Poly(butyl methacrylate-g-methoxypoly(ethylene glycol)) and poly(methyl methacrylate-g-methoxypoly(ethylene glycol)) graft copolymers: preparation and aqueous solution properties

A series of water-soluble, amphiphilic graft copolymers has been prepared by free-radical copolymerization of methoxypoly(ethylene glycol) macromonomers, with either methyl methacrylate or butyl methacrylate as the comonomers, in water/ethanol solvent mixtures. Lower molecular weight copolymers were obtained by increasing the concentration of the initiator, azobisisobutyronitrile (AIBN), used in the polymerization reaction. However, the route used also led to the formation of significant quantities of tetramethylsuccinodinitrile, a toxic byproduct resulting from the cage reaction of AIBN. Static fluorescence measurements using pyrene as a probe, along with 1H NMR experiments, showed that the graft copolymers form aggregates in water at very low concentrations (approximately 0.01 g l(-1)) with the pendant hydrophilic graft chains forming a stabilizing shell around the hydrophobic backbone. An increase in the hydrophile-lipophile balance of the graft copolymers was found to lead to smaller aggregates with lower aggregation numbers and highly swollen hydrophilic shells, as revealed by small angle neutron scattering (SANS).     

Effects of SDS on the thermo- and pH-sensitive structural changes of the poly(acrylic acid)-based copolymer containing both poly(N-isopropylacrylamide) and monomethoxy poly(ethylene glycol) grafts in water

The effects of SDS on the structural changes of the thermally induced polymeric micelles from a graft copolymer comprising poly(acrylic acid) (PAAc) as the backbone and poly(N-isopropylacrylamide) (PNIPAAm) and monomethoxy poly(ethylene glycol) (mPEG) as the grafts in aqueous solution are studied. At low temperature, SDS micelles form via the hydrophobic association of SDS molecules with the PNIPAAm grafts at a critical aggregation concentration of SDS (cac(SDS)) much lower than its critical micelle concentration. Consequently, the critical aggregation temperature of the graft copolymer is elevated. The corresponding structure of the thermally induced polymeric micelles is characterized by an abrupt reduction in the particle size and an increased tendency toward formation of the monocore structure with a more compact and hydrophobic PNIPAAm microdomain being developed. On the other hand, upon the polymeric micelle formation at high temperature, the copolymer-bound SDS micelle structure is disrupted and the dissociated SDS molecules migrate to the core-shell interface with their alkyl chains residing in the liquidlike region of the hydrophobic PNIPAAm microdomain. The correlation between the polymeric particles and copolymer-bound micelles is further substantiated by showing the change of the colloidal particle size in response to changes in cac(SDS) via adjusting the pH of the aqueous copolymer/SDS solutions.     

Small-angle neutron scattering and theoretical investigation of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) stabilized oil-in-water microemulsions

The aim of this study is to determine the effects of oil solutes and alcohol cosolvents on the structure of oil-in-water microemulsions stabilized by poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymers. The systems investigated involved the solubilization of 1,3,5-trimethylbenzene or 1,2-dichlorobenzene by P123 (EO(20)-PO(70)-EO(20)) pluronic surfactant micelles in water and water + ethanol solvents. The structures of these swollen micelles were determined by small-angle neutron scattering (SANS). A thermodynamic model was employed to interpret the characterization data. The results of the thermodynamic model for micellization agreed well with the SANS data from samples of micelles swollen by both oils. The model predicted the size of the micelles within 5% accuracy using only one fitting parameter, the micelle polydispersity. Ethanol had significantly different effects on the polymer micelles that contained solubilized oil compared to pure polymer micelles. For pure polymer micelles, the addition of ethanol increased the solubility of the polymer and, therefore, decreased the total volume fraction of micelles, while for polymer-oil aggregates, ethanol tended to have a positive effect on the volume fraction of micelles. SANS results showed that the greatest divergence from pure aqueous solvent results occurred at oil concentrations above the microemulsion stability limit.     

