On the elastic properties of single-walled carbon nanotubes/poly(ethylene oxide) nanocomposites using molecular dynamics simulations

Molecular dynamics simulations are used to study the physical and mechanical properties of single-walled carbon nanotubes/poly(ethylene oxide) nanocomposites. The effects of nanotube atomic structure, diameter, and volume fraction on the polymer density distribution, polymer atom distribution, stress–strain curves of nanocomposites and Young’s, and shear moduli of single-walled carbon nanotubes/poly(ethylene oxide) nanocomposites are explored. It is shown that the density of polymer, surrounding the nanotube surface, has a peak near the nanotube surface. However, increasing distance leads to dropping it to the value near the density of pure polymer. It is seen that for armchair nanotubes, the average polymer atoms distances from the single-walled carbon nanotubes are larger than the polymer atom distance from zigzag nanotubes. It further is shown that zigzag nanotubes are better candidates to reinforce poly (ethylene oxide) than their armchair counterparts.     

Solubilization of docetaxel in poly(ethylene oxide)-block-poly(butylene/styrene oxide) micelles

Poly(ethylene oxide)-block-poly(styrene oxide) (PEO-b-PSO) and PEO-b-poly(butylene oxide) (PEO-b-PBO) of different chain lengths were synthesized and characterized for their self-assembling properties in water by dynamic/static light scattering, spectrofluorimetry, and transmission electron microscopy. The resulting polymeric micelles were evaluated for their ability to solubilize and protect the anticancer drug docetaxel (DCTX) from degradation. The drug release kinetics as well as the cytotoxicity of the loaded micelles were assessed in vitro. All polymers formed micelles with a highly viscous core at low critical association concentrations (<10 mg/L). Micelle morphology depended on the nature of the hydrophobic block, with PBO- and PSO-based micelles yielding monodisperse spherical and cylindrical nanosized aggregates, respectively. The maximum solubilization capacity for DCTX ranged from 0.7 to 4.2% and was the highest for PSO micelles exhibiting the longest hydrophobic segment. Despite their high affinity for DCTX, PEO-b-PSO micelles were not able to efficiently protect DCTX against hydrolysis under accelerated stability testing conditions. Only PEO-b-PBO bearing 24 BO units afforded significant protection against degradation. In vitro, DCTX was released slower from the latter micelles, but all formulations possessed a similar cytotoxic effect against PC-3 prostate cancer cells. These data suggest that PEO-b-P(SO/BO) micelles could be used as alternatives to conventional surfactants for the solubilization of taxanes.     

Polycationic block copolymers of poly(ethylene oxide) and poly(propylene oxide) for cell transfection

A facile, one-step synthesis of cationic block copolymers of poly(2-N-(dimethylaminoethyl) methacrylate) (pDMAEMA) and copolymers of poly(propylene oxide) (PPO) and poly(ethylene oxide) (PEO) has been developed. The PEO-PPO-PEO-pDMAEMA (L92-pDMAEMA) and PEO-pDMAEMA copolymers were obtained via free radical polymerization of DMAEMA initiated by polyether radicals generated by cerium(IV). Over 95% of the copolymer fraction was of molecular mass ranging from 6.9 to 7.1 kDa in size, indicating the prevalence of the polyether-monoradical initiation mechanism. The L92-pDMAEMA copolymers possess parent surfactant-like surface activity. In contrast, the PEO-pDMAEMA copolymers lack significant surface activity. Both copolymers can complex with DNA. Hydrodynamic radii of the complexes of the L92-pDMAEMA and PEO-pDMAEMA with plasmid DNA ranged in size from 60 to 400 nm, depending on the copolymer/DNA ratio. Addition of Pluronic P123 to the L92-pDMAEMA complexes with DNA masked charges and decreased the tendency of the complex to aggregate, even at stoichiometric polycation/DNA ratios. The transfection efficiency of the L92-pDMAEMA copolymer was by far greater than that of the PEO-pDMAEMA copolymer. An extra added Pluronic P123 further increased the transfecton efficacy of L92-pDMAEMA, but did not affect that of PEO-pDMAEMA.     

