"Schizophrenic" Hemocompatible Copolymers via Switchable Thermoresponsive Transition of Nonionic/Zwitterionic Block Self-Assembly in Human Blood

"Schizophrenic" diblock copolymers containing nonionic and zwitterionic blocks were prepared with well-controlled molecular weights via atom-transfer radical polymerization (ATRP). In this work, we report a systematic study of how morphological changes of poly(N-isopropylacrylamide)-block-poly(sulfobetaine methacrylate) (PNIPAAm-b-PSBMA) copolymers affect hemocompatibility in human blood solution. The "schizophrenic" behavior of PNIPAAm-b-PSBMA was observed by (1)H NMR, dynamic light scattering (DLS), and turbidity measurement with double morphological transition, exhibiting both lower critical solution temperature (LCST) and upper critical solution temperature (UCST) in aqueous solution. Below the UCST of PSBMA block, micelles were obtained with a core of insoluble PSBMA association and a shell of soluble PNIPAAm, whereas the opposite micelle structure was observed above the LCST of PNIPAAm block. In between the UCST and LCST, unimers with both soluble blocks were detected. Hydrodynamic size of prepared polymers and copolymers is determined to illustrate the correlations between intermolecular nonionic/zwitterionic associations and blood compatibility of PNIPAAm, PNIPAAm-b-PSBMA, and PSBMA suspension in human blood. Human fibrinogen adsorption onto the PNIPAAm-b-PSBMA copolymers from single-protein solutions was measured by DLS to determine the nonfouling stability of copolymer suspension. The new nonfouling nature of PNIPAAm-b-PSBMA copolymers was demonstrated to show extremely high anticoagulant activity and antihemolytic activity in human blood over a wide range of explored temperatures from 4 to 40 °C. The temperature-independent blood compatibility of nonionic/zwitterionic block copolymer along with their schizophrenic phase behavior in aqueous solution suggests their potential in blood-contacting applications.     

Galactosylated N-2-hydroxypropyl methacrylamide-b-N-3-guanidinopropyl methacrylamide block copolymers as hepatocyte-targeting gene carriers

As alternatives of viral and cationic lipid gene carriers, cationic polymer-based vectors may provide flexible chemistry for the attachment of targeting moieties. In this report, galactosylated N-2-hydroxypropyl methacrylamide-b-N-3-guanidinopropyl methacrylamide block copolymers (galactosylated HPMA-b-GPMA block copolymers, or abbreviated as GHG) were prepared in order to develop hepatocyte targeting gene transfection carriers. The block copolymers were synthesized by aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization of N-2-hydroxypropyl methacrylamide (HPMA) and N-3-aminopropyl methacrylamide (APMA), followed by galactosylation and guanidinylation. The molecular weight of GHG copolymers determined by static light scattering method was in the range from 48?600 to 76?240 g/mol. In addition, the galactose content in the GPMA block in the copolymers was determined to be 6.5-8.0 mol % according to the sulfuric acid method. The GHG copolymers complexed completely with plasmid DNA (pDNA) to show positive zeta-potential values with diameter 100-250 nm from charge ratio of 4, which demonstrated the excellent DNA condensing ability of guanidino groups. Furthermore, the MTT assay data of GHG/pDNA complexes on HepG2 cells and HeLa cells indicated that GHG copolymers had significantly lower cytotoxicity than PEI. In addition, the copolymers with GPMA component from 30.23% showed higher transfection efficiency than PEI at charge ratio of 12 in HepG2 cells. The result revealed that the conjugation of galactose groups in the copolymers brought asialoglycoprotein-receptor (ASGP-R) mediated transfection. The employing of HPMA component decreased the aggregation of protein in transfection presence of serum. The GHG copolymers combined the advantages of galactose moieties, guanidino groups, and HPMA component might show potential in safe hepatocyte targeting gene therapy.     

