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.     

Self-assembly of poly(ethylene glycol)-based block copolymers for biomedical applications

Nanostructure fabrication from block copolymers is discussed in this review paper. Particularly, novel approaches for the construction of functionalized poly(ethylene glycol) (PEG) layers on surfaces were focused to attain the specific adsorption of a target protein through PEG-conjugated ligands with a minimal non-specific adsorption of other proteins. Furthermore, surface organization of block copolymer micelles with cross-linking cores was described from the standpoint of preparation of a new functional surface-coating with a unique macromolecular architecture. The micelle-attached surface and the thin hydrogel layer made by layered micelles exhibited non-fouling properties and worked as a reservoir for hydrophobic reagents. These PEG-functionalized surface in brush form or in micelle form can be used in diverse fields of medicine and biology to construct high-performance medical devices including scaffolds for tissue engineering and matrices for drug delivery systems.     

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.     

ChemMatrix, a poly(ethylene glycol)-based support for the solid-phase synthesis of complex peptides

CM (ChemMatrix) resin is a new, totally poly(ethylene glycol) (PEG)-based resin, made exclusively from primary ether bonds and, therefore, highly chemically stable. It exhibits good loading and is user-friendly because of its free-flowing form upon drying. It performs excellently for the preparation of hydrophobic, highly structured, and poly-Arg peptides, as compared to polystyrene (PS) resins. In the most striking example, stepwise solid-phase assembly of the highly complex beta-amyloid (1-42) peptide resulted in a crude material of 91% purity. In contrast, literature procedures using PS or PEG-PS-based resins for this peptide required convergent approaches, additional time-consuming steps, or both. In addition to the difficulties of its synthesis, characterization of the beta-amyloid (1-42) peptide as a monomer is also a challenge, and methods for characterization by HPLC and MALDI-TOF have also been developed.     

Antifriction properties of fluorine-containing poly(ethylene glycol) esters

Equilibrium mixtures of fluorine-containing mono- and diesters based on poly(ethylene glycol) (M = 1000) were synthesized. The effect of these compounds on antifriction properties of industrial oil was studied.     

Rheological properties of poly(ethylene glycol) solutions and gels

By the interaction of a water–glycol solution of poly(ethylene glycol) (PEG) with calcium chloride dihydrate, a gel was produced. It was determined that, below a certain shear rate, this gel is a Newtonian fluid; however, above a certain shear rate, which depends on the gel viscosity, the properties of this gel are anomalous: the gel flow instantaneously completely stops. The viscosity of the gels was found to exponentially increase with increasing concentration of the cross-linking metal at constant PEG concentration. The density of the gels linearly increases with increasing concentration of the cross-linking metal at constant PEG concentration.     

Green polymer chemistry: Telechelic poly(ethylene glycol)s via enzymatic catalysis

This article reports our discovery that poly(ethylene glycol) (PEG) can quantitatively be functionalized by transesterification using Candida antarctica lipase B (Novozyme 435) as the catalyst. α‐ω telechelic PEG‐methacrylates and PEG‐acetates were successfully prepared using commercially available PEGs with both narrow and broad molecular weight distribution. ¹H and ¹³C NMR together with MALDI‐TOF mass spectroscopy verified the expected structures. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 3024–3028, 2008     

Synthesis of poly(ethylene glycol)-functionalized hydroxyapatite organic colloid intended for nanocomposites

Traditional modifications to hydroxyapatite(HA) nanoparticles usually occurred after HA synthesis and thus are insufficient to avoid particle agglomeration.In this study,a new heterofunctional poly(ethylene glycol)(PEG) with phosphoric acid and carboxyl end groups,i.e.,α-(N-2-phosphoethyl phosphoric acid)-amide,ω-carboxyl-bismethyoxy poly(ethylene glycol)(ADP-PEG-COOH),was synthesized as an in situ surface modifier to HA nanoparticles.The resulting modified HA(ADP-PEG-HA) can disperse in methanol,forming a colloid stabilized by peripheral carboxyl-endcapped PEG chains.The colloidal particles resembled nanospheres which agglomerated to some extent under examination by transmission electron microscope.This highly dispersible HA nanoparticles in organic solvent might find application in preparing new HA nanocomposites.     

Viscoelastic properties of single poly(ethylene glycol) molecules.

The viscoelastic properties of single poly(ethylene glycol) (PEG) molecules were measured by analysis of thermally and magnetically driven oscillations of an atomic force microscope (AFM) cantilever/molecule system. The molecular and monomer stiffness and friction of the PEG polymer were derived using a simple harmonic oscillator (SHO) model. Excellent agreement between the values of these two parameters obtained by the two approaches indicates the validity of the SHO model under the experimental regimes and the excellent reproducibility of the techniques. A sharp minimum in the monomeric friction is seen at around 180 pN applied force which we propose is due to a force induced change in the shape of the energy landscape describing the conformational transition of PEG from a helical to a planar state, which in turn affects the timescale of the transition and therefore modifies the measured internal friction. A knowledge of the viscoelastic response of PEG monomers is particularly important since PEG is widely used as a linker molecule for tethering groups of interest to the AFM tip in force spectroscopy experiments, and we show here that care must be exercised because of the force-dependent viscoelastic properties of these linkers.     