Electrospinning Bombyx mori silk with poly(ethylene oxide)

Electrospinning for the formation of nanoscale diameter fibers has been explored for high-performance filters and biomaterial scaffolds for vascular grafts or wound dressings. Fibers with nanoscale diameters provide benefits due to high surface area. In the present study we explore electrospinning for protein-based biomaterials to fabricate scaffolds and membranes from regenerated silkworm silk, Bombyx mori, solutions. To improve processability of the protein solution, poly(ethylene oxide) (PEO) with molecular weight of 900,000 was blended with the silk fibroin. A variety of compositions of the silk/PEO aqueous blends were successfully electrospun. The morphology of the fibers was characterized using high-resolution scanning electron microscopy. Fiber diameters were uniform and less than 800 nm. The composition was estimated by X-ray photoelectron spectroscopy to characterize silk/PEO surface content. Aqueous-based electrospining of silk and silk/PEO blends provides potentially useful options for the fabrication of biomaterial scaffolds based on this unique fibrous protein.     

Heterobifunctional poly(ethylene oxide) oligomers containing carboxylic acids

Syntheses of vinylsilyl alcohols having one to three vinyl moieties and their use as initiators for ethylene oxide polymerizations are discussed. Poly(ethylene oxide) oligomers with vinylsilanes at one end and a hydroxyl group at the other were prepared in base-catalyzed reactions. Molecular weights determined from 1H NMR and gel permeation chromatography were close to the targeted values. Carboxylic acid functional poly(ethylene oxide) oligomers were prepared from ene-thiol addition reactions of mercaptoacetic acid across the vinylsilane terminus. It is anticipated that these carboxylic acid functional oligomers will complex to magnetite nanoparticles to afford complexes that can be dispersed in aqueous media.     

Biodegradable polymeric nanospheres formed by temperature-induced phase transition in a mixture of poly(lactide-co-glycolide) and poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer

The mixture of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer(F-127) and PLGA (poly(lactide-co-gycolide)) forms a liquid state above their phase transition temperatures, and the phase-separated state is induced by decreasing the temperature below the phase transition temperature. On the basis of the temperature-induced phase transition behavior in the mixture of F-127 and PLGA, a novel method for the preparation of drug-loaded PLGA nanospheres was designed and characterized by measuring the loading amount, the encapsulation efficiency, and the drug release pattern. Paclitaxel, used as a potent anticancer drug, was selected as a model drug.     

Poly(ethylene oxide sulfide): new poly(ethylene glycol) derivatives degradable in reductive conditions

Poly(ethylene oxide sulfide) (PEOS), polymers consisting of an internal ethylene oxide oligomer and disulfide linkage, were synthesized and characterized. The degree of polymerization was dependent upon temperature, dimethyl sulfoxide condition, and monomer hydrophobicity. The stability of PEOS was measured by the size exclusion chromatography method after the incubation both with and without 5 mM glutathione. The disulfide bond was stable in the extracellular condition but completely degraded in 2 h in the reductive cytosolic condition. Hydrophilic PEOS polymers showed no cytotoxicity on the HepG2 cell line. On the basis of these properties, PEOS can be applied in many drug delivery fields.     

Self-assembled poly(butadiene)-b-poly(ethylene oxide) polymersomes as paclitaxel carriers