Poly(ethylene glycol)-b-poly(epsilon-caprolactone) and PEG-phospholipid form stable mixed micelles in aqueous media

Novel mixed polymeric micelles formed from biocompatible polymers, poly(ethylene glycol)-b-poly(epsilon-caprolactone) (PEG(5000)-b-PCL(x)) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy poly(ethylene glycol) (PEG-DSPE), possess small size and high thermodynamic stability, raising their potential as long circulating carriers in the context of delivery of antineoplastic and antibiotic drugs. Formation of mixed polymeric micelles was confirmed using size exclusion chromatography and 1H NMR NOESY. Steady-state fluorescence measurements revealed depressed critical micellar concentrations indicative of a cooperative interaction between component hydrophobic blocks, which was quantified using the pseudophase model for micellization. Steady-state fluorescence measurements indicated that the mixed polymeric micelle cores possess intermediate micropolarity and high microviscosity. Pulsed field gradient spin-echo measurements were used to characterize micellar diffusion coefficients, which agree well with those obtained using dynamic light scattering. NOE spectra suggested that the hydrophobic polymer segments from individual components are in close proximity, giving evidence for the formation of a relatively homogeneous core. Contrary to one-component PEG(5000)-b-PCL(x) micelles, the mixed polymeric micelles could incorporate clinically relevant levels of the poorly water soluble antibiotic, amphotericin B (AmB). AmB encapsulation and release studies revealed an interesting composition-dependent interaction of the drug with the mixed polymeric micelle core.     

Micellization and gelation of aqueous solutions of star-shaped PEG-PCL block copolymers consisting of branched 4-arm poly(ethylene glycol) and polycaprolactone blocks

Star-shaped block copolymers consisting of non-toxic poly(ethylene glycol) and biodegradable polycaprolactone ((PEG5K-PCL)₄) were synthesized by ring-opening polymerization of the ε-caprolactone monomer with hydroxyl-terminated 4-armed PEG as initiator. These biodegradable, amphiphilic star block copolymers showed micellization and sol-gel transition behaviors in aqueous solution with varying concentration and temperature. In the dilute aqueous solutions of star block copolymers, micellization behavior occurred over specific concentration. The 1,6-diphenyl-1,3,5-hexatriene (DPH) solubilization method was used to determine the critical micellization concentration (CMC) of star block copolymers. The obtained micelle size increased with increasing hydrophobic PCL block length. In high-concentration solutions, the star block copolymers showed temperature-sensitive sol-gel transition behavior. The morphology of the micelle and gel was investigated by atomic force microscopy (AFM). As a result, the micelles showed a core-corona spherical structure at concentration near CMC, while the gel showed a mountain-chain-like morphology picture. It was proposed that with increasing the micelle concentration the worm-like micelle clusters formed firstly and the gel was constructed by the packing of micelle clusters.     

Synthesis of poly[N‐isopropylacrylamide‐g‐poly(ethylene glycol)] with a reactive group at the poly(ethylene glycol) end and its thermosensitive self‐assembling character

Poly[N‐isopropylacrylamide‐g‐poly(ethylene glycol)]s with a reactive group at the poly(ethylene glycol) (PEG) end were synthesized by the radical copolymerization of N‐isopropylacrylamide with a PEG macromonomer having an acetal group at one end and a methacryloyl group at the other chain end. The temperature dependence of the aqueous solutions of the obtained graft copolymers was estimated by light scattering measurements. The intensity of the light scattering from aqueous polymer solutions increased with increasing temperature. In particular, at temperatures above 40°C, the intensity abruptly increased, indicating a phase separation of the graft copolymer due to the lower critical solution temperature (LCST) of the poly(N‐isopropylacrylamide) segment. No turbidity was observed even above the LCST, and this suggested a nanoscale self‐assembling structure of the graft copolymer. The dynamic light scattering measurements confirmed that the size of the aggregate was in the range of several tens of nanometers. The acetal group at the end of the PEG graft chain was easily converted to the aldehyde group by an acid treatment, which was analyzed by ¹H NMR. Such a temperature‐induced nanosphere possessing reactive PEG tethered chains on the surface is promising for new nanobased biomedical materials. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 1457–1469, 2006     

Thermogelling polymers composed of poly(cyclohexylenedimethylene adipate) and poly(ethylene glycol)

