEC) of siRNA and cationic polymers such as polyethyleneimine (PEI) have been widely used for cellular transfection; however, they demonstrate some disadvantages such as cytotoxicity and extracellular matrix restrictions. PEG grafting technology was used in an attempt to improve the biocompatibility of PECs. Considering that this technology may compromise the cellular uptake of PECs, we aimed to study the effect of degree of PEI PEGylation on the carrier cytotoxicity, cellular association, and transfection efficiency of hTERT siRNA in the lung cancer cell line A549. Activated NHS ester of methoxy PEG-COOH 5 KDa was grafted to hyperbranched PEI 25 KDa in the molar ratios of 0.2 and 1. The copolymers were characterized by (1)H-NMR spectroscopy. PECs of PEI or PEG-g-PEI with siRNA, alone or co-incubated with heparin sulfate, were studied by the ethidium bromide exclusion assay. Cytotoxicity of the polymers (PEG-g-PEI vs PEI), alone and upon formation of PEC nanoparticles with hTERT siRNA, was determined by a validated MTT assay, in comparison to a scrambled control sequence, in A549 human lung carcinoma cells. The cellular uptake of the PECs of FITC-labeled siRNA was investigated by flow cytometry at different N/P ratios, and the silencing effect of the transfected siRNA was compared to that of the control sequence for different PECs by real time RT-PCR. The cytotoxicity of PEI decreased significantly by PEG grafting, even at a low degree of PEGylation. Moreover, the nonspecific cytotoxicity of PECs decreased by PEG grafting. PECs of PEG-g-PEI showed more biologic stability on incubation with heparin sulfate. Average particle size and zeta potential of PEC nanoparticles were diminished for those of PEG-g-PEI. The cellular association was more pronounced at an N/P ratio of 2.5 for

Virioplankton 'pegylation': use of PEG (polyethylene glycol) to concentrate and purify viruses in pelagic ecosystems.

PubMed

Colombet, J; Robin, A; Lavie, L; Bettarel, Y; Cauchie, H M; Sime-Ngando, T

2007-12-01

We have described the use of Polyethylene glycol (PEG) for the precipitation of natural communities of aquatic viruses, and its comparison with the usual concentration method based on ultracentrifugation. Experimental samples were obtained from different freshwater ecosystems whose trophic status varied. Based on transmission electron microscope observations and counting of phage-shaped particles, our results showed that the greatest recovery efficiency for all ecosystems was obtained when we used the PEG protocol. On average, this protocol allowed the recovery of >2-fold more viruses, compared to ultracentrifugation. In addition, the diversity of virioplankton, based on genomic size profiling using pulsed field gel electrophoresis, was higher and better discriminated when we used the PEG method. We conclude that pegylation offers a valid, simple and cheaper alternative method to ultracentrifugation, for the concentration and the purification of pelagic viruses.

Ectopic Expression of Retrotransposon-Derived PEG11/RTL1 Contributes to the Callipyge Muscular Hypertrophy

PubMed Central

Xu, Xuewen; Ectors, Fabien; Davis, Erica E.; Pirottin, Dimitri; Cheng, Huijun; Farnir, Frédéric; Hadfield, Tracy; Cockett, Noelle; Charlier, Carole; Georges, Michel; Takeda, Haruko

2015-01-01

The callipyge phenotype is an ovine muscular hypertrophy characterized by polar overdominance: only heterozygous + Mat /CLPG Pat animals receiving the CLPG mutation from their father express the phenotype. + Mat /CLPG Pat animals are characterized by postnatal, ectopic expression of Delta-like 1 homologue (DLK1) and Paternally expressed gene 11/Retrotransposon-like 1 (PEG11/RTL1) proteins in skeletal muscle. We showed previously in transgenic mice that ectopic expression of DLK1 alone induces a muscular hypertrophy, hence demonstrating a role for DLK1 in determining the callipyge hypertrophy. We herein describe newly generated transgenic mice that ectopically express PEG11 in skeletal muscle, and show that they also exhibit a muscular hypertrophy phenotype. Our data suggest that both DLK1 and PEG11 act together in causing the muscular hypertrophy of callipyge sheep. PMID:26474044

Raman-Scattering Line Profiles of the Symbiotic Star AG Peg

NASA Astrophysics Data System (ADS)

Lee, Seong-Jae; Hyung, Siek

2017-06-01

The high dispersion Hα and Hβ line profiles of the Symbiotic star AG Peg consist of top double Gaussian and bottom components. We investigated the formation of the broad wings with Raman scattering mechanism. Adopting the same physical parameters from the photo-ionization study of Kim and Hyung (2008) for the white dwarf and the ionized gas shell, Monte Carlo simulations were carried out for a rotating accretion disk geometry of non-symmetrical latitude angles from -7° < θ < +7° to -16° < θ < +16°. The smaller latitude angle of the disk corresponds to the approaching side of the disk responsible for weak blue Gaussian profile, while the wider latitude angle corresponds to the other side of the disk responsible for the strong red Gaussian profile. We confirmed that the shell has the high gas density ˜ 109.85 cm-3 in the ionized zone of AG Peg derived in the previous photo-ionization model study. The simulation with various HI shell column densities (characterized by a thickness ΔD × gas number density nH) shows that the HI gas shell with a column density Hhi ≈ 3 - 5 × 1019 cm-2 fits the observed line profiles well. The estimated rotation speed of the accretion disk shell is in the range of 44 - 55 kms-1. We conclude that the kinematically incoherent structure involving the outflowing gas from the giant star caused an asymmetry of the disk and double Gaussian profiles found in AG Peg.

Fabrication of biodegradable PEG-PLA nanospheres for solubility, stabilization, and delivery of curcumin.

PubMed

Liang, Hongying; Friedman, Joel M; Nacharaju, Parimala

2017-03-01

Curcumin is an effective and safe anticancer agent, and also known to induce vasodilation, but its hydrophobicity limits its clinical application. In this study, a simple emulsion method was developed to prepare biodegradable poly (ethylene glycol)-poly (lactic acid) (PEG-PLA) nanospheres to encapsulate curcumin to improve its solubility and stability. The nanoparticle size was around 150 nm with a narrow size distribution. Fluorescence microscopy showed that curcumin encapsulated PEG-PLA nanospheres were taken up rapidly by Hela and MDA-MB-231 cancer cells. This novel nanoparticulate carrier may improve the bioavailability of curcumin without affecting its anticancer properties.

Preparation, structural analysis and bioactivity of ribonuclease A-albumin conjugate: tetra-conjugation or PEG as the linker.

PubMed

Li, Chunju; Lin, Qixun; Wang, Jun; Shen, Lijuan; Ma, Guanghui; Su, Zhiguo; Hu, Tao

2012-12-31

Ribonuclease A (RNase A) is a therapeutic enzyme with cytotoxic action against tumor cells. Its clinical application is limited by the short half-life and insufficient stability. Conjugation of albumin can overcome the limitation, whereas dramatically decrease the enzymatic activity of RNase A. Here, three strategies were proposed to prepare the RNase A-bovine serum albumin (BSA) conjugates. R-SMCC-B (a conjugate of four RNase A attached with one BSA) and R-PEG-B (a mono-conjugate) were prepared using Sulfo-SMCC (a short bifunctional linker) and mal-PEG-NHS (a bifunctional PEG), respectively. Mal-PEG-NHS and hexadecylamine (HDA) were used to prepare the mono-conjugate, R-HDA-B, where HDA was adopted to bind BSA. The PEG linker can elongate the proximity between RNase A and BSA. In contrast, four RNase A were closely located on BSA in R-SMCC-B. R-SMCC-B showed the lowest K(m) and the highest relative enzymatic activity and k(cat)/K(m) in the three conjugates. Presumably, the tetravalent interaction of RNase A in R-SMCC-B can increase the binding affinity to its substrate. In addition, the slow release of BSA from R-HDA-B may increase the enzymatic activity of R-HDA-B. Our study is expected to provide strategies to develop protein-albumin conjugate with high therapeutic potential. Copyright © 2012 Elsevier B.V. All rights reserved.

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

PubMed

Zhang, Zuoheng; Lin, Xubo; Gu, Ning

2017-12-01

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

NuLYTELY (PEG 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution).

PubMed

Swartz, M L

1992-02-01

NuLYTELY (PEG 3350, Sodium Chloride, Sodium Bicarbonate, and Potassium Chloride for Oral Solution), a product from Braintree Laboratories, Inc. is a modification of GoLYTELY (PEG 3350 and Electrolytes for Oral Solution) that has been found to have the same therapeutic advantages in terms of safety, efficacy, speed and patient acceptance. This product was developed to improve upon the taste of GoLYTELY. NuLYTELY represents an effective alternative for bowel cleansing prior to colonoscopy that may be more acceptable to some patients.

Current microbiology of percutaneous endoscopic gastrostomy tube (PEG tube) insertion site infections in patients with cancer.