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     

Dynamic interfacial properties of poly(ethylene glycol)-modified ferritin at the solid/liquid interface

Poly(ethylene glycol)-modified ferritins (PEG-ferritins) with various molecular weights were synthesized by the grafting method, and their dynamic interfacial properties at the solid/liquid interface were investigated. The number of PEG grafted to ferritins was controlled by the amount of 1,1'-carbonyldiimidazole-modified PEG adding to the reaction solution. The adsorption kinetics and energy dissipation of PEG-ferritins onto bare Si substrate and amino-modified Si substrate were investigated with a quartz crystal microbalance (QCM) in 10 mM bis-Tris/HCl buffer (pH 5.8), while their morphologies were characterized by scanning electron microscopy (SEM). The adsorption dynamics of PEG-ferritins onto amino-modified Si substrate were quite different from those of unmodified ferritin, which can be reasonably interpreted by the desorption capability of PEG-ferritins on the surface attributed to amphiphilicity and the high-chain mobility of PEG chains.     

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.     

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%).     

Initiating efficiency of poly(ethylene glycol)-based initiators for transition metal mediated living radical polymerisation

The kinetics of the copper mediated living radical polymerisation of methyl methacrylate initiated by [poly(ethylene glycol) methyl ether]-based initiators (MeOPEG) of various molecular weights was followed by ¹H NMR. The initiator efficiency of the macroinitiators was investigated. It was found that temperature and solvent have little effect on the reactivity of the macroinitiator, whilst chain length affects greatly the MeOPEG initiating efficiency. Steric hindrance is thought to be a main drawback, as difficult access of the monomer to the MeOPEG active chain-end and coordination of the copper catalyst to the MeOPEG chains can prevent the monomer to react with the macroinitiator.     

Column packing for gas chromatography containing immobilized poly(ethylene glycol) stationary phase

Summary Carbowax 20M poly(ethylene glycol) stationary phase was immobilized on Chromosorb W by cross-linking with pluriisocyanate. The properties of the prepared packing material were investigated. Column efficiencies of 10,960 and 7,510 theoretical plates/meter were obtained for n-pentadecane and 1-heptanol, respectively.     

Complexes of poly(ethylene glycol)-based cationic random copolymer and calf thymus DNA: a complete biophysical characterization

Complete biophysical characterization of complexes (polyplexes) of cationic polymers and DNA is needed to understand the mechanism underlying nonviral therapeutic gene transfer. In this article, we propose a new series of synthesized random cationic polymers (RCPs) from methoxy poly(ethylene glycol) monomethacrylate (MePEGMA) and (3-(methacryloylamino)propyl)trimethylammonium chloride with different mole ratios (32:68, 11:89, and 6:94) which could be used as a model system to address and answer the basic questions relating to the mechanism of the interaction of calf thymus DNA (CT-DNA) and cationic polymers. The solubility of the complexes of CT-DNA and RCP was followed by turbidity measurements. It has been observed that complexes of RCP with 68 mol % MePEGMA precipitate near the charge neutralization point, whereas complexes of the other two polymers are water-soluble and stable at all compositions. Dnase 1 digestion experiments show that DNA is inaccessible when it forms complexes with RCP. Ethidium bromide exclusion and gel electrophoretic mobility show that both polymers are capable of binding with CT-DNA. Atomic force microscopy images in conjunction with light scattering experiments showed that the complexes are spherical in nature and 75-100 nm in diameter. Circular dichroism spectroscopy studies indicated that the secondary structure of DNA in the complexes is not perturbed due to the presence of poly(ethylene glycol) segments in the polymer. Furthermore, we used a combination of spectroscopic and calorimetric techniques to determine complete thermodynamic profiles accompanying the helix-coil transition of CT-DNA in the complexes. UV and differential scanning calorimetry melting experiments revealed that DNA in the complexes is more stable than in the free state and the extent of stability depends on the polymer composition. Isothermal titration calorimetry experiments showed that the binding of these RCPs to CT-DNA is associated with small exothermic enthalpy changes. A complete thermodynamic profile showed that the RCP/DNA complex formation is entropically favorable. Much broader opportunities to vary the architecture of the polymers studied here make these systems promising in addressing various basic and practical problems in gene delivery systems.     

Alkoxyacetyl (AAc) group as a useful linker for organic synthesis on poly(ethylene glycol) support

An alkoxyacetyl group (AAc) group was found to be an efficient linker for high-throughput synthesis of small molecules on a soluble polymer support. The linker allows high-yield loading of alcohols and phenols either by conventional carbodiimide-mediated esterification or transesterification using Yb(OTf)₃. Chemoselective cleavage to release small molecules is attained also by Yb(OTf)₃ or TMSCHN₂. The preparation, protocols for loading and releasing of small molecules, and an application to the Ugi four-component coupling reaction are reported.     

Rheological properties and phase behavior of a hydroxypropyl cellulose-poly(ethylene glycol) system

The relaxation and phase behavior of solutions of hydroxypropyl cellulose in poly(ethylene glycols) of various molecular masses has been studied by dynamic mechanical analysis. The dynamic mechanical data are compared with the results of microinterferometry and polarization-microscopy measurements. The combination of optical and mechanical characteristics makes it possible to construct generalized phase- relaxation diagrams for the binary systems under study. Solutions based on lowmolecular-mass poly(ethylene glycol) are characterized by LC equilibrium. With an increase in the molecular mass of poly(ethylene glycol) in a certain temperature-concentration region, amorphous phase separation takes place and the phase diagram is the superposition of LC and amorphous equilibria. The relaxation properties of the systems are sensitive to the phase state and its transformation.     

Poly(ethylene glycol) (PEG) as a reusable solvent medium for organic synthesis. Application in the Heck reaction

[reaction: see text] PEG has been used as a solvent medium for regioselective Heck reactions with easy recyclability of solvent and Pd catalyst for the first time.