In this work, self-assembled poly(butadiene)-b-poly(ethylene oxide) (PB-PEO) polymersomes (polymer vesicles) and worm micelles were evaluated as paclitaxel carriers. Paclitaxel was successfully incorporated into PB-PEO polymersomes and worm micelles. The loading capacity of paclitaxel inside PB-PEO colloids ranged from 6.7% to 13.7% w/w, depending on the morphology of copolymer colloids and the molecular weight of diblock copolymer. Paclitaxel loaded OB4 (PB219-PEO121) polymersome formulations were colloidally stable for 4 months at 4 degrees C and exhibited slow steady release of paclitaxel over a 5 week period at 37 degrees C. Evaluation of the in vitro cytotoxicity of paclitaxel-polymersome formulations showed that the ability of paclitaxel-loaded polymersomes to inhibit proliferation of MCF-7 human breast cancer cells was less compared to paclitaxel alone. By increasing the concentration of paclitaxel in polymersomes from 0.02 to 0.2 mug/mL, paclitaxel-polymersome formulations showed comparable activity in inhibiting the growth of MCF-7 cells. Taken together, these results demonstrate that paclitaxel-polymersomes have desirable restrained release profile and exhibit long-term stability.     

Poly(organo phosphazene) nanoparticles surface modified with poly(ethylene oxide)

The use of biodegradable derivatives of poly(organo phosphazenes) for the preparation of nanoparticles and their surface modification with the novel poly(ethylene oxide) derivative of poly(organo phosphazene) has been assessed using a range of in vitro characterization methods. The nanoparticles were produced by the precipitation solvent evaporation method from the derivative co-substituted with phenylalanine and glycine ethyl ester side groups. A reduction in particle size to less than 200 nm was achieved by an increase in pH of the preparation medium. The formation (and colloidal stability) of these nanoparticles seems to be controlled by two opposite effects: attractive hydrophobic interactions between phenylalanine ester groups and electrostatic repulsions arising from the carboxyl groups formed due to (partial) hydrolysis of the ester bond(s) at the high pH of the preparation medium. The poly[(glycine ethyl ester)phosphazene] derivative containing 5000-Da poly(ethylene oxide) as 5% of the side groups was used for the surface modification of nanoparticles. Adsorbed onto the particles, the polymer produced a thick coating layer of approximately 35 nm. The coated nanoparticles exhibited reduced surface negative potential and improved colloidal stability toward electrolyte-induced flocculation, relative to the uncoated system. However, the steric stabilization provided was less effective than that of a Poloxamine 908 coating. This difference in effectiveness of the steric stabilization might indicate that, although both the stabilizing polymers possess a 5000-Da poly(ethylene oxide) moiety, there is a difference in the arrangements of these poly(ethylene oxide) chains at the particle surface. (c) 1996 John Wiley & Sons, Inc.     

Small-angle X-ray scattering study of the interaction of poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) triblock copolymers with lipid bilayers

The relationship between molecular architecture and the nature of interactions with lipid bilayers has been studied for a series of poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymers using small-angle X-ray scattering (SAXS) and thermal analysis (differential scanning calorimetry, DSC). The number of molecular repeat units in the hydrophobic poly(propylene oxide), PPO, block has been found to be a critical determinant of the nature of triblock copolymer-lipid bilayer association. For dimyristoyl-sn-glycero-3-phosphocholine (DMPC)-based biomembrane structures, polymers possessing a PPO chain length commensurate with the acyl chain dimensions of the lipid bilayer yield highly ordered, swollen lamellar structures consistent with well-integrated (into the lipid bilayer) PPO blocks. Triblock copolymers of lesser PPO chain length yield materials with structural characteristics similar to a simple dispersion of DMPC in water. Increasing the concentration (from 4 to 12 mol %) of well-integrated triblock copolymers enhances the structural ordering of the lamellar phase, while concentrations exceeding 16 mol % result in the formation of a hexagonal phase. Examination of temperature-induced changes in the structure of these mesophases (complex fluids) reveals that if the temperature is reduced sufficiently, all compositions exclude polymer and thus exhibit the characteristic SAXS pattern for hydrated DMPC bilayers. Increasing the temperature promotes better insertion of the polymers possessing PPO chain lengths sufficient for membrane insertion. No temperature-induced structural changes are observed in compositions prepared with PEO-PPO-PEO polymers that feature PPO length insufficient to permit full incorporation into the lipid bilayer.     