PubMed

Rolston, Kenneth V I; Mihu, Coralia; Tarrand, Jeffrey J

2011-08-01

Percutaneous endoscopic gastrostomy (PEG) is frequently used to provide enteral access in cancer patients who are unable to swallow. Infection is an important complication in this setting. Current microbiological data are needed to guide infection prevention and treatment strategies. The microbiological records of our institution (a 550-bed comprehensive cancer center) were retrospectively reviewed over an 8-month study period in order to identify patients who developed PEG tube insertion site infections, and review their microbiological details and susceptibility/resistance data. Fifty-eight episodes of PEG tube insertion site infections were identified. Of these, 31 (53%) were monomicrobial, and the rest were polymicrobial. The most common organisms isolated were Candida species, Staphylococcus aureus, and Pseudomonas aeruginosa. All infections were local (cellulitis, complicated skin, and skin structure infections including abdominal wall abscess) with no cases of concomitant bacteremia being documented. Most of the organisms isolated were susceptible to commonly used antimicrobial agents, although some quinolone-resistant and some multidrug-resistant organisms were isolated. This retrospective study provides descriptive data regarding PEG tube insertion site infections. These data have helped us update institutional guidelines for infection prevention and treatment as part of our focus on antimicrobial stewardship.

Pegademase bovine (PEG-ADA) for the treatment of infants and children with severe combined immunodeficiency (SCID).

PubMed

Booth, Claire; Gaspar, H Bobby

2009-01-01

Adenosine deaminase deficiency (ADA) is a rare, inherited disorder of purine metabolism characterized by immunodeficiency, failure to thrive and metabolic abnormalities. A lack of the enzyme ADA allows accumulation of toxic metabolites causing defects of both cell mediated and humoral immunity leading to ADA severe combined immune deficiency (SCID), a condition that can be fatal in early infancy if left untreated. Hematopoietic stem cell transplant is curative but is dependent on a good donor match. Other therapeutic options include enzyme replacement therapy (ERT) with pegademase bovine (PEG-ADA) and more recently gene therapy. PEG-ADA has been used in over 150 patients worldwide and has allowed stabilization of patients awaiting more definitive treatment with hematopoietic stem cell transplant. It affords both metabolic detoxification and protective immune function with patients remaining clinically well, but immune reconstitution is often suboptimal and may not be long lived. We discuss the pharmacokinetics, immune reconstitution, effects on systemic disease and side effects of treatment with PEG-ADA. We also review the long-term outcome of patients receiving ERT and discuss the role of PEG-ADA in the management of infants and children with ADA-SCID, alongside other therapeutic options.

Addition of Lubiprostone to polyethylene glycol(PEG) enhances the quality & efficacy of colonoscopy preparation: a randomized, double-blind, placebo controlled trial.

PubMed

Banerjee, Rupa; Chaudhari, Hrushikesh; Shah, Nirish; Saravanan, Arjunan; Tandan, Manu; Reddy, D Nageshwar

2016-10-13

Adequate bowel preparation is an essential prerequisite for complete mucosal visualization during colonoscopy. Polyethylene glycol (PEG) solutions are commonly used. However the large volume of the solution is often poorly tolerated. Addition of Lubiprostone (LB) could improve the adequacy of standard PEG preparation & reduce requirement. The aims to assess adequacy of PEG preparation with addition of single dose LB (24mcg) vs placebo and efficacy of reduced dose PEG + LB compared with full dose PEG + LB. Single center prospective double blind randomized controlled trial. Part I: 442 patients for colonoscopy randomized to receive placebo (GrA) or single dose of LB (GrB) prior to PEG preparation. Quality of bowel preparation graded 0-9 according to Boston Bowel Preparation Scale (BBPS). BBPS-9: excellent and BBPS 0-4: repeat procedure. Part II: 146 patients randomized to receive LB + 1.5 L PEG (GrC; 75) or LB + 1 L PEG (GrD; 71). BBPS score compared with GrB (2 L PEG). Part I: 442 patients (221 GrA & 221 Gr B). LB resulted in significant improvement in total BBPS (7.44 + 0.14 vs. 6.36 + 0.16, p < 0.0001). 66.5 % Gr B vs 38 % Gr A had excellent prep; 42.5 % GrB vs 24 % GrA had adequate prep. Repeat procedure needed 9.5 % Gr B vs 16.7 % Gr A (P < 0.01). Part II: No difference in BBPS scores with lower doses (Gr C&D) compared to standard (GrB) (Mean BBPS 7.44 + 0.14 GrA,7.30 + 0.25 GrC;7.25 + 0.26 GrD;p >0.05). Single dose LB prior to PEG significantly enhanced bowel preparation compared to PEG alone. There was no significant difference in quality of preparation with lower doses of PEG when combined with LB. The study protocol was approved by institutional review board and the trial was registered on March 22, 2011 with clinicaltrials.gov ( NCT01324284 ).

75 FR 14375 - Airworthiness Directives; Pratt & Whitney (PW) PW4000 Series Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-25

...) PW4000 Series Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of..., PW4156, PW4156A, PW4158, PW4164, PW4168, PW4168A, PW4460, and PW4462 turbofan engines. This proposed AD..., PW4156, PW4156A, PW4158, PW4164, PW4168, PW4168A, PW4460, and PW4462 turbofan engines. These engines are...

Defined PEG smears as an alternative approach to enhance the search for crystallization conditions and crystal-quality improvement in reduced screens

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

Chaikuad, Apirat, E-mail: apirat.chaikuad@sgc.ox.ac.uk; Knapp, Stefan; Johann Wolfgang Goethe-University, Building N240 Room 3.03, Max-von-Laue-Strasse 9, 60438 Frankfurt am Main

An alternative strategy for PEG sampling is suggested through the use of four newly defined PEG smears to enhance chemical space in reduced screens with a benefit towards protein crystallization. The quest for an optimal limited set of effective crystallization conditions remains a challenge in macromolecular crystallography, an issue that is complicated by the large number of chemicals which have been deemed to be suitable for promoting crystal growth. The lack of rational approaches towards the selection of successful chemical space and representative combinations has led to significant overlapping conditions, which are currently present in a multitude of commercially availablemore » crystallization screens. Here, an alternative approach to the sampling of widely used PEG precipitants is suggested through the use of PEG smears, which are mixtures of different PEGs with a requirement of either neutral or cooperatively positive effects of each component on crystal growth. Four newly defined smears were classified by molecular-weight groups and enabled the preservation of specific properties related to different polymer sizes. These smears not only allowed a wide coverage of properties of these polymers, but also reduced PEG variables, enabling greater sampling of other parameters such as buffers and additives. The efficiency of the smear-based screens was evaluated on more than 220 diverse recombinant human proteins, which overall revealed a good initial crystallization success rate of nearly 50%. In addition, in several cases successful crystallizations were only obtained using PEG smears, while various commercial screens failed to yield crystals. The defined smears therefore offer an alternative approach towards PEG sampling, which will benefit the design of crystallization screens sampling a wide chemical space of this key precipitant.« less

Co-encapsulated resveratrol and quercetin in chitosan and peg modified chitosan nanoparticles: For efficient intra ocular pressure reduction.

PubMed

Natesan, Subramanian; Pandian, Saravanakumar; Ponnusamy, Chandrasekar; Palanichamy, Rajaguru; Muthusamy, Sivakumar; Kandasamy, Ruckmani

2017-11-01

Natural anti-oxidants resveratrol (RES) and quercetin (QUR) posses the ability to reduce intra ocular pressure efficiently. Concurrent administration of RES and QUR was able to enhance the bioavailability of RES. Present research work describes upsurge of QUR in RES loaded chitosan (CS) nanoparticles (NPs) and polyethylene glycol (PEG) modified CS NPs for improved delivery and synergic effects on reducing intra ocular pressure for the treatment of glaucoma. CS NPs and PEG modified CS NPs were prepared by ionic gelation of tripolyphosphate and CS. The synthesised NPs were spherical in shape and RES entrapment and loading efficiency in the formulation decreased with increasing PEG concentration. Particle size of the formulation increased while incorporating PEG and drugs. The crystalline nature of RES and QUR changed in the NPs and that was confirmed by XRD study. Free radical neutralising efficiency improved while incorporating QUR in the formulation. Ex-vivo corneal permeation of RES was higher from RES and QUR loaded formulation than RES alone containing NPs and free RES dispersion. RES and QUR loaded PEG modified CS NPs showed sustained and enhanced reduction of intra ocular pressure (5.5±0.5mmHg) in normotensive rabbits. Copyright © 2017 Elsevier B.V. All rights reserved.

Examination of the Perceived Efficacy and Goal Setting System (PEGS) with children with disabilities, their parents, and teachers.