Block copolymers composed of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic biodegradable polyesters have been reported as thermogelling polymers, because they feature temperature-dependent sol-to-gel or gel-to-sol transitions in aqueous solutions. In this study, a series of thermogelling poly(ethylene glycol methyl ether)-block–poly(cyclohexylenedimethylene adipate)-block–poly(ethylene glycol methyl ether) triblock copolymers and PEG-block–poly(cyclohexylenedimethylene adipate) multiblock copolymers was synthesized by reacting hydroxyl-terminated poly(cyclohexylenedimethylene adipate) (PCA) with poly(ethylene glycol methyl ether) and PEG, respectively, using 1,6-diisocyanatohexane as the coupling agent. Two hydroxyl-terminated PCAs, i.e., poly(1,4-cyclohexylenedimethylene adipate) and poly(1,3/1,4-cyclohexylenedimethylene adipate), were synthesized by the condensation reaction of adipic acid (AA) with 1,4-cyclohexanedimethanol (CHDM) and 1,3/1,4-CHDM, respectively, and used as the hydrophobic polyester blocks of these thermogelling copolymers to compare the effect of crystallinity on the sol-to-gel transition behavior.The polymers were characterized using proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, gel permeation chromatography, differential scanning calorimetry, solubility testing, and rheological analysis. Experimental results revealed that the structure of the PCA block (crystalline vs. amorphous), the molecular weights of the hydrophobic PCA and hydrophilic PEG blocks, and the type of thermogelling polymer (triblock vs. multiblock) influenced the solubility, polymer micelle packing characteristics, maximum storage modulus, and sol-to-gel temperature of the polymers. Among all the samples at 40 wt.% aqueous solutions, triblock copolymer TB3 showed sol-to-gel temperature at 22 °C, and had the highest maximum storage modulus about 170 Pa.     

Aqueous solution properties of amphiphilic triblock copolymer poly(p-dioxanone-co-l-lactide)-block-poly(ethylene glycol)

A poly(ethylene glycol) (PEG)-based new amphiphilic block copolymer bearing the poly(p-dioxanone-co-l-lactide) (PPDO/PLLA) hydrophobic moieties was prepared. Depending on the copolymer composition and molecular weights, solubility of the polymeric samples in water was varied. Its diluted aqueous solution properties were studied by viscometry, dye solubilization, ¹H-NMR and dynamic light scattering. 1,6-Diphenyl-1,3,5-hexatriene solubilization and ¹H-NMR spectra carried out in CDCl₃ and D₂O were used to prove the existence of hydrophobic domains as the core of micelle. Average particle size of 60-165 nm with low polydispersity and lower negative zeta (ξ) potential of −3 to −14 mV were observed on the aqueous copolymer dispersion.     

Molecular structure and dynamics of poly(methacrylic acid) and poly(acrylic acid) complexes with dodecyl-substituted poly(ethylene glycol)

The molecular dynamics and the structure of molecular complexes formed by micelles of dodecyl-substituted poly(ethylene glycol) with poly(methacrylic acid) and poly(acrylic acid) in aqueous solutions were studied by viscosimetry, pH measurement, and electron spin resonance spin-probe techniques. At low surfactant concentrations, the conformation of the complex is a compact globule. The local mobility of surfactant molecules in such a complex is much slower than that in the free micelle. At high surfactant concentration, the nonionic micelles and polyacids form hydrophilic associates. The associates have the conformation of extended coils. In an associate, a major part of the micellar poly(ethylene glycol) groups is free. The local mobility of the micellar phase depends on the number of micelles involved in an associate. The mobility of surfactant molecules is slower in the complexes of poly(methacrylic acid) than in the complexes of poly(acrylic acid).     

Synthesis and micellization of amphiphilic poly(sebacic anhydride)–poly(ethylene glycol)–poly(sebacic anhydride) block copolymers

Amphiphilic biodegradable block copolymers [poly(sebacic anhydride)–poly(ethylene glycol)–poly(sebacic anhydride)] were synthesized by the melt polycondensation of poly(ethylene glycol) and sebacic anhydride prepolymers. The chemical structure, crystalline nature, and phase behavior of the resulting copolymers were characterized with ¹H NMR, Fourier transform infrared, gel permeation chromatography, and differential scanning calorimetry. Microphase separation of the copolymers occurred, and the crystallinity of the poly(sebacic anhydride) (PSA) blocks diminished when the sebacic anhydride unit content in the copolymer was only 21.6%. ¹H NMR spectra carried out in CDCl₃ and D₂O were used to demonstrate the existence of hydrophobic PSA domains as the core of the micelle. In aqueous media, the copolymers formed micelles after precipitation from water‐miscible solvents. The effects on the micelle sizes due to the micelle preparation conditions, such as the organic phase, dropping rate of the polymer organic solution into the aqueous phase, and copolymer concentrations in the organic phase, were studied. There was an increase in the micelle size as the molecular weight of the PSA block was increased. The diameters of the copolymer micelles were also found to increase as the concentration of the copolymer dissolved in the organic phase was increased, and the dependence of the micelle diameters on the concentration of the copolymer varied with the copolymer composition. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 1271–1278, 2006     