A convenient method for the synthesis of amine-terminated poly(ethylene oxide) and poly(epsilon-caprolactone)

A convenient synthetic route to prepare amine-terminated poly(ethylene oxide) (PEO) and poly(epsilon-caprolactone) (PCL) was described. The strategy involved two-step reactions, the condensation of hydroxyl-terminated PEO and PCL with N-benzyloxycarbonyl amino acid followed by the catalytic hydrogenation under mild conditions. NMR and GPC measurements indicated that the reactions proceeded nearly quantitatively. Amine-terminated PEO thus prepared was used to initiate the polymerization of alpha-(N(epsilon)-benzyloxycarbonyl-L-lysine) N-carboxy anhydride [lys(Z)-NCA], and the results confirmed that the reactivity of the amino group was high.     

Poly(ethylene oxide)-b-poly(L-lactide) diblock copolymer/carbon nanotube-based nanocomposites: LiCl as supramolecular structure-directing agent

This work relies on the CNT dispersion in either solution or a polymer matrix through the formation of a three-component supramolecular system composed of PEO-b-PLLA diblock copolymer, carbon nanotubes (CNTs), and lithium chloride. According to a one-pot procedure in solution, the "self-assembly" concept has demonstrated its efficiency using suspension tests of CNTs. Characterizations of the supramolecular system by photon correlation spectroscopy, Raman spectroscopy, and molecular dynamics simulations highlight the charge transfer interaction from the CNTs toward the PEO-b-PLLA/LiCl complex. Finally, this concept was successfully extended in bulk (absence of solvent) via melt-processing techniques by dispersing these complexes in a commercial polylactide (PLA) matrix. Electrical conductivity measurements and transmission electron microscopy attested for the remarkable dispersion of CNTs, confirming the design of high-performance PLA-based materials.     

Modeling and experimental investigation of rheological properties of injectable poly(lactide ethylene oxide fumarate)/hydroxyapatite nanocomposites

Injectable multiphasic polymer/ceramic composites are attractive as bioresorbable scaffolds for bone regeneration because they can be cross-linked in situ and are osteoconductive. The injectability of the composite depends on the nanoparticle content and the energetic interactions at the polymer/particle interface. The objective of this research was to determine experimentally the rheological properties of the PLEOF/apatite composite as an injectable biomaterial and to compare the viscoelastic response with the predictions of a linear elastic dumbbell model. A degradable in situ cross-linkable terpolymer based on low molecular weight poly(L-lactide) and poly(ethylene oxide) linked by unsaturated fumarate groups is synthesized. The poly(L-lactide-co-ethylene oxide-co-fumarate) (PLEOF) terpolymer interacts with the surface of the apatite nanoparticles by polar interactions and hydrogen bonding. A kinetic model is developed that takes into account the adsorption/desorption of polymer chains to/from the nanoparticle surface. Rheological properties of the aqueous dispersion of PLEOF terpolymer reinforced with nanosized hydroxyapatite (HA) particles are investigated using mechanical rheometry. To this end, we performed a series of rheological experiments on un-cross-linked PLEOF reinforced with different volume fractions of HA nanoparticles. The results demonstrate that the observed nonlinear viscoelasticity at higher shear rates is controlled by the energetic interactions between the polymer chains and dispersed particle aggregates and by the rate of the adsorption/desorption of the chains to/from the surface of the nanoparticles.     

Mannosylated poly(ethylene oxide)-b-poly(epsilon-caprolactone) diblock copolymers: synthesis, characterization, and interaction with a bacterial lectin