PubMed

Missiuna, Cheryl; Pollock, Nancy; Law, Mary; Walter, Stephen; Cavey, Nina

2006-01-01

The Perceived Efficacy and Goal Setting System (PEGS) is an instrument and a process that enables children with disabilities to reflect on their ability to perform everyday occupations and to identify goals for occupational therapy intervention. In this study, 117 children with disabilities in grades 1-3 completed the PEGS with occupational therapists who work in school settings. Children from 6-9 years of age with a variety of disabilities were able to self-report perceptions of their effectiveness performing 24 activities that would be expected of them each day. Parents and teachers, who completed a parallel questionnaire, rated their abilities lower than the children did. The School Function Assessment, a measure of the amount and type of support required for school participation, had low correlations with the Parent and Teacher PEGS questionnaires and did not correlate with the Child PEGS. No differences in perceived efficacy were found for children across grades or gender; however, differences were found across types of disabilities. Children were able to use the perceived efficacy information to identify and prioritize goals for intervention and these goals remained stable 2 weeks later. Occupational therapists can use the PEGS within a client-centered practice to help the child set goals for therapy and to incorporate explicitly the perspectives of parents and teachers.

Control of Dielectric Constant and Anti-Bacterial Activity of PVA-PEG/x-SnO2 Nanofiber

NASA Astrophysics Data System (ADS)

Diantoro, M.; Sari, L. A.; Istirohah, T.; Kusumawati, A. D.; Nasikhudin; Sunaryono

2018-05-01

Research in the utilization of organic natural materials for electronic devices and for the biological application becoming extensively studied. We report a comprehensive review of the role of SnO2 nanoparticle and the effect of light intensity on toxicity properties, antibacterial activity, microstructure and electrical properties of PVA-PEG nanofiber films. The PVA-PEG/SnO2 nanofiber structure has been successfully fabricated on the ITO-glass substrate. Characterization was performed on samples using FTIR, XRD, SEM, toxicity and antibacterial tests, as well as LCR measurement. The presence of various light intensities has also measured the dielectric constant. The addition of SnO2 nanoparticle influenced the structure of the PVA-PEG/SnO2 nanofiber bonding functional group indicated by the appearance of Sn-O-Sn peaks at 648.08 cm-1 and 958 cm-1 wavenumbers. The addition of SnO2 nanoparticles affects the grain size of SnO2. Addition of SnO2 nanoparticles increases the detected toxicity voltage but is still below the threshold. It means the compound is not toxic, or safe to use in the body. The film lacks the antibacterial power of S. Aurelius. The addition of nanoparticles SnO2 increases the dielectric constant but decreases with increasing frequency of input voltage and the intensity of light employed to PVA-PEG/SnO2 nanofiber. The application of the light intensity reduces the dielectric constant of the PVA-PEG/SnO2 nanofiber in all nanoparticle doping ranges.

Co-delivery of hydrophilic and hydrophobic drugs by micelles: a new approach using drug conjugated PEG-PCLNanoparticles.

PubMed

Danafar, Hossein; Rostamizadeh, Kobra; Davaran, Soodabeh; Hamidi, Mehrdad

2017-11-01

Co-delivery strategy has been proposed to minimize the amount of each drug and to achieve the synergistic effect for cancer therapies. A conjugate of the antitumor drug, doxorubicin, with diblock methoxy poly (ethylene glycol)-poly caprolactone (mPEG-PCL) copolymer was synthesized by the reaction of mPEG-PCL copolymer with doxorubicin in the presence of p-nitrophenylchloroformate. The conjugated copolymer was characterized in vitro by 1 H-NMR, FTIR, DSC and GPC techniques. Then, the doxorubicin conjugated mPEG-PCL(DOX-mPEG-PCL) was self-assembled into micelles in the presence of curcumin in aqueous solution. The resulting micelles were characterized further by various techniques such as dynamic light scattering (DLS) and atomic force microscopy (AFM).The encapsulation efficiency of doxorubicin and curcumin were 82.31 ± 3.32 and 78.15 ± 3.14%, respectively. The results revealed that the micelles formed by the DOX-mPEG-PCL with and without curcumin have spherical structure with average size of 116 and 134 nm respectively. The release behavior of curcumin and doxorubicin loaded to micelles were investigated in a different media. The release rate of micelles consisted of the conjugated copolymer was pH dependent as it was higher at lower pH than in neutral condition. Another feature of the conjugated micelles was a sustained release profile. The cytotoxicity of micelles were evaluated by MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, atetrazole) assay on lung cancer A549 cell lines. In vitro cytotoxicity assay showed that the mPEG-PCL copolymer did not affect the growth of A549 cells. The cytotoxic activity of the micelles against A549 cells was greater than free doxorubicin and free curcumin.

Crystallization of multiple forms of bovine seminal ribonuclease in the liganded and unliganded state

NASA Astrophysics Data System (ADS)

Sica, F.; Adinolfi, S.; Berisio, R.; De Lorenzo, C.; Mazzarella, L.; Piccoli, R.; Vitagliano, L.; Zagari, A.

1999-01-01

Bovine seminal ribonuclease (BS-RNase) is an intriguing homodimeric enzyme which exists as two conformational isomers, characterized by distinct catalytic and biological properties, referred to as M×M and M=M. Reduction of inter-chain disulfide bridges produces a stable monomeric derivative (M) which is still active. This paper reports the screening and optimization of crystallization conditions for growing single diffraction-quality crystals for the various BS-RNase forms. The crystallization trials were performed using both the vapor diffusion and microbatch methods. The M×M dimer was crystallized in the free form from polyethylene glycol (PEG) 4000 at pH 8.5 and as a complex with the substrate analog uridylyl(2'- 5')guanosine (UpG) from an unbuffered ammonium sulfate (AS) solution. These two crystal types diffract X-rays to 2.5 and 1.9 Å resolution, respectively. Two different crystal types were obtained both for the M=M dimer and for the monomeric derivative. (M=M)a crystals, grown from PEG 4000 (8% w/v) at pH 5.6, diffract X-rays to 4.0 Å. At higher PEG concentration (15% w/v) a different crystal type was obtained, (M=M)b, which showed a better diffraction limit (2.5 Å). For the monomer, type (M)a and (M)b crystals, diffracting X-rays to 2.5 Å resolution, were obtained from AS at pH 6.5 and from PEG 4000 at pH 8.5, respectively. A comparison with previously crystallized forms of the dimer M×M and its complexes with uridylyl(2'-5')adenosine and 2'-deoxycytidylyl(3'-5')-2'-deoxyadenosine is also presented. The three-dimensional structure analysis of (M×M)·UpG and (M=M)b is in progress.

Volar fixed-angle plating of extra-articular distal radius fractures--a biomechanical analysis comparing threaded screws and smooth pegs.

PubMed

Weninger, Patrick; Dall'Ara, Enrico; Leixnering, Martin; Pezzei, Christoph; Hertz, Harald; Drobetz, Herwig; Redl, Heinz; Zysset, Philippe

2010-11-01

Distal radius fractures represent the most common fractures in adult individuals. Volar fixed-angle plating has become a popular modality for treating unstable distal radius fractures. Most of the plates allow insertion of either threaded locking screws or smooth locking pegs. To date, no biomechanical studies compare locking screws and pegs under axial and torsional loading. Ten Sawbones radii were used to simulate an AO/OTA A3 fracture. Volar fixed-angle plates (Aptus Radius 2.5, Medartis, Switzerland) with threaded locking screws (n = 5) or smooth locking pegs (n = 5) were used to fix the distal metaphyseal fragment. Each specimen was tested under axial compression and under torsional load with a servohydraulic testing machine. Qualitative parameters were recorded as well as axial and torsional stiffness, torsion strength, energy absorbed during monotonic loading and energy absorbed in one cycle. Axial stiffness was comparable between both groups (p = 0.818). If smooth pegs were used, a 17% reduction of torsional stiffness (p = 0.017) and a 12% reduction of minimum torque (p = 0.012) were recorded. A 12% reduction of energy absorbed (p = 0.013) during monotonic loading and unloading was recorded if smooth pegs were used. A 34% reduction of energy absorbed in one cycle (p < 0.007) was recorded if threaded screws were used. Sliding of the pegs out of the distal radius metaphyses of the synthetic bones was recorded at a mean torque of 3.80 Nm ± 0.19 Nm. No sliding was recorded if threaded screws were used. According to the results of this study using Sawbones, volar fixed-angle plates with threaded locking screws alone are mechanically superior to volar fixed-angle plates with smooth locking pegs alone under torsional loading.

Toxicity of PEG-Coated CoFe2O4 Nanoparticles with Treatment Effect of Curcumin

NASA Astrophysics Data System (ADS)

Akhtar, Shahnaz; An, Wenzhen; Niu, Xiaoying; Li, Kang; Anwar, Shahzad; Maaz, Khan; Maqbool, Muhammad; Gao, Lan

2018-02-01

In this work, CoFe2O4 nanoparticles coated with polyethylene glycol (PEG) were successfully synthesized via a hydrothermal technique. Morphological studies of the samples confirmed the formation of polycrystalline pure-phase PEG-CoFe2O4 nanoparticles with sizes of about 24 nm. Toxicity induced by CoFe2O4 nanoparticles was investigated, and biological assays were performed to check the toxicity effects of CoFe2O4 nanoparticles. Moreover, the healing effect of toxicity induced in living organisms was studied using curcumin and it was found that biochemical indexes detoxified and improved to reach its normal level after curcumin administration. Thus, PEG-coated CoFe2O4 synthesized through a hydrothermal method can be utilized in biomedical applications and curcumin, which is a natural chemical with no side effects, can be used for the treatment of toxicity induced by the nanoparticles in living organisms.