Thermoreversible hydrogels from RAFT-synthesized BAB triblock copolymers: steps toward biomimetic matrices for tissue regeneration

Narrowly dispersed, temperature-responsive BAB block copolymers capable of forming physical gels under physiological conditions were synthesized via aqueous reversible addition fragmentation chain transfer (RAFT) polymerization. The use of a difunctional trithiocarbonate facilitates the two-step synthesis of BAB copolymers with symmetrical outer blocks. The outer B blocks of the triblock copolymers consist of poly(N-isopropylacrylamide) (PNIPAM) and the inner A block consists of poly(N,N-dimethylacrylamide). The copolymers form reversible physical gels above the phase transition temperature of PNIPAM at concentrations as low as 7.5 wt % copolymer. Mechanical properties similar to collagen, a naturally occurring polypeptide used as a three-dimensional in vitro cell growth scaffold, have been achieved. Herein, we report the mechanical properties of the gels as a function of solvent, polymer concentration, and inner block length. Structural information about the gels was obtained through pulsed field gradient NMR experiments and confocal microscopy.     

Selective enzymatic degradation of self-assembled particles from amphiphilic block copolymers obtained by the combination of N-carboxyanhydride and nitroxide-mediated polymerization

Combining controlled radical polymerizations and a controlled polypeptide synthetic technique, such as N-carboxyanhydride (NCA) ring-opening polymerization, enables the generation of well-defined block copolymers to be easily accessible. Here we combine NCA polymerization with the nitroxide-mediated radical polymerization of poly(n-butyl acrylate) (PBA) and polystyrene (PS), using a TIPNO and SG1-based bifunctional initiator to create a hybrid block copolymer. The polypeptide block consists of (block) copolymers of poly(L-glutamic acid) embedded with various quantities of L-alanine. The formed superstructures (vesicles and micelles) of the block copolymers possessed varying degrees of enzyme responsiveness when exposed to elastase and thermolysin, resulting in controlled enzymatic degradation dictated by the polypeptide composition. The PBA containing block copolymers possessing 50% L-alanine in the polypeptide block showed a high degradation response compared to polymers containing lower L-alanine quantities. The particles stabilized by copolypeptides with L-alanine near the hydrophobic block showed full degradation within 4 days. Particles containing polystyrene blocks revealed no appreciable degradation under the same conditions, highlighting the specificity of the system and the importance of synthetic polymer selection. However, when the degradation temperature was increased to 70 °C, degradation could be achieved due to the higher block copolymer exchange between the particle and the solution. A number of novel biohybrid structures are disclosed that show promise as enzyme-responsive materials with potential use as payload release vehicles, following their controlled degradation by specific, target, enzymes.     

Evaluation of acrylate-based block copolymers prepared by atom transfer radical polymerization as matrices for paclitaxel delivery from coronary stents

Acrylate-based block copolymers, synthesized by atom transfer radical polymerization (ATRP) processes, were evaluated as drug delivery matrices for the controlled release of paclitaxel from coronary stents. The polymers were multiblock copolymers consisting of poly(butyl acrylate) or poly(lauryl acrylate) soft blocks and hard blocks composed of poly(methyl methacrylate), poly(isobornyl acrylate), or poly(styrene) homo- or copolymers. Depending on the ratio of hard to soft blocks in the copolymers, coating formulations were produced that possessed variable elastomeric properties, resulting in stent coatings that maintained their integrity when assessed by scanning electron microscopy (SEM) imaging of overexpanded stents. In vitro paclitaxel release kinetics from coronary stents coated with these copolymers typically showed an early burst followed by sustained release behavior, which permitted the elution of the majority of the paclitaxel over a 10-day time period. It was determined that neither the nature of the polyacrylate (n-butyl or lauryl) nor that of the hard block appeared to affect the release kinetics of paclitaxel at a loading of 25% drug by weight, whereas some effects were observed at lower drug loading levels. Differential scanning calorimetry (DSC) analysis indicated that the paclitaxel was at least partially miscible with the poly(n-butyl acrylate) phase of those block copolymers. The copolymers were also evaluated for sterilization stability by exposing both the copolymer alone and copolymer/paclitaxel coated stents to e-beam radiation at doses of 1-3 times the nominal dose used for medical device sterilization (25 kGy). It was found that the copolymers containing blocks bearing quaternary carbons within the polymer backbone were less stable to the radiation and showed a decrease in molecular weight as determined by gel-permeation chromatography. Conversely, those without quaternary carbons showed no significant change in molecular weight when exposed to 3 times the standard radiation dose. There was no significant change in drug release profile from any of the acrylate-based copolymers after exposure to 75 kGy of e-beam radiation, and this was attributed to the inherent radiation stability of the poly(n-butyl acrylate) center block.     