A novel bioeliminable amphiphilic poly(ethylene oxide)-b-poly(epsilon-caprolactone) (PEO-b-PCL) diblock copolymer end-capped by a mannose residue was synthesized by sequential controlled polymerization of ethylene oxide and epsilon-caprolactone, followed by the coupling of a reactive mannose derivative to the PEO chain end. The anionic polymerization of ethylene oxide was first initiated by potassium 2-dimethylaminoethanolate. The ring-opening polymerization of epsilon-caprolactone was then initiated by the omega-hydroxy end-group of PEO previously converted into an Al alkoxide. Finally, the saccharidic end-group was attached by quaternization of the tertiary amine alpha-end-group of the PEO-b-PCL with a brominated mannose derivative. The copolymer was fully characterized in terms of chemical composition and purity by high-resolution NMR spectroscopy and size exclusion chromatography. Furthermore, measurements with a pendant drop tensiometer showed that both the mannosylated copolymer and the non-mannosylated counterpart significantly decreased the dichloromethane/water interfacial tension. Moreover, these amphiphilic copolymers formed monodisperse spherical micelles in water with an average diameter of approximately 11 nm as measured by dynamic light scattering and cryo-transmission electron microscopy. The availability of mannose as a specific recognition site at the surface of the micelles was proved by isothermal titration microcalorimetry (ITC), using the BclA lectin (from Burkholderia cenocepacia), which interacts selectively with alpha-D-mannopyranoside derivatives. The thermodynamic parameters of the lectin/mannose interaction were extracted from the ITC data. These colloidal systems have great potential for drug targeting and vaccine delivery systems.     

Cellular internalization of poly(ethylene oxide)-b-poly(epsilon-caprolactone) diblock copolymer micelles

Poly(ethylene oxide)-b-poly(epsilon-caprolactone) (PEO-b-PCL) block copolymers self-assemble into micelles in aqueous solution. We have examined whether these micelles can internalize into P19 cells in vitro. Fluorescently labeled PEO(45)-b-PCL(23) block copolymer was prepared by conjugating a tetramethylrhodamine molecule to the end of the hydrophobic PCL block. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) studies yielded 24 +/- 2 and 25 +/- 2 nm, respectively, for the diameters of the micelles. The studies also showed that chemical labeling did not effect the morphology or size. When the rhodamine-labeled PEO(45)-b-PCL(23) block copolymer micelles were tested in vitro, time-, concentration-, and pH-dependence of the internalization process suggested that internalization proceeded by endocytosis. The results from these studies provide the first direct evidence for the internalization of PEO(45)-b-PCL(23) micelles. Future studies will utilize multiple labeling of these micelles, allowing questions to be addressed related to the fate of internalized micelles as drug carriers, the destination of the incorporated drugs or fluorescent probes released from micelles, and the identification of the subcellular localization of the whole drug-carrier system within cells, both in vitro and in vivo.     

Electrospun sodium alginate/poly(ethylene oxide) core-shell nanofibers scaffolds potential for tissue engineering applications

Core-shell structure nanofibers of sodium alginate/poly(ethylene oxide) were prepared via electrospinning their dispersions in water solution. The core-shell structure morphology of the obtained nanofibers was viewed under scanning electron microscope (SEM) and transmission electron microscope (TEM), and X-ray photoelectron spectroscopy (XPS) analysis was used to further quantify the chemical composition of the core-shell composite SA/PEO nanofibers surface in detail. Furthermore, one-step cross-linking method through being immersed in CaCl₂ solution was investigated to improve the anti-water property of the electrospun nanofibers mats in order to facilitate their practical applications as tissue engineering scaffolds, and the changes of the structural of nanofibers before and after cross-linking was characterized by Fourier transform infrared (FT-IR). Indirect cytotoxicity assessment indicated that SA/PEO nanofibers membrane was nontoxic to the fibroblasts cells, and cell culture suggested that SA/PEO nanofibers tended to promote fibroblasts cells attachment and proliferation. It was assumed that the nanofibers membrane of electrospun SA/PEO could be used for tissue engineering scaffolds.     