Designing an extended release waxy matrix tablet containing nicardipine–hydroxy propyl β cyclodextrin complex

PubMed Central

Al-Zein, Hind; Sakeer, Khalil; Alanazi, Fars K.

2011-01-01

Aim The current study aimed to prepare a sustained release tablet for a drug which has poor solubility in alkaline medium using complexation with cyclodextrin. Nicardipine hydrochloride (NC) a weak basic drug was chosen as a model drug for this study. Method Firstly the most suitable binary system NC-HPβCD was selected in order to improve drug solubility in the intestinal media and then embedding the complexed drug into a plastic matrix, by fusion method, consists of glycerol monostearate (GMS) as an inert waxy substance and polyethylene glycol 4000 (PEG4000) as a channeling agent, after that the final solid dispersion [(NC:HPβCD):GMS:PEG4000] which was prepared at different ratios was mixed with other excipients, avicel PH101, lactose, and talc, to get a tablet owning dissolution profile complying with the FDA and USP requirements for the extended release solid dosage forms. Results Infrared spectroscopy (IR), differential scanning colorimetry (DSC), polarized microscopy and X-ray diffractometry proved that the coevaporation technique was effective in preparing amorphous cyclodextrin complexes with NC and trapping of NC within the HPβCD cavity by dissolving both in ethanol and evaporate the solvent using a rotavapor at 65 °C. Dissolution profile of NC enhanced significantly in pH 6.8 from NC:HPβCD inclusion complex prepared by the rotavapor (t-test Student p < 0.05). The release of NC from tablet containing [(NC:HPβCD):GMS:PEG4000] [(1):0.75:0.5] (w/w/w) solid dispersion (F8) was complying with the FDA dissolution requirements for extended release dosage forms, and studying the kinetics of the release showed that the diffusional contribution is the major factor controlling the drug release from that formula. Conclusion The prepared waxy matrix tablet containing NC complexes with CD shows promising results as extended release tablets. PMID:23960765

Xingnaojing mPEG2000-PLA modified microemulsion for transnasal delivery: pharmacokinetic and brain-targeting evaluation.

PubMed

Wen, Ran; Zhang, Qing; Xu, Pan; Bai, Jie; Li, Pengyue; Du, Shouying; Lu, Yang

2016-01-01

Xingnaojing microemulsion (XNJ-M) administered intranasally is used for stroke treatment. In order to decrease the XNJ-M-induced mucosal irritation, XNJ-M modified by mPEG2000-PLA (XNJ-MM) were prepared in a previous work. The present work aimed to assess the impact of mPEG2000-PLA on pharmacokinetic features and brain-targeting ability of XNJ-M. The bioavailability and brain-target effects of borneol and geniposide in XNJ-M and XNJ-MM were compared in mice after intravenous (i.v.) and intranasal (i.n.) administrations. Gas chromatography, high-performance liquid chromatography, and ultra-performance liquid chromatography/tandem mass spectrometry methods were developed for the quantification of borneol and geniposide. Blood and brain samples were collected from mice at different time points after i.v. and i.n. treatments with borneol at 8.0 mg/kg, geniposide at 4.12 mg/kg. In addition, near-infrared fluorescence dye, 1,1'-dioctadecyl-3,3,3',3'-tetramethyl indotricarbocyanine iodide was loaded into microemulsions to evaluate the brain-targeting ability of XNJ-M and XNJ-MM by near-infrared fluorescence imaging in vivo and ex vivo. For XNJ-M and XNJ-MM, the relative brain targeted coefficients (Re) were 134.59% and 198.09% (borneol), 89.70% and 188.33% (geniposide), respectively. Besides, significant near-infrared fluorescent signal was detected in the brain after i.n. administration of microemulsions, compared with that of groups for i.v. administration. These findings indicated that mPEG2000-PLA modified microemulsion improved drug entry into blood and brain compared with normal microemulsion: the introduction of mPEG2000-PLA in microemulsion resulted in brain-targeting enhancement of both fat-soluble and water-soluble drugs. These findings provide a basis for the significance of mPEG2000-PLA addition in microemulsion, defining its effects on the drugs in microemulsion.

Efficient SO2 capture by amine functionalized PEG.

PubMed

Yang, Dezhong; Hou, Minqiang; Ning, Hui; Zhang, Jianling; Ma, Jun; Han, Buxing

2013-11-07

Polyethylene glycols (PEGs) are a class of non-toxic, non-volatile, biocompatible, and widely available polymers. In this work, we synthesized N-ethyl-N-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)-2-aminoethanol (EE3AE) that combines the properties of PEG and amines, and N-decyl-N-ethyl-2-aminoethanol (DEAE). Their performances to capture SO2 were studied at different temperatures, pressures, and absorption times. The interaction between the absorbents and SO2 were characterized by NMR and FTIR techniques. It was demonstrated that both EE3AE and DEAE could absorb SO2 efficiently, and there existed chemical and physical interactions between the absorbents and SO2. In particular, the absorption capacity of EE3AE could be as high as 1.09 g SO2 per g EE3AE at 1 atm. The absorption capacity of EE3AE was much larger than that of DEAE because the ether group in the EE3AE interacted with SO2 more strongly than the alkyl group in the DEAE. The SO2 absorbed by EE3AE could be stripped out by bubbling N2 or by applying a vacuum and the EE3AE could be reused. Moreover, both absorbents exhibited a high SO2-CO2 selectivity.

A randomized, controlled, double-blind trial of the adjunct use of Clebopride in polyethylene glycol electrolyte (PEG) solution for colonoscopy preparation.

PubMed

Abdullah, Murdani; Rani, A Aziz; Fauzi, Achmad; Syam, Ari Fahrial; Makmun, Dadang; Simadibrata, Marcellus; Manan, Chudahman; Harjodisastro, Daldiyono

2010-01-01

To study the benefit of Clebopride as an adjuvant in polyethylene glycol electrolyte (PEG) solution for colonoscopy preparation. Eighty one adult patients who underwent colonoscopy examination were recruited in this randomized double blind controlled study. First group received PEG and placebo, whereas second group received PEG and Clebopride. Two litres of PEG was taken at night before colonoscopy. The acceptability and tolerability of bowel preparation were assessed through interview method. The efficacy of bowel preparation was assessed using Aronchick's Criteria. In terms of acceptability, 64 patients (31 patients from placebo group vs 33 patients from Clebopride group) were able to drink two litres of PEG solution. Sixty patients (29 patients from placebo group and 31 patients from Clebopride group) were willing to accept PEG solution for their next bowel preparation. On the term of tolerability, nausea, abdominal distension, and borborygmus were more frequent in the placebo group (34.2% vs 27.9%; 44.7% vs 32.6%; 26.3% vs 4.6% respectively). However, only the difference at the incidence of borborygmus that was statistically significant (p<0.05). On the terms of efficacy, both groups showed a comparable bowel preparation quality with 88.4% of bowel preparation in Clebopride group and 81.6% of bowel preparation in placebo group were optimal (p = 0.585). The adjunct use of Clebopride in PEG solution for colonoscopy preparations tends to increase the acceptability, tolerability, and efficacy. The presence of borborygmus was significantly lower in the Clebopride group.

Life and Operating Range Extension of the BPT-4000 Qualification Model Hall Thruster

NASA Technical Reports Server (NTRS)

Welander, Ben; Carpenter, Christian; deGrys, Kristi; Hofer, Richard R.; Randolph, Thomas M.; Manzella, David H.

2006-01-01

Following completion of the 5,600 hr qualification life test of the BPT-4000 4.5 kW Hall Thruster Propulsion System, NASA and Aerojet have undertaken efforts to extend the qualified operating range and lifetime of the thruster to support a wider range of NASA missions. The system was originally designed for orbit raising and stationkeeping applications on military and commercial geostationary satellites. As such, it was designed to operate over a range of power levels from 3 to 4.5 kW. Studies of robotic exploration applications have shown that the cost savings provided by utilizing commercial technology that can operate over a wider range of power levels provides significant mission benefits. The testing reported on here shows that the 4.5 kW thruster as designed has the capability to operate efficiently down to power levels as low as 1 kW. At the time of writing, the BPT-4000 qualification thruster and cathode have accumulated over 400 hr of operation between 1 to 2 kW with an additional 600 hr currently planned. The thruster has demonstrated no issues with longer duration operation at low power.

Honeycomb-like PLGA- b-PEG Structure Creation with T-Junction Microdroplets.

