Effects of poly(ethylene glycol) (PEG) concentration on the permeability of PEG-grafted liposomes

Poly(ethylene glycol)-grafted liposomes (PEG-liposomes) were prepared from dipalmitoylphosphatidylcholine (DPPC) with various amounts of distearoyl-N-monomethoxy poly(ethylene glycol)-succinyl-phosphatidylethanolamines (DSPE-PEG) with PEG molecular weights of 1000, 2000, 3000 and 5000. The effects of DSPE-PEG concentration on the permeability of PEG-liposomes were investigated using carboxyfluorescein (CF). In the gel state, the CF leakage from PEG-liposomes was decreased with increasing mole fractions of DSPE-PEG for all PEG molecular weights. In the liquid-crystalline state, the CF leakage from PEG-liposomes containing DSPE-PEG1000 gradually increased with increasing mole fractions of DSPE-PEG, while that of PEG-liposomes whose molecular weight in PEG units was above 2000 rapidly decreased by the addition of DSPE-PEG. Furthermore, no effect of PEG molecular weight on CF leakage was observed. The relationship between the fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) (or 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH)) and the mole fraction of DSPE-PEG for PEG-liposomes was also investigated. No significant changes in fluorescence polarization of DPH for liposomal bilayer membranes was observed in the gel and liquid-crystalline states due to the addition of DSPE-PEG, while that of TMA-DPH was decreased compared with that of liposomes without DSPE-PEG in both states.     

Graft copolymers of poly(ethylene glycol) (PEG) and chitosan

Graft copolymers of poly(ethylene glycol) (PEG) on a chitosan backbone (PEG-g-chitosan) have been synthesized and their aqueous solution properties were investigated. At pH 6.5 the graft copolymers are 100% soluble, while chitosan phase separates from solution at those conditions. These interesting graft copolymers may be especially suitable as carriers for delivery of anionic drugs, such as proteins, glycosaminoglycans, and DNA plasmids or oligonucleotides.     

Interactions between poly(2-ethylacrylic acid) and lipid bilayer membranes: effects of cholesterol and grafted poly(ethylene glycol)

The exchange of the protonatable polymer, poly(2-ethylacrylic acid) (PEAA), has been studied with vesicle membranes containing cholesterol from 0 to 60 mol% or PEG2000-lipid (5 mol%). The release of an entrapped dye from 100 nm extruded liposomes was used as an assay for membrane perturbation by the polymer as a function of pH. The inclusion of cholesterol was found to reduce the pH at which the polymer caused release of the dye from the lipid vesicles, and the degree of polymer protonation (i.e., degree of hydrophobicity) correlated well with the increase in elastic expansion modulus of the vesicle bilayer. The results are discussed in terms of a balance between polymer solubility and membrane expansion. With respect to the PEG barrier, the presence of 5 mol% PEG2000, which represents full surface coverage, did not prevent PEAA from inducing contents release, demonstrating that highly hydrated polymeric layers are not effective barriers for other water soluble polymers, and may point to some association between the two polymers.     

Effects of poly(ethylene glycol) branch chain linkage mode on polycarboxylate superplasticizer performance

Polycarboxylate superplasticizers (PCs) with ether linkages and ester linkages between the main chains and the poly(ethylene glycol) (PEG) branch chains were synthesized, respectively. The effects of the PCs molecule linkage mode on the performance of concrete paste were investigated using the slump loss test and thermogravimetric analysis and analyzing fluidity, absorption, and setting time. Results showed that the linkage between main chains and PEG branch chains in PCs molecules had an important influence on the performance of cement paste and concrete prepared from them. PCs with ester linkages can endow the cement paste with higher fluidity and higher water‐reduction ratio resulting from the higher absorption amount on the cement particles. This is related with the alternating distribution of the carboxyl groups and branch chains of PEG when different macromonomers are involved in the preparation of PCs. PCs containing ester linkages are more vulnerable than PCs with ether linkages in an alkali environment, leading to quicker slump loss and shorter setting times. In contrast, PCs with ether linkages had excellent fluidity and slump flow stability. A slightly different ettringite hydration product was observed during the early period of the hydration of cement paste that employed these two PCs. Copyright © 2012 John Wiley & Sons, Ltd.     