Biomaterial films of Bombyx mori silk fibroin with poly(ethylene oxide)

Phase separation into controllable patterned microstructures was observed for Bombyx mori silkworm silk and poly(ethylene oxide) (PEO) (900000 g/mol) blends cast from solution. The evolution of the microstructures with increasing PEO volume fraction is strikingly similar to the progression of phases and microstructures observed with surfactants. The chemically patterned materials obtained provide engineerable biomaterial surfaces with predictable microscale features which can be used to create topographically patterned or chemically functionalized biomaterials. Solution blending was used to incorporate water-soluble PEO into silk to enhance elasticity and hydrophilicity. The sizes of the globule fibroin phase ranged from 2.1 +/- 0.5 to 18.2 +/- 2.1 microm depending on the ratio of silk/PEO. Optical microscopy and SEM analysis confirmed the micro-phase separation between PEO and silk. Surface properties were determined by XPS and contact angle. Methanol can be used to control the conformational transition of silk fibroin to the insoluble beta-sheet state. Subsequentially, the PEO can be easily extracted from the films with water to generate silk matrixes with definable porosity and enhanced surface roughness. These blend films formed from two biocompatible polymers provide potential new biomaterials for tissue engineering scaffolds.     

Protein-resistant silicones: incorporation of poly(ethylene oxide) via siloxane tethers

Silicones with enhanced protein resistance were prepared by introducing poly(ethylene oxide) (PEO) chains via siloxane tethers (a-c) of varying lengths. Three unique ambifunctional molecules (a-c) having the general formula alpha-(EtO)3Si(CH2)2-oligodimethylsiloxanen-block-poly(ethylene oxide)8-OCH3 (n = 0 (a), 4, (b), and 13 (c)) were prepared via regioselective Rh-catalyzed hydrosilylation. Nine films were subsequently produced by the H3PO4-catalyzed sol-gel cross-linking of a-c each with alpha,omega-bis(Si-OH)polydimethylsiloxane (P, Mn = 3000 g/mol) in varying ratios (1:1, 1:2, and 2:3 molar ratio a, b, or c to P). Films prepared with a 2:3 molar ratio (a-c to P) contained the least amount of un-cross-linked materials, which may migrate to the film surface. For this set of films, surface hydrophilicity and protein resistance increased with siloxane tether length (a-c). These results indicate that PEO was more effectively mobilized to the surface if incorporated into silicones via longer siloxane tethers.     

Separation and recovery of DNA fragments by electrophoresis through a thermoreversible hydrogel composed of poly(ethylene oxide) and poly(propylene oxide)

We have synthesized and characterized a thermoreversible hydrogel of multiplied block copolymers, composed of poly(ethylene oxide) and poly(propylene oxide), for DNA electrophoresis. The aqueous solution of block copolymers turned into a hydrogel upon heating at temperatures above 10-11 degrees C, whereas it reverted into a solution upon cooling. Linear double-stranded DNA molecules migrated through the gel matrices at a rate that was inversely proportional to the logarithm of the DNA length. The hydrogel is most effective for separating DNA fragments in the 10- to 2000-bp range. The resolving range lay in-between the effective ranges of polyacrylamide and agarose gel electrophoreses of DNA. The gel slices containing DNA fragments were liquefied by cooling on ice, and the DNA was precipitated with ethanol. No contaminants that inhibit enzymatic reactions were found in the DNA recovered from the hydrogel. Plasmid DNA recovered from the hydrogel was recircularized with T4 DNA ligase and yielded highly efficient Escherichia coli transformation. Therefore, thermoreversible gel electrophoresis will be a useful method for DNA separation and isolation in recombinant DNA technology.     

Phase separation in the mixture of schizophyllan and poly(ethylene oxide) in aqueous solution driven by a specific interaction between the glucose side chain and poly(ethylene oxide)

We found that the mixture of schizophyllan and poly(ethylene oxide) in aqueous solution underwent phase separation at around 3-4 degrees C, and this temperature was independent of both polymer concentration and the difference in poly(ethylene oxide) molecular weight (Mw 6000 and 70,000). The phase-separation took place at the same temperature at which the optical rotation changed. Since the optical rotation change is ascribed to the difference in the nature of hydrogen bonding between the schizophyllan side chain and water, the phase separation is also considered to be due to an interaction between poly(ethylene oxide) and schizophyllan. The phase-separation temperature increased on changing H2O to D2O in accordance with a change in the optical rotation, confirming the specific interaction essential for the phase separation.