PubMed

Gultekinoglu, Merve; Jiang, Xinyue; Bayram, Cem; Ulubayram, Kezban; Edirisinghe, Mohan

2018-06-04

Amphiphilic block copolymers are widely used in science owing to their versatile properties. In this study, amphiphilic block copolymer poly(lactic- co-glycolic acid)- block-poly(ethylene glycol) (PLGA- b-PEG) was used to create microdroplets in a T-junction microfluidic device with a well-defined geometry. To compare interfacial characteristics of microdroplets, dichloromethane (DCM) and chloroform were used to prepare PLGA- b-PEG solution as an oil phase. In the T-junction device, water and oil phases were manipulated at variable flow rates from 50 to 300 μL/min by increments of 50 μL/min. Fabricated microdroplets were directly collected on a glass slide. After a drying period, porous two-dimensional and three-dimensional structures were obtained as honeycomb-like structure. Pore sizes were increased according to increased water/oil flow rate for both DCM and chloroform solutions. Also, it was shown that increasing polymer concentration decreased the pore size of honeycomb-like structures at a constant water/oil flow rate (50:50 μL/min). Additionally, PLGA- b-PEG nanoparticles were also obtained on the struts of honeycomb-like structures according to the water solubility, volatility, and viscosity properties of oil phases, by the aid of Marangoni flow. The resulting structures have a great potential to be used in biomedical applications, especially in drug delivery-related studies, with nanoparticle forming ability and cellular responses in different surface morphologies.

Comparison of polyethylene glycol with and without electrolytes in the treatment of constipation in elderly institutionalized patients: a randomized, double-blind, parallel-group study.

PubMed

Seinelä, Lauri; Sairanen, Ulla; Laine, Tarmo; Kurl, Sangita; Pettersson, Tiina; Happonen, Pertti

2009-01-01

Polyethylene glycol (PEG) is a commonly used osmotic laxative. PEG with electrolytes is mixed with water, but PEG without electrolytes can also be mixed with, for example, juice, coffee or tea, making it more palatable. Laxatives, including PEG, are commonly used by the elderly, particularly those living in institutions. Few clinical studies, however, have investigated the use of PEG in this population. To test whether PEG 4000 without electrolytes (hypotonic PEG) is at least as effective and safe as PEG 4000 with electrolytes (isotonic PEG) in elderly institutionalized constipated patients. The acceptability of the treatments was also compared. This randomized, double-blind, parallel-group study was conducted at ten private assisted-living facilities or communal nursing homes in Finland. Eligible patients were required to have used isotonic PEG at a stable dose without any other treatment for constipation (except for Plantago ovata seeds) for at least 2 weeks prior to a run-in period. After the 1-week run-in, 62 patients (mean age 86 years; range 66-99 years) were randomly either switched to receive hypotonic PEG or continued to receive isotonic PEG, both dissolved in water, 12 g once or twice daily or once every other day, for 4 weeks. Stool frequency, stool consistency, stool straining and gastrointestinal symptoms were recorded. Safety laboratory tests were conducted before and after the treatment period. Acceptability was assessed at the end of the study. At week 4, mean (SD) weekly stool frequencies in the hypotonic and isotonic PEG groups were 8.5 (4.5) and 8.4 (3.6), respectively. The mean stool frequency ratio (95% CI) was 0.90 (0.74, 1.10); thus, the PEG products were considered equally effective. At week 4, the proportion of patients with soft or normal stool consistency was higher in the hypotonic PEG group than in the isotonic PEG group (70% vs 52%), but this difference was not statistically significant. There were no differences between the groups in

The role of transforming growth factor-beta in PEG-rHuMGDF-induced reversible myelofibrosis in rats.

PubMed

Yanagida, M; Ide, Y; Imai, A; Toriyama, M; Aoki, T; Harada, K; Izumi, H; Uzumaki, H; Kusaka, M; Tokiwa, T

1997-12-01

Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) injected at a suprapharmacologic dose (100 microg/kg) daily for 5 d in normal rats caused marked increases in marrow megakaryocytes and platelet counts at 6-8 d followed by gradual decreases to control levels at 10-20 d. Interestingly, in addition to the expected thrombopoiesis, PEG-rHuMGDF was associated with myelofibrosis with a predominance of reticulin fibres at day 10 followed by complete normalization by day 20. At 6-8 d, the levels of transforming growth factor-beta1 (TGF-beta1) in the extracellular fluid of the marrow, the platelet poor plasma, and the platelet extract were increased 23-, 7- and 2-fold, respectively. The elevated levels of TGF-beta1 were gradually reduced to baseline levels at 13-20 d in accordance with the normalization of myelofibrosis and thrombopoiesis. An ultrastructural analysis showed that large fragments of megakaryocytes were deposited in the marrow parenchyma of PEG-rHuMGDF-treated rats at day 6. PEG-rHuMGDF administration at pharmacologic doses (1 and 10 microg/kg) did not induce the deposition of reticulin fibres in the marrow. These findings suggest that TGF-beta1 leaked from megakaryocytes is involved in the development of the PEG-rHuMGDF-induced myelofibrosis and that this is a reversible process related to the regulation of the excess production of platelets.

Immunocytometric quantitation of foeto-maternal haemorrhage with the Abbott Cell-Dyn CD4000 haematology analyser.

PubMed

Little, B H; Robson, R; Roemer, B; Scott, C S

2005-02-01

This study evaluated the extended use of a haematology analyser (Abbott Cell-Dyn CD4000) for the immunofluorescent enumeration of foeto-maternal haemorrhage (FMH) with fluorescein isothiocyanate-labelled monoclonal anti-RhD. Method performance was assessed with artificial FMH standards, and a series of 44 clinical samples. Within run precision was <15% (coefficient of variation, CV) for FMH volumes of 3 ml and above, 18.8% at an FMH volume of 2 ml and 31.7% at an FMH volume of 1 ml. Linearity analysis showed excellent agreement (observed FMH% = 0.98x expected FMH% + 0.02), and a close relationship (R(2) = 0.99) between observed and expected FMH percentages. The lower limit of quantification of the CD4000 (SRP-Ret) method with a maximum CV of 15% was 1.6 ml, and the limit of detection was <1 ml. Parallel Kleihauer-Betke test (KBT) assessments of FMH standards showed an overall trend for higher KBT values (observed = 1.25x expected - 0.38). At an FMH level of 4 ml, KBT observer estimates ranged from 0.57 to 11.94 ml with a mean inter-observer CV of 63%. For 44 clinical samples, there was decision point agreement between KBT and SRP-Ret results for 42 samples with an FMH of <2 ml. Analysis in the low FMH range (<1 ml) showed that small volume foetal leaks could be detected with the SRP-Ret method in most of 23 samples with negative KBT results. CD4000 SRP-Ret method performance for FMH determination was similar to that reported for flow cytometry.

Effect of PEG and water-soluble chitosan coating on moxifloxacin-loaded PLGA long-circulating nanoparticles.

PubMed

Mustafa, Sanaul; Devi, V Kusum; Pai, Roopa S

2017-02-01

Moxifloxacin (MOX) is a Mycobacterium tuberculosis DNA gyrase inhibitor. Due to its intense hydrophilicity, MOX is cleared from the body within 24 h and required for repetitive doses which may then result in hepatotoxicity and acquisition of MOX resistant-TB, related with its use. To overcome the aforementioned limitations, the current study aimed to develop PLGA nanoparticles (PLGA NPs), to act as an efficient carrier for controlled delivery of MOX. To achieve a substantial extension in blood circulation, a combined design, affixation of polyethylene glycol (PEG) to MOX-PLGA NPs and adsorption of water-soluble chitosan (WSC) (cationic deacetylated chitin) to particle surface, was rose for surface modification of NPs. Surface modified NPs (MOX-PEG-WSC NPs) were prepared to provide controlled delivery and circulate in the bloodstream for an extended period of time, thus minimizing dosing frequency. In vivo pharmacokinetic and in vivo biodistribution following oral administration were investigated. NP surface charge was closed to neutral +4.76 mV and significantly affected by the WSC coating. MOX-PEG-WSC NPs presented striking prolongation in blood circulation, reduced protein binding, and long-drawn-out the blood circulation half-life with resultant reduced liver sequestration vis-à-vis MOX-PLGA NPs. The studies, therefore, indicate the successful formulation development of MOX-PEG-WSC NPs that showed sustained release behavior from nanoparticles which indicates low frequency of dosing.

X-ray Spectral Analysis of the Cataclysmic Variable LS Peg using XMM-Newton Observatory Data

NASA Astrophysics Data System (ADS)

Talebpour Sheshvan, N.; Nabizadeh, A.; Balman, S.

2017-10-01

LS Peg is a Cataclysmic Variable (CV) suggested as Intermediate Polar (IP) because of similar properties to those observed in IP systems. We used archival XMM-Newton observation of LS Peg in order to study the X-ray characteristics of the system. We show LS Peg light curves in several different energy bands, and discuss about orbital modulations and power spectral analysis. Unlike the previous spectral analysis of the EPIC-MOS data by fitting a hot optically thin plasma emission model with a single temperature, we simultaneously fit EPIC spectrum (pn+MOS) using a composite model of absorption (tbabs) along with two different partial covering absorbers plus a multi-temperature plasma emission component in XSPEC. In addition, we find a Gaussian emission line at 6.4 keV. For LS Peg the maximum temperature of the plasma distribution is found to be ˜ 17.8 keV with a luminosity of ˜ 7.4×10^{32}erg s^{-1} translating to an accretion rate of ˜ 1.7×10 ^{-10} M_{⊙} yr^{-1}. We present spectra for orbital minimum and orbital maximum. In addition, we use SWIFT observations of the source in order to make a comparison. We elaborate on the geometry of accretion and absorption in the X-ray emitting region with articulation on the magnetic nature.

pH-sensitive stearoyl-PEG-poly(methacryloyl sulfadimethoxine) decorated liposomes for the delivery of gemcitabine to cancer cells.