Resilient bioresorbable copolymers based on trimethylene carbonate, L-lactide, and 1,5-dioxepan-2-one

The new combinations of monomers presented in this work were evaluated in order to create an elastic material for potential application in soft tissue engineering. Thermoplastic elastomers (TPE) of trimethylene carbonate (TMC) with L-lactide (LLA) and 1,5-dioxepan-2-one (DXO) have been synthesized using a cyclic five-membered tin alkoxide initiator. The block copolymers were designed in such a way that poly(trimethylene carbonate-co-1,5-dioxepan-2-one) formed an amorphous middle block and the poly(L-lactide) (PLLA) formed semicrystalline terminal blocks. The amorphous middle block consisted of relatively randomly distributed TMC and DXO monomer units, and the defined block structure of the PLLA terminal segments was confirmed by 13C NMR. The properties of the TMC-DXO-LLA copolymers were compared with those of triblock copolymers based either on LLA-TMC or on LLA-DXO. Differential scanning calorimetry and dynamic mechanical analysis data confirmed the micro-phase separation in the copolymers. The mechanical properties of the copolymers were evaluated using tensile testing and cycling loading. All of the copolymers synthesized showed a highly elastic behavior. The properties of copolymers could be tailored by altering the proportions of the different monomers.     

Block versus random amphiphilic copolymers as antibacterial agents

We examined the antibacterial and hemolytic activities in a series of amphiphilic block and random copolymers of poly(vinyl ether) derivatives prepared by base-assisting living cationic polymerization. Block and random amphiphilic copolymers with similar monomer compositions showed the same level of activity against Escherichia coli . However, the block copolymers are much less hemolytic compared to the highly hemolytic random copolymers. These results indicate that the amphiphilic copolymer structure is a key determinant of activity. Furthermore, the block copolymers induced dye leakage from lipid vesicles consisting of E. coli -type lipids, but not mammalian lipids, while the random copolymers disrupted both types of vesicles. In addition, both copolymers displayed bactericidal and hemolytic activities at concentrations 1 or 2 orders of magnitude lower than their critical (intermolecular) aggregation concentrations (CACs), as determined by light scattering measurements. This suggests that polymer aggregation or macromolecular assembly is not a requisite for the antibacterial activity and selectivity against bacteria over human red blood cells (RBCs). We speculate that different single-chain conformations between the block and random copolymers play an important role in the antibacterial action and underlying antibacterial mechanisms.     

Self-assembled micelles of biodegradable triblock copolymers based on poly(ethyl ethylene phosphate) and poly(-caprolactone) as drug carriers

A series of novel amphiphilic triblock copolymers of poly(ethyl ethylene phosphate) and poly(-caprolactone) (PEEP-PCL-PEEP) with various PEEP and PCL block lengths were synthesized and characterized. These triblock copolymers formed micelles composed of a hydrophobic core of poly(-caprolactone) (PCL) and a hydrophilic shell of poly(ethyl ethylene phosphate) (PEEP) in aqueous solution. The micelle morphology was spherical, determined by transmission electron microscopy. It was found that the size and critical micelle concentration values of the micelles depended on both hydrophobic PCL block length and PEEP hydrophilic block length. The in vitro degradation characteristics of the triblock copolymers were investigated in micellar form, showing that these copolymers were completely biodegradable under enzymatic catalysis of Pseudomonas lipase and phosphodiesterase I. These triblock copolymers were used for paclitaxel (PTX) encapsulation to demonstrate the potential in drug delivery. PTX was successfully loaded into the micelles, and the in vitro release profile was found to be correlative to the polymer composition. These biodegradable triblock copolymer micelles are potential as novel carriers for hydrophobic drug delivery.     