Surface modification of polyethersulfone membranes by blending triblock copolymers of methoxyl poly(ethylene glycol)-polyurethane-methoxyl poly(ethylene glycol)

The surface of polyethersulfone (PES) membrane was modified by blending triblock copolymers of methoxyl poly(ethylene glycol)-polyurethane-methoxyl poly(ethylene glycol) (mPEG-PU-mPEG), which were synthesized through solution polymerization with mPEG Mns of 500 and 2000, respectively. The PES and PES/mPEG-PU-mPEG blended membranes were prepared through spin coating coupled with liquid-liquid phase separation. FTIR and (1)H NMR analysis confirmed that the triblock copolymers were successfully synthesized. The functional groups and morphologies of the membranes were studied by ATR-FTIR and SEM, respectively. It was found that the triblock copolymers were blended into PES membranes successfully, and the morphologies of the blended membranes were somewhat different from PES membrane. The water contact angles and platelet adhesion were decreased after blending mPEG-PU-mPEG into PES membranes. Meanwhile, the activated partial thromboplastin time (APTT) for the blended membranes increased. The anti-protein-fouling property and permeation property of the blended membranes improved obviously. SEM observation and 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay proved the surfaces of the blended membranes promoted human hepatocytes adhesion and proliferation better than PES membrane.     

Self-threading of a poly(ethylene glycol) chain in a cyclodextrin-ring: control of the exchange dynamics by chain length

Poly(ethylene glycol) (PEG)-substituted cyclodextrins (CDs) with different chain lengths have been synthesized. PEG-substituted CDs formed self-threading complexes in aqueous solutions, and the conformational exchange dynamics between self-threading and dethreading could be regulated by its chain length.     

Composite proton-conducting membranes based on poly(ethylene glycol vinyl glycidyl ether)

Composite proton-conducting membranes in the form of interpolymer films are prepared in an aqueous medium from sulfo-acid-modified poly(ethylene glycol vinyl glycidyl ether) and poly(vinyl alcohol). The initial poly(hydroxysulfo acid) is synthesized through the radical polymerization of ethylene glycol vinyl glycidyl ether followed by modification with sodium sulfite via epoxy groups and treatment with a cationite in the H form. The proton-conducting membranes feature improved thermal stability (200–250°C), a breaking strength of 1.0–8.9 MPa, elasticity (a relative elongation at break of 1.0–8.2%), chemical resistance, and specific proton conductivity attaining 10^?1 S/cm after doping with orthophosphoric acid.     

Adsorption of poly(ethylene glycol) s on mercury/aqueous solution interface 2. Influence of the chain length

The adsorption on a mercury/aqueous solution interface of poly(ethylene glycol)s (PEGs) with molecular weights from 200 to 20 000 was studied by a.c. voltammetry in order to understand better the adsorption of linear components of fulvic acids on hydrophobic particles in natural waters, and the influence of their adsorption on voltammetric signals. As a general trend it was noted that the equilibrium adsorption constant increases with the molecular weight while the adsorption rate decreases. The values of the maximum surface concentration F. suggest a flat configuration for adsorbed molecules for all PEGs studied.     

Novel tricomponent membranes containing poly(ethylene glycol)/poly(pentamethylcyclopentasiloxane)/poly(dimethylsiloxane) domains

The synthesis and characterization of novel tricomponent networks consisting of well‐defined poly(ethylene glycol) (PEG) and poly(dimethylsiloxane) (PDMS) strands crosslinked and reinforced by poly(pentamethylcyclopentasiloxane) (PD₅) domains are described. Network synthesis occurred by dissolving α,ω‐diallyl PEG and α,ω‐divinyl PDMS prepolymers in a common solvent (toluene), introducing a stoichiometric excess of pentamethylcyclopentasiloxane (D₅H) to the charge, inducing the cohydrosilation of the prepolymers by Karstedt's catalyst and completing network formation by the addition of water. Water in the presence of the Pt‐based catalyst oxidizes the SiH groups of D₅H to SiOH functions that immediately polycondense and bring about crosslinking. The progress of cohydrosilation and polycondensation was followed by monitoring the disappearance of the SiH and SiOH functions by Fourier transform infrared spectroscopy. Because cohydrosilation and polycondensation are essentially quantitative, overall network composition can be controlled by calculating the stoichiometry of the three network constituents. The very low quantities of extractable (sol) fractions corroborate efficient crosslinking. The networks swell in both water and hexanes. Differential scanning calorimetry showed three thermal transitions assigned, respectively, to PEG (melting temperature: 46–60 °C depending on composition), PDMS [glass‐transition temperature (T_g) = ～?121 °C], and PD₅ (T_g = ～?159 °C) and indicated a phase‐separated tricomponent nanoarchitecture. The low T_g of the PD₅ phase is unprecedented. The strength and elongation of PEG/PD₅/PDMS networks can be controlled by overall network composition. The synthesis of networks exhibiting sufficient mechanical properties (tensile stress: 2–5 MPa, elongation: 100–800%) for various possible applications has been demonstrated. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 3093–3102, 2002     