PubMed

Bersani, Sara; Vila-Caballer, Marian; Brazzale, Chiara; Barattin, Michela; Salmaso, Stefano

2014-11-01

Novel, acid-sensitive liposomes that respond to physiopathological pH for tumour targeting applications were obtained by surface decoration with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)] (mPEG-DSPE) and stearoyl-poly(ethylene glycol)-poly(methacryloyl sulfadimethoxine) copolymer (stearoyl-PEG-polySDM). The pH-sensitive stearoyl-PEG-polySDM copolymer contained an average of seven methacryloyl sulfadimethoxines per molecule and was found to possess an apparent pKa of 7.2. Preliminary cloud point studies showed that the hydrophilic/hydrophobic copolymer conversion occurred at pH 7.0. The copolymer was soluble above pH 7.0 and underwent aggregation at lower pH. Liposome formulations were prepared with 0.2:0.6:100, 0.5:1.5:100 and 1:3:100 mPEG-DSPE/stearoyl-PEG-polySDM/lipids molar ratios. All of the liposome formulations were stable at pH 7.4, even in the presence of foetal bovine serum, but they underwent rapid size increase at pH 6.5. TEM analysis showed that, at pH 6.5, the formulations coated with a stearoyl-PEG-polySDM/lipids molar ratio greater than 1:100 underwent aggregation. At pH 7.4, the liposomes showed negative zeta potential that significantly decreased after incubation at pH 6.5. Cell-culture studies indicated that the liposomes were not toxic up to 10mg/mL. Fluorescence spectroscopy, cytofluorimetry and confocal microscopy showed that at pH 6.5, the incubation of MCF-7 tumour cells with fluorescein-labelled 1:3:100 mPEG-DSPE/stearoyl-PEG-polySDM/lipids molar ratio liposomes resulted in time-dependent cell association, while at pH 7.4 the cell interaction was significantly lower. The same pH-responsive liposome formulation loaded with gemcitabine (98.2±4.7nmol gemcitabine/lipid μmol loading capacity) was stable at pH 7.4 for several hours, while at pH 6.5 it rapidly aggregated. At pH 6.5, these liposomes displayed higher cytotoxicity than at pH 7.4 or compared to non-responsive control liposomes at both incubation

YY1 as a controlling factor for the Peg3 and Gnas imprinted domains

PubMed Central

Kim, Jeong Do; Hinz, Angela K.; Choo, Jung Ha; Stubbs, Lisa; Kim, Joomyeong

2007-01-01

Imprinting Control Regions (ICRs) often harbor tandem arrays of transcription factor binding sites, as demonstrated by the identification of multiple YY1 binding sites within the ICRs of Peg3, Nespas, and Xist/Tsix domains. In the current study, we have sought to characterize possible roles of YY1 in transcriptional control and epigenetic modification of these imprinted domains. RNA interference-based knockdown experiments in Neuro2A cells resulted in overall transcriptional up-regulation of most of the imprinted genes within the Peg3 domain and also, concomitantly, caused significant loss in the DNA methylation of Peg3-DMR (Differentially Methylated Regions). A similar overall and coordinated expression change was also observed for the imprinted genes of the Gnas domain: up-regulation of Nespas and down-regulation of Nesp and Gnasxl. YY1 knockdown also resulted in changes in the expression levels of Xist and Snrpn. These results support the idea that YY1 plays a major role, as a trans factor, for the control of these imprinted domains. PMID:17067777

12P-conjugated PEG-modified gold nanorods combined with near-infrared laser for tumor targeting and photothermal therapy.

PubMed

Zhan, Tao; Li, Pengfei; Bi, Shan; Dong, Biao; Song, Hongwei; Ren, Hui; Wang, Liping

2012-09-01

Gold nanorods have been reported as potential tumor photothermal therapy in vivo and in vitro. However, development of the safe and efficient tumor-targeting gold nanorods for in vivo localized tumor therapy is still a challenge. In our present study, we synthesized the PEG modified gold nanorods and demonstrated its negligible cytotoxicity in vitro. These nanorods also have been demonstrated to efficiently ablate the different kinds of tumor cells in vitro after exposure to the near-infrared laser. When the PEG modified gold nanorods conjugated with the 12P (sequence: TACHQHVRMVRP), this conjugate showed great tumor-targeting and hyperthermia effects on the human liver cancer cell line HepG2 in vitro when coupled with the near-infrared laser treatment. To determine the potential hyperthermia effect of PEG modified gold nanorods or 12P conjugate on tumor cells in vivo, the mice hepatic cancer cells were used to induce the subcutaneous tumor-bearing model in ICR mice. The significant inhibition effects of near-infrared laser mediated PEG modified gold nanorods or 12P conjugate on the tumor growth were observed. These composite results suggest that the 12P-conjugated PEG modified gold nanorods exhibit great biocompatible, particular tumor-targeting and effective photothermal ablation of tumor cells, which warrant the potential therapeutic value of this conjugate for further application in in vivo localized tumor therapy.

Multifunctional Triblock Nanocarrier (PAMAM-PEG-PLL) for the Efficient Intracellular siRNA Delivery and Gene Silencing

PubMed Central

2011-01-01

A novel triblock poly(amido amine)-poly(ethylene glycol)-poly-l-lysine (PAMAM-PEG-PLL) nanocarrier was designed, synthesized, and evaluated for the delivery of siRNA. The design of the nanocarrier is unique and provides a solution to most of the common problems associated with the delivery and therapeutic applications of siRNA. Every component in the triblock nanocarrier plays a significant role and performs multiple functions: (1) tertiary amine groups in the PAMAM dendrimer work as a proton sponge and play a vital role in the endosomal escape and cytoplasmic delivery of siRNA; (2) PEG, a linker connecting PLL and PAMAM dendrimers renders nuclease stability and protects siRNA in human plasma; (3) PLL provides primary amines to form polyplexes with siRNA through electrostatic interaction and also acts as penetration enhancer; and (4) conjugation to PEG and PAMAM reduced toxicity of PLL and the entire triblock nanocarrier PAMAM-PEG-PLL. The data obtained show that the polyplexes resulted from the conjugation of siRNA, and the proposed nanocarriers were effectively taken up by cancer cells and induced the knock down of the target BCL2 gene. In addition, triblock nanocarrier/siRNA polyplexes showed excellent stability in human plasma. PMID:21322531

Auxin efflux facilitator and auxin dynamism responsible for the gravity-regulated development of peg in cucumber seedlings

NASA Astrophysics Data System (ADS)

Takahashi, Hideyuki; Watanabe, Chiaki; Fujii, Nobuharu; Miyazawa, Yutaka

Cucumber seedlings develop a protuberance, peg, by which seed coats are pulled out just af-ter germination. The peg is usually formed on the lower side of the transition zone between hypocotyl and root of the seedlings grown in a horizontal position. Our previous spaceflight experiment showed that unilateral positioning of a peg in cucumber seedlings occurred due to its suppression on the upper side of the transition zone because seedlings grown in microgravity developed a peg on each side of the transition zone. We also showed that auxin was a major factor responsible for peg development. There was a redistribution of auxin in the gravistimu-lated transition zone, decreasing IAA level on the upper side, and IAA application induced a peg on both lower and upper sides of the transition zone. In addition, peg was released from its suppression in the seedlings treated with inhibitors of auxin efflux. Namely, two pegs devel-oped in the TIBA-treated seedlings even when they were grown in a horizontal position. These results imply that a reduction of auxin level due to its efflux is required for the suppression of peg development on the upper side of the transition zone in a horizontal position. To under-stand molecular mechanism underlying the negative control of morphogenesis by graviresponse in cucumber seedlings, we isolated cDNAs of auxin efflux facilitators, CsPINs, from cucumber and examined the expressions of their proteins, in relation to the redistribution of endogenous auxin and peg development. We isolated six cDNAs of PIN homologues CsPIN1 to CsPIN6 from cucumber. By immunohistochemical study using some of their anti-bodies, we revealed that CsPIN1 was localized in endodermis, vascular tissue and pith around the transition zone of cucumber seedlings. In cucumber seedlings grown in a vertical position with radicles pointing down, CsPIN1 in endodermal cells was mainly localized on the plasma membrane neighboring vascular bundle but not on the plasma membrane

Effects of PEG-induced osmotic stress on growth and dhurrin levels of forage sorghum.