Surface activity of new invertible amphiphilic polyesters based on poly(ethylene glycol) and aliphatic dicarboxylic acids

The surface active properties of aqueous solutions of invertible amphiphilic alternated polyesters differing by hydrophilic-lipophilic balance (HLB) and molecular weight have been determined over the wide concentration range. The polyesters are based on poly(ethylene glycol) (PEG) of two molecular weights and aliphatic dicarboxylic acids (decanedioic and dodecanedioic). The surface activity of the polyesters and their ability to form micellar assemblies (which was recently shown for organic solvents) has been confirmed in water. The central role of the balance of hydrophilic to hydrophobic groups ratio in the formation of polymeric arrangements having hydrophobic pockets and external hydrophilic shell has been shown. The effect of molecular weight has been found considerable as well. Two changes in slope have been observed for the more hydrophobic polyesters in the surface tension vs log concentration curve. The change at low concentration is believed to originate from the formation of polyester assemblies with a hydrophobic interior and hydrophilic exterior due to the interaction of hydrophobic fragments and macromolecular flexibility. The higher concentration region exhibits behavior consistent with a cmc, which was confirmed by additional dye solubilization experiments. Molecular structure of the polyester micelles is determined by the solubilization of a solvatochromic dye. The experiment confirmed that micellization of polyesters is accompanied by the association of more hydrophobic (aliphatic) constituents forming the micelle interior. The hydrophilic fragments (ethylene oxide groups) are involved in the formation of micelle exterior.     

Interaction between poly(ethylene glycol) and two surfactants investigated by diffusion coefficient measurements

Dynamic light scattering (DLS) and fluorescence recovery after pattern photobleaching (FRAPP) were used to study the interaction of low molecular weight poly(ethylene glycol) (PEG) with micelles of two different surfactants: tetradecyldimethyl aminoxide (C(14)DMAO, zwitterionic) and pentaethylene glycol n-dodecyl monoether (C(12)E(5), non-ionic). By using an amphiphilic fluorescent probe or a fluorescent-labeled PEG molecule, FRAPP experiments allowed to follow the diffusion of the surfactant-polymer complex either by looking at the micelle diffusion or at the polymer diffusion. Experiments performed with both fluorescent probes gave the same diffusion coefficient showing that the micelles and the polymer form a complex in dilute solutions. Similar experiments showed that PEG interacts as well with pentaethylene glycol n-dodecyl monoether (C(12)E(5)).     

Synthesis and self-assembly properties of a novel [poly(ethylene glycol)]-fluorocarbon-phospholipid triblock copolymer

The synthesis of a novel poly(ethylene glycol)-fluorocarbon-phospholipid conjugate that self-assembles into hyper-stable micelles characterized by an internal fluorous phase is described. Physical characterization of the micelles formed by this polymer in aqueous solution is included. Dynamic light scattering (DLS) measurements indicate a mean diameter of 15 nm (±3 nm), while pyrene fluorescence studies show a critical micelle concentration (CMC) of only 0.65 μM.     

Solubilization of n-alkylbenzenes into octaethylene glycol mono-n-tetradecyl ether (C14E8) micelles

Solubilization of benzene, toluene, ethylbenzene, n-propylbenzene, n-butylbenzene, and n-pentylbenzene into the micelles of octaethylene glycol monotetradecyl ether (C(14)E(8)) was studied, where equilibrium concentrations of all the solubilizates were determined spectrophotometrically at 298.2, 303.2, and 308.2 K. The concentration of the above solubilizates except benzene remained constant below the critical micelle concentration (cmc) and increased linearly with an increase in C(14)E(8) concentration above the cmc, whereas benzene concentration was found to remain constant over the whole concentration range of C(14)E(8). The Gibbs energy change (DeltaG(0)) for their solubilization was evaluated by the partitioning of the solubilizates between the aqueous phase and the micellar phase because of the large aggregation number of the C(14)E(8) micelle. Furthermore, enthalpy and entropy changes for their solubilization were evaluated from the temperature dependence of the DeltaG(0) values. From these thermodynamical parameters and the change in absorption spectra of the solubilizates due to their incorporation into the micelles, the solubilization site was found to move into the inner core of the micelle with increasing alkyl chain length of the solubilizates.     