Synthesis of temperature-responsive heterobifunctional block copolymers of poly(ethylene glycol) and poly(N-isopropylacrylamide)

Heterobifunctional block copolymers of poly(ethylene glycol) (PEG) and poly(N-isopropylacrylamide) (PNIPAM) were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization of NIPAM using a macromolecular trithiocarbonate PEG-based chain transfer agent. The polymerization showed all the expected features of living radical polymerization and allowed the synthesis of copolymers with different lengths of the PNIPAM block. The synthesized block copolymers contained a carboxylic acid group from L-lysine at the focal point and a trithiocarbonate group at the terminus of the PNIPAM block. The trithiocarbonate functionality was converted into a thiol group and used for conjugation of biotin to the end of the PNIPAM block. The copolymers exhibited temperature-dependent association behavior in aqueous solution with a phase transition of approximately 32 degrees C. The described heterobifunctional block copolymers show promise for surface modifications with the potential for stimulus-controlled surface presentation of ligands attached to the terminus of the PNIPAM block.     

From natural products to polymeric derivatives of "eugenol": a new approach for preparation of dental composites and orthopedic bone cements

Polymers with eugenol moieties covalently bonded to the macromolecular chains were synthesized for potential application in orthopedic and dental cements. First, eugenol was functionalized with polymerizable groups. The synthetic methods employed afforded two different methacrylic derivatives, where the acrylic and eugenol moieties were either directly bonded, eugenyl methacrylate (EgMA), or separated through an oxyethylene group, ethoxyeugenyl methacrylate (EEgMA). A typical Fisher esterification reaction was used for the synthesis of EgMA and EEgMA, affording the desired monomers in 80% yields. Polymerization of each of the novel monomers, at low conversion, provided soluble polymers consisting of hydrocarbon macromolecules with pendant eugenol moieties. At high conversions only cross-linked polymers were obtained, attributed to participation of the allylic double bonds in the polymerization reaction. In addition, copolymers of each eugenol derivative with ethyl methacrylate (EMA) were prepared at low conversion, with the copolymerization reaction studied by assuming the terminal model and the reactivity ratios determined according to linear and nonlinear methods. The values obtained were r(EgMA) = 1.48, r(EMA) = 0.55 and r(EEgMA) = 1.22, r(EMA) = 0.42. High molecular weight polymers and copolymers were obtained at low conversion. Analysis of thermal properties revealed a T(g) of 95 degrees C for PEgMA and of 20 degrees C for PEEgMA and an increase in the thermal stability for the eugenol derivatives polymers and copolymers with respect to that of PEMA. Water sorption of the copolymers was found to decrease with the eugenol derivative content. Both monomers EgMA and EEgMA showed antibacterial activity against Streptococcus mutans, producing inhibition halos of 7 and 21 mm, respectively. Finally, cell culture studies revealed that the copolymers did not leach any toxic eluants and showed good cellular proliferation with respect to PEMA. This study thus indicates that the eugenyl methacrylate derivatives are potentially good candidates for dental and orthopedic cements.     

Investigating the structure-property relationship of bacterial PHA block copolymers

Mechanical testing of solvent cast films consisting of short-chain-length (SCL) polyhydroxyalkanoate (PHA) films suggested that films consisting of block copolymers retained more elasticity over time with respect to films of similar random copolymers of comparable composition. Two experimental techniques, wide angle X-ray scattering (WAXS) and uniaxial extension, were used to quantitatively investigate the structure-property relationship of bacterially synthesized PHA block copolymers of poly(3-hydroxybutyrate) (PHB) homopolymer and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) random copolymer (PHBV) segments. Uniaxial testing experiments yielded the Young's modulus, ultimate tensile strength, and the elongation until fracture of the films. Percent crystallinity was determined by deconvolution of amorphous and crystalline scattering peaks obtained from WAXS. Two PHBV films containing either 8% 3-hydroxyvalerate monomer (3HV) or 29% 3HV exhibited a quick transition to brittle behavior, decreasing to less than 20% percent elongation at fracture within a few days after annealing. Conversely, the block copolymer samples remained higher than 100% elongation at fracture a full 3 months after annealing. Because block copolymers covalently link polymers that would otherwise form thermodynamically separate phases, the rates and degrees of crystallization of the block copolymers are less than the random copolymer samples. These differences translate into materials that extend the property space of biologically synthesized SCL PHA.     