PubMed

O'Donnell, Natalie H; Møller, Birger Lindberg; Neale, Alan D; Hamill, John D; Blomstedt, Cecilia K; Gleadow, Roslyn M

2013-12-01

Sorghum (Sorghum bicolor L. Moench) is a valuable forage crop in regions with low soil moisture. Sorghum may accumulate high concentrations of the cyanogenic glucoside dhurrin when drought stressed resulting in possible cyanide (HCN) intoxication of grazing animals. In addition, high concentrations of nitrate, also potentially toxic to ruminants, may accumulate during or shortly after periods of drought. Little is known about the degree and duration of drought-stress required to induce dhurrin accumulation, or how changes in dhurrin concentration are influenced by plant size or nitrate metabolism. Given that finely regulating soil moisture under controlled conditions is notoriously difficult, we exposed sorghum plants to varying degrees of osmotic stress by growing them for different lengths of time in hydroponic solutions containing polyethylene glycol (PEG). Plants grown in medium containing 20% PEG (-0.5 MPa) for an extended period had significantly higher concentrations of dhurrin in their shoots but lower dhurrin concentrations in their roots. The total amount of dhurrin in the shoots of plants from the various treatments was not significantly different on a per mass basis, although a greater proportion of shoot N was allocated to dhurrin. Following transfer from medium containing 20% PEG to medium lacking PEG, shoot dhurrin concentrations decreased but nitrate concentrations increased to levels potentially toxic to grazing ruminants. This response is likely due to the resumption of plant growth and root activity, increasing the rate of nitrate uptake. Data presented in this article support a role for cyanogenic glucosides in mitigating oxidative stress. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

PEG-PLA diblock copolymer micelle-like nanoparticles as all-trans-retinoic acid carrier: in vitro and in vivo characterizations

NASA Astrophysics Data System (ADS)

Li, Yuan; Qi, Xian Rong; Maitani, Yoshie; Nagai, Tsuneji

2009-02-01

The purpose of this study was to characterize the properties in vitro, i.e. release, degradation, hemolytic potential and anticancer activity, and in vivo disposition of all-trans-retinoic acid (ATRA) in rats after administration of ATRA-loaded micelle-like nanoparticles. The amphiphilic block copolymers consisted of a micellar shell-forming mPEG block and a core-forming PLA block. The mPEG-PLA nanoparticles prepared by an acetone volatilization dialysis procedure were identified as having core-shell structure by 1H NMR spectroscopy. Critical association concentration, drug contents, loading efficiency, particle size and ξ potential were evaluated. The release of ATRA from the nanoparticles and the degradation of PLA were found to be mostly associated with the compositions of the nanoparticles. ATRA release was faster at smaller molecular weight of copolymer and lower drug contents. In vitro, the incorporation of ATRA in mPEG-PLA nanoparticles reduced the hemolytic potential of ATRA. Furthermore, anticancer activity of ATRA against HepG2 cell was increased by encapsulation, which showed an enhancement of tumor treatment of ATRA. In vivo, after intravenous injection to rats, the levels of ATRA in the blood stream and the bioavailability were higher for ATRA-loaded mPEG-PLA nanoparticles than those for ATRA solution. In conclusion, the structure of the mPEG-PLA diblock copolymer could be modulated to fit the demand of in vitro and in vivo characterizations of nanoparticles. The mPEG-PLA nanoparticles' loading ATRA have a promising future for injection administration.

FUSE SPECTROSCOPIC ANALYSIS OF THE SLOWEST SYMBIOTIC NOVA AG PEG DURING QUIESCENCE

NASA Astrophysics Data System (ADS)

Sion, Edward Michael; Godon, Patrick; Katynski, Marcus; Mikolajewska, Joanna

2018-01-01

We present a far ultraviolet spectroscopic analysis of the slowest known symbiotic nova AG Peg (MIII giant + hot white dwarf; P_orb = 818.4 days) which underwent a nova explosion in 1850 followed by a very slow decline that did not end until ~ 1996, marking the beginning of queiscence. Eight years of quiescence ended in June 2015, when AG Peg exhibited a Z And-type outburst with an optical amplitude of ~ 3 magnitudes. We have carried out accretion disk and WD photosphere synthetic spectral modeling of a FUSE spectrum (Froning et al. 2014) obtained on June 5.618, 2003 during the quiescence intervai ~ 12 years before the 2015 outburst. The spectrum is heavily affected by ISM absorption as well as strong broad emission lines. We de-reddened the FUSE fluxes with E(B-V) = 0.10 which is the maximum galactic reddening in the direction of AG Peg and took the distance of 800 pc (Kenyon et al. 1993) but used a range of white dwarf masses, surface temperatures and disk inclination angles. Our analysis also incororates archival HST FOS spectra obtained in 1996 at the onset of quiescence, 147 years after the 1850 nova explosion. The results of our analysis are presented and implications are discussed.This work is supported in part by NASA ADP grant NNX17AF36G to Villanova University.

Dose response of PEG 3350 for the treatment of childhood fecal impaction.

PubMed

Youssef, Nader N; Peters, John M; Henderson, Wendy; Shultz-Peters, Sandra; Lockhart, Danielle K; Di Lorenzo, Carlo

2002-09-01

To investigate the efficacy and safety of polyethylene glycol (PEG) 3350 in the treatment of childhood fecal impaction. This was a prospective, double-blind, parallel, randomized study of 4 doses of PEG 3350; 0.25 g/kg per day, 0.5 g/kg per day, 1 g/kg per day, 1.5 g/kg per day, given for 3 days in children with constipation for >3 months and evidence of fecal impaction. Forty patients completed the study (27 boys, median age 7.5, range 3.3-13.1 years). Disimpaction occurred in 75% of children, with a significant difference between the two higher doses and the lower doses (95% vs 55%, P <.005). All groups had an increased number of bowel movements during the 5-day study versus baseline, respectively: 6.5 versus 1.1 (P <.005), 8.0 versus 1.3 (P <.005), 10.9 versus 1.7 (P <.005), and 12.3 versus 1.4 (P <.005). Adverse effects included nausea (5%), vomiting (5%), bloating (18%), cramping (5%), and diarrhea (13%). Diarrhea and bloating were more prevalent (P <.02) in the higher-dose than in the lower-dose group. No clinically significant changes in electrolytes were noted. The 3-day administration of PEG 3350 is safe and effective in the treatment of childhood fecal impaction at doses of 1 and 1.5 g/kg per day.

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

PubMed

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

2016-12-01

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

Codelivery of SH-aspirin and curcumin by mPEG-PLGA nanoparticles enhanced antitumor activity by inducing mitochondrial apoptosis.

PubMed

Zhou, Lin; Duan, Xingmei; Zeng, Shi; Men, Ke; Zhang, Xueyan; Yang, Li; Li, Xiang

2015-01-01

Natural product curcumin (Cur) and H2S-releasing prodrug SH-aspirin (SH-ASA) are potential anticancer agents with diverse mechanisms, but their clinical application prospects are restricted by hydrophobicity and limited efficiency. In this work, we coencapsulated SH-ASA and Cur into methoxy poly(ethylene glycol)-poly (lactide-coglycolide) (mPEG-PLGA) nanoparticles through a modified oil-in-water single-emulsion solvent evaporation process. The prepared SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles had a mean particle size of 122.3±6.8 nm and were monodispersed (polydispersity index =0.179±0.016) in water, with high drug-loading capacity and stability. Intriguingly, by treating with SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles, obvious synergistic anticancer effects on ES-2 and SKOV3 human ovarian carcinoma cells were observed in vitro, and activation of the mitochondrial apoptosis pathway was indicated. Our results demonstrated that SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles could have potential clinical advantages for the treatment of ovarian cancer.

Codelivery of SH-aspirin and curcumin by mPEG-PLGA nanoparticles enhanced antitumor activity by inducing mitochondrial apoptosis

PubMed Central

Zhou, Lin; Duan, Xingmei; Zeng, Shi; Men, Ke; Zhang, Xueyan; Yang, Li; Li, Xiang

2015-01-01

Natural product curcumin (Cur) and H2S-releasing prodrug SH-aspirin (SH-ASA) are potential anticancer agents with diverse mechanisms, but their clinical application prospects are restricted by hydrophobicity and limited efficiency. In this work, we coencapsulated SH-ASA and Cur into methoxy poly(ethylene glycol)-poly (lactide-coglycolide) (mPEG-PLGA) nanoparticles through a modified oil-in-water single-emulsion solvent evaporation process. The prepared SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles had a mean particle size of 122.3±6.8 nm and were monodispersed (polydispersity index =0.179±0.016) in water, with high drug-loading capacity and stability. Intriguingly, by treating with SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles, obvious synergistic anticancer effects on ES-2 and SKOV3 human ovarian carcinoma cells were observed in vitro, and activation of the mitochondrial apoptosis pathway was indicated. Our results demonstrated that SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles could have potential clinical advantages for the treatment of ovarian cancer. PMID:26316750

In Vivo Anticancer Efficacy and Toxicity Studies of a Novel Polymer Conjugate N-Acetyl Glucosamine (NAG)-PEG-Doxorubicin for Targeted Cancer Therapy.