A novel cell-impermeable fluorescent zinc sensor containing poly(ethylene glycol) chain

A novel cell-impermeable zinc sensor was synthesized by incorporating poly（ethylene glycol）（PEG） to N-（8-quinolyl）-p-aminobenzenesulfonamide （HQAS） group.The polymeric zinc sensor combines both valuable features of HQAS and PEG.The HQAS of the sensor has the similar functions to TSQ,and exhibits a good fluorescence response to Zn²⁺ but poor fluorescence responses to other metal ions.The PEG chain can prevent the sensor to permeate healthy cell membrane.The stained experiments with the yeast cells as model showed that the sensor cannot stain the healthy yeast cells,but only the damaged or died yeast cells. These results indicated the novel zinc probe was a typical cell-impermeable zinc sensor.     

Segmented block copolymers of poly(ethylene glycol) and poly(ethylene terephthalate)

A new series of segmented copolymers were synthesized from poly(ethylene terephthalate) (PET) oligomers and poly(ethylene glycol) (PEG) by a two‐step solution polymerization reaction. PET oligomers were obtained by glycolysis depolymerization. Structural features were defined by infrared and nuclear magnetic resonance (NMR) spectroscopy. The copolymer composition was calculated via ¹H NMR spectroscopy. The content of soft PEG segments was higher than that of hard PET segments. A single glass‐transition temperature was detected for all the synthesized segmented copolymers. This observation was found to be independent of the initial PET‐to‐PEG molar ratio. The molar masses of the copolymers were determined by gel permeation chromatography (GPC). © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4448–4457, 2004     

Micro- and nanopatterned star poly(ethylene glycol) (PEG) materials prepared by UV-based imprint lithography

A UV-based imprint lithography method is used for the direct surface structuring of hydrogel-based biomaterials, which are prepared from a family of tailor-made star poly(ethylene glycol) formulations. Bulk star poly(ethylene glycol) (PEG) hydrogels are fabricated by cross-linking acrylate-functionalized star PEG macromolecules. Cross-linking is achieved by radical reactions initiated by UV irradiation. This UV-curable star PEG formulation allows templating of mold structures to yield a stable, stand-alone, elastomeric replica of the mold. In particular, when a secondary, soft mold is used that consists of a perfluorinated elastomer with inherent excellent release properties, nanometer-sized features (down to 100 nm) can be imprinted without specialized equipment. The applied UV-based imprint lithography is a fast and simple technique to employ for the direct topographic structuring of bulk PEG-based biomaterials. The UV-based imprinting into the star PEG prepolymer by means of a perfluorinated, soft mold can be carried out on the bench top, while nanoscale resolution is demonstrated.     

Formation of nanoporous poly(aryl amide ether) (PAAE) films by selective removal of poly(ethylene glycol) (PEG) from PEG/PAAE composite films

Poly(aryl amide ether) (PAAE) thin films with nanometer-sized pores have been prepared in two steps: (1) solution casting of partially miscible poly(ethylene glycol) (PEG)/PAAE blends from one of their common solvents, dimethyl sulfoxide (DMSO), results in formation of PEG/PAAE nanocomposite films; (2) selective removal of PEG component by water washing yields nanosized, porous PAAE films. The pores have been found to have a small size variation and cover the whole surface homogeneously. With an increase in PEG contents, the sizes of the pores increase but the size distributions do not have much changes. This has been ascribed to formation of small PEG domains in PEG/PAAE composite films, which is facilitated by the strong interactions, mostly hydrogen bonds, between PEG and PAAE macromolecular chains.     

Nonisothermal crystallization behavior of the poly(ethylene glycol) block in poly(L‐lactide)–poly(ethylene glycol) diblock copolymers: Effect of the poly(L‐lactide) block length

The confined crystallization behavior, melting behavior, and nonisothermal crystallization kinetics of the poly(ethylene glycol) block (PEG) in poly(L ‐lactide)–poly(ethylene glycol) (PLLA–PEG) diblock copolymers were investigated with wide‐angle X‐ray diffraction and differential scanning calorimetry. The analysis showed that the nonisothermal crystallization behavior changed from fitting the Ozawa equation and the Avrami equation modified by Jeziorny to deviating from them with the molecular weight of the poly(L ‐lactide) (PLLA) block increasing. This resulted from the gradual strengthening of the confined effect, which was imposed by the crystallization of the PLLA block. The nucleation mechanism of the PEG block of PLLA15000–PEG5000 at a larger degree of supercooling was different from that of PLLA2500–PEG5000, PLLA5000–PEG5000, and PEG5000 (the numbers after PEG and PLLA denote the molecular weights of the PEG and PLLA blocks, respectively). They were homogeneous nucleation and heterogeneous nucleation, respectively. The PLLA block bonded chemically with the PEG block and increased the crystallization activation energy, but it provided nucleating sites for the crystallization of the PEG block, and the crystallization rate rose when it was heterogeneous nucleation. The number of melting peaks was three and one for the PEG homopolymer and the PEG block of the diblock copolymers, respectively. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 3215–3226, 2006     