Genetic engineering of stimuli-sensitive silkelastin-like protein block copolymers

Differentially charged analogues of block copolymers containing repeating sequences from silk (GAGAGS) and elastin (GVGVP) were synthesized using genetic engineering techniques by replacing a valine residue with glutamic acid. The sensitivity to pH and temperature was examined at various polymer concentrations, ionic strengths, and polymer lengths. The polymers transitioned from soluble to precipitate state over narrow temperature ranges. The transition temperature T(t) (the temperature at which half-maximal spectrophotometric absorption was observed) increased with increasing pH up to pH 7.0 and leveled off above this value for the Glu-containing polymer (17E)(11). T(t) was independent of pH for the Val-containing polymer (17V)(11). It decreased with increasing ionic strength, polymer concentration, and polymer length for both polymers. These results suggest that by substituting charged amino acids for neutral amino acids at strategic locations in the polymer backbone and by control of the length of silkelastin-like block copolymers using genetic engineering techniques, it is possible to precisely control sensitivity to pH, temperature, and ionic strength.     

Synthesis and micellization of amphiphilic brush-coil block copolymer based on poly(epsilon-caprolactone) and PEGylated polyphosphoester

A novel biodegradable amphiphilic brush-coil block copolymer consisting of poly(epsilon-caprolactone) and PEGylated polyphosphoester was synthesized by ring opening polymerization. The composition and structure of the copolymer were characterized by 1H NMR, 13C NMR, and FT-IR, and the molecular weight and molecular weight distribution were analyzed by gel permeation chromatograph (GPC) measurements to confirm the diblock structure. These amphiphilic copolymers formed micellar structures in water, and the critical micelle concentrations (CMCs) were around 10(-3) mg/mL, which was determined using pyrene as a fluorescence probe. Transmission electron microscopy (TEM) images showed that the micelles took an approximately spherical shape with core-shell structure, which was further demonstrated by laser light scattering (LLS) technique. The degradation behavior of the polymeric micelle was also investigated in the presence of Pseudomonas lipase and characterized by GPC measurement. Such polymer micelles from brush-coil block copolymers are expected to have wide utility in the field of drug delivery.     

Synthesis, characterization, and morphology studies of biodegradable amphiphilic poly[(R)-3-hydroxybutyrate]-alt-poly(ethylene glycol) multiblock copolymers

Novel biodegradable amphiphilic alternating block copolymers based on poly[(R)-3-hydroxybutyrate] (PHB) as biodegradable and hydrophobic block and poly(ethylene glycol) (PEG) as hydrophilic block (PHB-alt-PEG) were successfully synthesized through coupling reaction. Their chemical structures have been characterized by using gel permeation chromatography, (1)H nuclear magnetic resonance, and Fourier transform infrared spectroscopy. Differential scanning calorimetry (DSC) analysis revealed that both PHB and PEG blocks in PHB-alt-PEG block copolymers can crystallize to form separate crystalline phase except in those with a short PEG block (M(n) 600) only PHB crystalline phase has been observed. However, due to the mutual interference from each other, the melting transition of both PHB and PEG crystalline phases shifted to lower temperature with lower crystallinity in comparison with corresponding pure PHB and PEG. The crystallization behavior of PHB block and PEG block has also been studied by X-ray diffraction, and the results were in good agreement with those deduced from DSC study. The surface morphologies of PHB-alt-PEG block copolymer thin films spin-coated on mica have been visualized by atomic force microscopy with tapping mode, indicating formation of laterally regular lamellar surface patterns. Static water contact angle measurement revealed that surface hydrophilicity of these spin-coated thin films increases with increasing PEG block content.     

Sweet block copolymer nanoparticles: preparation and self-assembly of fully oligosaccharide-based amphiphile

The preparation of biocompatible nanocarriers that have potential applications in the cosmetic and health industries is highly desired. The self-assembly of amphiphilic block copolymers displaying biosourced polysaccharides at the surface is one of the most promising approaches. In the continuity of our works related to the preparation of "hybrid" amphiphilic oligosaccharide-based block copolymers, we present here the design of a new generation of self-assembled nanoparticles composed entirely of oligosaccharide-based amphiphilic block co-oligomers (BCO). These systems are defined by a covalent linkage of the two saccharidic blocks through their reducing end units, resulting in a sweet "head-to-head" connection. As an example, we have prepared and studied a BCO in which the hydrophilic part is composed of a free maltoheptaosyl derivative clicked to a hydrophobic part composed of a peracetylated maltoheptaosyl derivative. This amphiphilic BCO self-assembles to form spherical micelles in water with an average diameter of 30 nm. The efficient enzymatic hydrolysis of the maltoheptaose that constitutes the shell of the micelles was followed by light scattering and colorimetric methods.     