Hierarchically organized micellization of thermoresponsive rod‐coil copolymers based on poly[oligo(ethylene glycol) methacrylate] and poly(ε‐caprolactone)

A series of amphiphilic triblock copolymers, poly[oligo(ethylene glycol) methacrylate]_x‐block‐poly(ε‐caprolactone)‐block‐poly[oligo(ethylene glycol) methacrylate]_x, POEGMA_Co(x), were synthesized. Formation of hydrophobic domains as cores of the micelles was studied by fluorescence spectroscopy. The critical micelle concentrations in aqueous solution were found to be in the range of circa 10^?6 M. A novel methodology by modulated temperature differential scanning calorimetry was developed to determine critical micelle temperature. A significant concentration dependence of cmt was found. Dynamic light scattering measurements showed a bidispersed size distribution. The micelles showed reversible dispersion/aggregation in response to temperature cycles with lower critical solution temperature between 75 and 85 °C. The interplay of the two hydrophobic and one thermoresponsive macromolecular chains offers the chance to more complex morphologies. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Effect of the structure of amphiphilic poly(ethylene glycol)‐containing graft copolymers on styrene emulsion polymerization

Amphiphilic graft copolymers consisting of monomeric units of poly(ethylene glycol) monomethyl ether acrylate, lauryl or stearyl methacrylate, and 2‐hydroxyethyl methacrylate were synthesized and characterized. The effectiveness of these poly(ethylene glycol)‐containing graft copolymers in stabilizing styrene emulsion polymerization was evaluated. The polymerization rate (R_p) increases with increasing graft copolymer concentration, initiator concentration, or temperature. At a constant graft copolymer concentration, R_p increases, and the amount of coagulum decreases with the increasing hydrophilicity of graft copolymers. The polymerization system does not follow Smith–Ewart case II kinetics. The desorption of free radicals out of latex particles plays an important role in the polymerization kinetics. The overall activation energy and the activation energy for the radical desorption process are 85.4 and 34.3 kJ/mol, respectively. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 1608–1624, 2002     

Ion conductivity studies of blends of poly(methyl methacrylate)-g-poly(ethylene glycol) and poly(ethylene glycol) complexed with LiCF3 SO3

Polymer electrolytes which are adhesive, transparent, and stable to atmospheric moisture have been prepared by blending poly(methyl methacrylate)-g-poly(ethylene glycol) with poly(ethylene glycol)/LiCF₃ SO₃ complexes. The maximum ionic conductivities at room temperature were measured to be in the range of 10⁻⁴ to 10⁻⁵ s cm⁻¹. The clarity of the sample was improved as the graft degree increased for all the samples studied. The graft degree of poly(methyl methacrylate)-g-poly(ethylene glycol) was found to be important for the compatibility between the poly(methyl methacrylate) segments in poly(methyl methacrylate)-g-poly(ethylene glycol) and the added poly(ethylene glycol), and consequently, for the ion conductivity of the polymer electrolyte. These properties make them promising candidates for polymer electrolytes in electrochromic devices. © 1996 John Wiley & Sons, Inc.     

Synthesis of amphiphilic poly(ether-amide) dendrimer endcapped with poly(ethylene glycol) grafts and its solubilization to salicylic acid

An amphiphilic dendrimer (DPEA-PEG) grafting polyethylene glycol at the terminals was prepared by endcapping of dendritic poly(ether-amide) (DPEA) with isocyanate terminated linear polyethylene glycol (PEG-NCO). The molecular structure was verified by gel permeation chromatography (GPC), ¹H NMR and FT-IR. The micelle characteristic of DPEA-PEG in water was investigated. The critical micelle concentration (CMC) was determined by a fluorescence technique to be 55.5 mg/L. The hydrodynamic radius of micelles was measured by dynamic light scattering (DLS) to be 76.2 nm. The UV–vis spectrum showed that the solubility of salicylic acid increased from 1.91 to 2.78 mg/L when the concentration of DPEA-PEG attained 5 mg/mL in an aqueous solution.     

微乳液聚合制备聚(甲基丙烯酸丁酯-乙烯基吡咯烷酮)纳米粒子

以BPO和FeSO4为氧化还原引发体系,使用非离子型的乳化剂吐温80,在低乳化剂浓度下(w<0.06)进行甲基丙烯酸丁酯和乙烯基吡咯烷酮的微乳液聚合,制备了粒径窄分布的纳米乳胶粒子。研究了微乳液聚合的引发方式、单体配比和单体加入方式对聚合反应、乳胶粒子粒径及其分布的影响,分析了界面引发微乳液聚合的机制。     

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.