Preparation and Characterization of Chitosan Composite Membranes Crosslinked by Carboxyl-capped Poly（ethylene glycol）

In this study a series of chemically crosslinked chitosan/poly（ethylene glycol） （CS/PEG） composite membranes were prepared with PEG as a crosslinking reagent other than an additional blend. First, carboxyl-eapped poly（ethylene glycol） （HOOC-PEG-COOH） was synthesized. Dense CS/PEG composite membranes were then prepared by casting/evaporation of CS and HOOC-PEG-COOH mixture in acetic acid solution. Chitosan was chemically crosslinked due to the amidation between the carboxyl in HOOC-PEG-COOH and the amino in chitosan under heating, as confirmed by FTIR analysis. The hydrophilicity, water-resistance and mechanical properties of pure and crosslinked chitosan membranes were characterized, respectively. The results of water contact angle and water absorption showed that the hydrophilicity of chitosan membranes could be significantly improved, while no significant difference of weight loss between pure chitosan membranes and crosslinked ones was detected, indicating that composite membranes with amidation crosslinking possess excellent water resistanance ability. Moreover, the tensile strength of chitosan membranes could be significantly enhanced with the addition of certain amount of HOOC-PEG-COOH crosslinker, while the elongation at break didn＇t degrade at the same time. Additionally, the results of swelling behaviors in water at different pH suggested that the composite membranes were pH sensitive.     

Synthesis of poly(ethylene glycol) (PEG)-grafted colloidal silica particles with improved stability in aqueous solvents

The known grafting procedures of colloidal silica particles with poly(ethylene glycol) (PEG) lead to grafting layers that detach from the silica surface and dissolve in water within a few days. We present a new grafting procedure of PEG onto silica with a significant improvement of the stability of the grafting layers in aqueous solvents. Moreover, the procedure avoids any dry states or other circumstances leading to strong aggregation of the particles. To achieve the improved water stability, St?ber silica particles are first pre-coated with a silane coupling agent (3-aminopropyl)triethoxysilane (APS) to incorporate active amine groups. The water solubility of the pre-coating layer was minimized using a combination of APS with bis-(trimethoxysilylpropyl)amine (BTMOSPA) or bis-(triethoxysilyl)ethane (BTEOSE). These pre-coated particles were then reacted with N-succinimidyl ester of mono-methoxy poly(ethylene glycol) carboxylic acid to form PEG-grafted silica particles. The particles form stable dispersions in aqueous solutions as well as several organic solvents.     

New approach on the development of plasticized polylactide (PLA): Grafting of poly(ethylene glycol) (PEG) via reactive extrusion

In this work, new ways of plasticizing polylactide (PLA) with low molecular poly(ethylene glycol) (PEG) were developed to improve the ductility of PLA while maintaining the plasticizer content at maximum 20 wt.% PLA. To this end, a reactive blending of anhydride-grafted PLA (MAG-PLA) copolymer with PEG, with chains terminated with hydroxyl groups, was performed. During the melt-processing, a fraction of PEG was grafted into the anhydride-functionalized PLA chains. The role of the grafted fraction was to improve the compatibility between PLA and PEG. Reactive extrusion and melt-blending of neat and modified PLA with PEG did not induce any dramatic drop of PLA molecular weight. The in situ reactive grafting of PEG into the modified PLA in PLA/PEG blends showed a clear effect on the thermal properties of PLA. It was demonstrated by DSC that the mobility gained by PLA chains in the plasticized blends yielded crystallization. The grafting of a fraction of PEG into PLA did not affect this process. However, DSC results obtained after the second heating showed an interesting effect on the T_g when 20 wt.% PEG were melt blended with neat PLA or 10 wt.% MAG-PLA. In the latter case, the T_g displayed by the reactive blend was shifted to even lower temperatures at around 14 °C, while the T_g of neat PLA and PLA blended with 20 wt.% PEG was around 60 and 23 °C, respectively. Regarding viscoelastic and viscoplastic properties, the presence of MAG-PLA does not significantly influence the behavior of plasticized PLA. Indeed, with or without MAG-PLA, elastic modulus and yield stress decrease, while ultimate strain increases with the addition of PEG into PLA.     