PubMed

Pawar, Smita; Mahajan, Ketan; Vavia, Pradeep

2017-11-01

A novel polymer-drug conjugate, polyethylene glycol-N-(acetyl)-glucosamine-doxorubicin (PEG-NAG-DOX) was evaluated in this study for its in vivo potential for treatment of tumours demonstrating improved efficacy and reduced toxicity. The proposed polymer-drug conjugate comprised of polyethylene glycol-maleimide (mPEG-MAL, 30000 Da) as a carrier, doxorubicin (DOX) as an anticancer drug and N-acetyl glucosamine (NAG) as a targeting moiety as well as penetration enhancer. Doxorubicin has a potent and promising anticancer activity; however, severe cardiotoxicity limits its application in cancer treatment. By modifying DOX in PEG-NAG-DOX prodrug conjugate, we aimed to eliminate this limitation. In vivo anticancer efficacy of the conjugate was evaluated using BDF mice-induced skin melanoma model by i.v. administration of DOX conjugates. Anticancer efficacy studies were done by comparing tumour volume, body weight, organ index and percent survival rate of the animals. Tumour suppression achieved by PEG-NAG-DOX at the cumulative dose of 7.5 mg/kg was two-fold better than that achieved by DOX solution. Also, the survival rate for PEG-NAG-DOX conjugate was >70% as compared to <50% survival rate for DOX solution. In addition, toxicity studies and histopathological studies revealed that while maintaining its cytotoxicity towards tumour cells, PEG-NAG-DOX conjugate showed no toxicities to major organs. Therefore, PEG-NAG-DOX conjugate can be suggested as a desirable candidate for targeted cancer therapy.

The storage capacity of cocoa seeds (Theobroma cacao L.) through giving Polyethylene Glycol (PEG) in the various of storage container

NASA Astrophysics Data System (ADS)

Lahay, R. R.; Misrun, S.; Sipayung, R.

2018-02-01

Cocoa is plant which it’s seed character is recalcitrant. Giving PEG and using various of storage containers was hoped to increase storage capacity of cocoa seeds as long as period of saving. The reseach was aimed to identify the storage capacity of cocoa seeds through giving PEG in the various of storage containers. Research took place in Hataram Jawa II, Kabupaten Simalungun, Propinsi Sumatera Utara, Indonesia. The method of this research is spit-split plot design with 3 replication. Storage period was put on main plot which was consisted of 4 level, PEG concentration was put on sub plot, consisted of 4 level and storage container was put on the sub sub plot consisted of 3 types. The results showed that until 4 days at storage with 45 % PEG concentration at all storage container, percentage of seed germination at storage can be decreased to be 2.90 %, and can be defensed until 16 days with 45 % PEG concentration at perforated plastic storage container. Percentage of molded seeds and seed moisture content were increased with added period of storage but seed moisture content was increased until 12 days at storage and was decreased at 16 days in storage.

Imaging experimental intraabdominal abscesses with 99mTc-PEG liposomes and 99mTc-HYNIC IgG.

PubMed Central

Dams, E T; Reijnen, M M; Oyen, W J; Boerman, O C; Laverman, P; Storm, G; van der Meer, J W; Corstens, F H; van Goor, H

1999-01-01

OBJECTIVE: To evaluate the accuracy of technetium-99m-labeled polyethylene glycol-coated liposomes (99mTc-PEG liposomes) and technetium-99m-labeled nonspecific human immunoglobulin G (99mTc-HYNIC IgG) for the scintigraphic detection of experimental intraabdominal abscesses in comparison with that of a standard agent, gallium-67 citrate. BACKGROUND: Scintigraphic imaging techniques can be very useful for the rapid and accurate localization of intraabdominal abscesses. Two newly developed radiolabeled agents, 99mTc-PEG liposomes and 99mTc-HYNIC IgG, have shown to be excellent agents for imaging experimental focal infection, but have not yet been studied in the detection of abdominal abscesses. METHODS: Intraabdominal abscesses were induced in 42 rats using the cecal ligation and puncture technique. Seven days later, randomized groups of rats received 99mTc-PEG liposomes, 99mTc-HYNIC IgG, or 67Ga citrate intravenously. The rats were imaged up to 24 hours after the injection. The biodistribution of the radiolabel was determined by counting dissected tissues ex vivo. Macroscopic intraabdominal abnormalities and focal uptake on the images were independently scored on a semiquantitative scale. RESULTS: 99mTc-PEG liposomes provided the earliest scintigraphic visualization of the abscess (as soon as 2 hours after the injection vs. 4 hours for the other two agents). Liposomes, IgG, and gallium all showed similarly high absolute uptake in the abscess. Focal uptake of liposomes and gallium correlated best with the extent of the macroscopic abnormalities. CONCLUSIONS: 99mTc-PEG liposomes and 99mTc-HYNIC IgG performed at least as well as the standard agent, 67Ga citrate, in the detection of experimental intraabdominal abscesses, with obvious advantages such as lower radiation exposure and more favorable physical properties. Of the two technetium agents, the liposomes seemed to be superior, providing the earliest diagnostic image and the best correlation with the inflammatory

Reduction of Non-Specific Protein Adsorption Using Poly(ethylene) Glycol (PEG) Modified Polyacrylate Hydrogels In Immunoassays for Staphylococcal Enterotoxin B Detection

PubMed Central

Charles, Paul T.; Stubbs, Veronte R.; Soto, Carissa M.; Martin, Brett D.; White, Brandy J.; Taitt, Chris R.

2009-01-01

Three PEG molecules (PEG-methacrylate, -diacrylate and -dimethacrylate) were incorporated into galactose-based polyacrylate hydrogels and their relative abilities to reduce non-specific protein adsorption in immunoassays were determined. Highly crosslinked hydrogels containing amine-terminated functionalities were formed and used to covalently attach antibodies specific for staphylococcal enterotoxin B (SEB). Patterned arrays of immobilized antibodies in the PEG-modified hydrogels were created with a PDMS template containing micro-channels for use in sandwich immunoassays to detect SEB. Different concentrations of the toxin were applied to the hydrogel arrays, followed with a Cy3-labeled tracer antibody specific for the two toxins. Fluorescence laser scanning confocal microscopy of the tracer molecules provided both qualitative and quantitative measurements on the detection sensitivity and the reduction in non-specific binding as a result of PEG incorporation. Results showed the PEG-modified hydrogel significantly reduced non-specific protein binding with a detection limit for SEB of 1 ng/mL. Fluorescence signals showed a 10-fold decrease in the non-specific binding and a 6-fold increase in specific binding of SEB. PMID:22389622

Modelo de accesibilidad de conceptos matematicos aplicados en el curso de Astronomia Descriptiva para estudiantes con impedimentos visuales en la UPR

NASA Astrophysics Data System (ADS)

Isidro Villamizar, Gloria Maria

Este estudio utiliza metodologia de investigacion cualitativa, con el proposito de describir, analizar y evaluar los procesos de diseno y desarrollo de un modelo de accesibilidad que consiste en estrategias de ensenanza de las matematicas para estudiantes con impedimentos visuales matriculados en el curso de Astronomia Descriptiva en la UPR. Se utilizaron las siguientes estrategias para recopilar la informacion, 1) reflexiones de la investigadora en el proceso de diseno y desarrollo de las lecciones adaptadas, que se registraron en un diario reflexivo. 2) entrevista semiestructurada luego de haber trabajado las lecciones de aprendizaje adaptadas con los participantes. 3) observaciones y notas de la investigadora del trabajo de los participantes. Para obtener la informacion de los participantes se obtuvo los permisos institucionales necesarios; se seleccionaron los participantes y se validaron los instrumentos; se realizo el desarrollo de las lecciones adaptadas con los participantes; y finalmente, se analizo la informacion obtenida. El diseno de las lecciones de aprendizaje adaptadas se hizo siguiendo las recomendaciones curriculares de los temas de matematicas aplicados en el curso de Astronomia Descriptiva realizado por la investigadora durante su semestre de internado. El testimonio de las voces de los participantes se obtuvo del proceso de desarrollo de las lecciones de aprendizaje adaptadas de temas seleccionados de conceptos matematicos requeridos en el curso de Astronomia Descriptiva y de la entrevista semiestructurada con los participantes, luego de haber trabajado las lecciones de aprendizaje. Para el desarrollo de las lecciones de aprendizaje, se utilizaron materiales tactiles adaptados, materiales tactiles disenados y materiales disponibles comercialmente. Los textos de las lecciones se imprimieron en tinta y en Braille. Se exhorta a disenar y desarrollar estrategias de ensenanza accesibles, considerando como recursos para evaluar su efectividad a

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

NASA Astrophysics Data System (ADS)

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

2016-06-01

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

Comparison of effectiveness between cork-screw and peg-screw electrodes for transcranial motor evoked potential monitoring using the finite element method.

PubMed

Tomio, Ryosuke; Akiyama, Takenori; Ohira, Takayuki; Yoshida, Kazunari