Exploring the scope of poly(ethylene glycol) (PEG) as a soluble polymer matrix for the Stille cross-coupling reaction

The optimization and efficient parallel synthesis and purification of a library of biaryl, heterobiaryl, and styryl derivatives, via the first reported poly(ethylene glycol)-supported palladium-catalyzed Stille procedure, are described. Preliminary investigations into the reaction between monomethoxy poly(ethylene glycol)5000-supported iodide 1a with tributylphenyltin 2 revealed that the optimal "liquid-phase" conditions employ PdCl2(PPh3)2 (0.1 equiv) catalysis with LiCl (10 equiv) in DMF at 80 degrees C for either 48 h (at 20 mM concentration of 1a) or 24 h (at 10 mM concentration of 1a). The soluble polymer-supported reaction is superior to its solution-phase counterpart because the tributyltin side products and excess reagents are easily separated from the product intermediate 3a by precipitation of 3a into diethyl ether followed by recovery of the polymer by filtration in > 99%. In addition, the homocoupled byproduct 6 is also removed during this precipitation step. Under these conditions the transesterified biaryl adduct 4a can be isolated in 97-98% yield. The scope of this reaction was probed in a parallel format with the PEG-supported electrophiles 1a-b and a range of tributyl stannanes 2 and 7-13 under the optimized conditions vide supra. Subsequent cleavage of the polymer-supported adducts, by transesterification, and short column chromatography yielded a library of substituted methyl benzoates 4a-b and 14a-b to 20a-b in high yield (69-99%) and purity (> 95%).     

Effect of poly(ethylene glycol) (PEG) spacers on the conformational properties of small peptides: a molecular dynamics study

Poly(ethylene glycol) (PEG) is used as an inert spacer in a wide range of biotechnological applications such as to display peptides and proteins on surfaces for diagnostic purposes. In such applications it is critical that the peptide is accessible to solvent and that the PEG does not affect the conformational properties of the peptide to which it is attached. Using molecular dynamics (MD) simulation techniques, we have investigated the influence of a commonly used PEG spacer on the conformation properties of a series of five peptides with differing physical-chemical properties (YGSLPQ, VFVVFV, GSGGSG, EEGEEG, and KKGKKG). The conformational properties of the peptides were compared (a) free in solution, (b) attached to a PEG-11 spacer in solution, and (c) constrained to a two-dimensional lattice via a (PEG-11)(3) spacer, mimicking a peptide displayed on a surface as used in microarray techniques. The simulations suggest that the PEG spacer has little effect on the conformational properties of small neutral peptides but has a significant effect on the conformational properties of small highly charged peptides. When constrained to a two-dimensional surface at peptide densities similar to those used experimentally, it was found that the peptides, in particular the polar and nonpolar peptides, aggregated strongly. The peptides also partitioned into the PEG layer. Potentially, this means that at high packing densities only a small fraction of the peptide attached to the surface would in fact be accessible to a potential interaction partner.     

Novel Biodegradable Block Copolymers of Poly(ethylene glycol) (PEG) and Cationic Polycarbonate: Effects of PEG Configuration on Gene Delivery

A novel amine‐functionalized polycarbonate was synthesized and its excellent gene transfection ability in vitro is demonstrated. In the framework of adapting the cationic polycarbonate for in vivo gene delivery applications, here the design and synthesis of biodegradable block copolymers of poly(ethylene glycol) (PEG) and amine‐functionalized polycarbonate with a well‐defined molecular architecture and molecular weight is achieved by metal‐free organocatalytic ring‐opening polymerization. Copolymers in triblock cationic polycarbonate‐block‐PEG‐block‐cationic polycarbonate and diblock PEG‐block‐cationic polycarbonate configurations, in comparison with a non‐PEGylated cationic polycarbonate control, are investigated for their influence on key aspects of gene delivery. Among the polymers with similar molecular weights and N content, the triblock copolymer exhibit more favorable physicochemical (i.e., DNA binding, size, zeta‐potential, and in vitro stability) and biological (i.e., cellular uptake and luciferase reporter gene expression) properties. Importantly, the various cationic polycarbonate/DNA complexes are biocompatible, inducing minimal cytotoxicities and hemolysis. These results suggest that the triblock copolymer is a more useful architecture in future cationic polymer designs for successful systemic therapeutic applications.