Living ring-opening polymerization of a carbohydrate-derived lactone for the synthesis of protein-resistant biomaterials

An efficient living ring-opening polymerization (ROP) of a permethoxylated epsilon-caprolactone [(OMe)CL] catalyzed by yttrium(III) isopropoxide was developed for the synthesis of degradable protein-resistant polymers [P(OMe)CL]. The lactone monomer was efficiently prepared from a reduced sugar, D-dulcitol. Kinetic studies of the ROP revealed a linear dependence of ln[M]0/[M] on polymerization time as well as a linear correlation between the number-averaged molecular weight (M(n)) and monomer conversion; both support it is a living polymerization. A series of block copolymers of our permethoxylated lactone with epsilon-caprolactone [P(OMe)CL-b-PCL] were synthesized and fully characterized. In thermal analyses only single T(g)s were observed in all the block copolymers, suggesting that P(OMe)CL and PCL blocks are fully miscible. Finally, surface plasmon resonance (SPR) sensograms demonstrated that both P(OMe)CL and the P(OMe)CL-b-PCL block copolymers exhibit excellent resistance to fibrinogen and lysozyme.     

Epidermal growth factor-conjugated poly(ethylene glycol)-block- poly(delta-valerolactone) copolymer micelles for targeted delivery of chemotherapeutics

Epidermal growth factor (EGF)-conjugated copolymer micelles were prepared from a mixture of diblock copolymers of methoxy poly(ethylene glycol)-block-poly(delta-valerolactone) (MePEG-b-PVL) and EGF-PEG-b-PVL for targeted delivery to EGF receptor (EGFR)-overexpressing cancers. The block copolymers and functionalized block copolymers were synthesized using PEG as the macroinitiator and HCl-diethyl ether as the catalyst. The MePEG-b-PVL and the carboxyl-terminated PEG-b-PVL (HOOC-PEG-b-PVL) copolymers were found to have molecular weights of 5940 and 5900, respectively, as determined by gel permeation chromatography (GPC) analyses. The HOOC-PEG-b-PVL copolymers were then activated by N-hydroxysuccinimide and subsequently reacted with EGF to form the EGF-PEG-b-PVL copolymers. The efficiency for the conjugation of EGF to the copolymer was found to be 60.9%. A hydrophobic fluorescent probe, CM-DiI, was loaded into both the nontargeted MePEG-b-PVL micelles and the targeted EGF-conjugated PEG-b-PVL micelles. The effective mean diameters of the CMDiI-loaded nontargeted and the CMDiI-loaded targeted micelles were found to be 32 +/- 1 nm and 45 +/- 2 nm, respectively, as determined by dynamic light scattering (DLS). The zeta potentials for the nontargeted micelles (no CM-DiI-loaded), CM-DiI-loaded nontargeted micelles, and CM-DiI-loaded targeted micelles were found to be -6.5, -8.7, and - 13.5 mV, respectively. Evaluation of the in vitro release of CM-DiI from the MePEG-b-PVL micelles in phosphate buffer saline (0.01 M, pH = 7.4) containing 10% (v/v) fetal bovine serum at 37 degrees C revealed that approximately 20% of the probe was released within the first 2 h. Confocal laser scanning microscopy (CLSM) analysis revealed that the targeted micelles containing CM-DiI accumulated intracellularly in EGFR-overexpressing MDA-MB-468 breast cancer cells following a 2 h incubation period, while no detectable cell uptake was observed for the nontargeted micelles. Results obtained from the confocal images were confirmed in an independent study by measuring the intracellular CM-DiI fluorescence in cell lysate. In addition, the presence of free EGF was found to decrease the extent of uptake of the targeted micelles. Nuclear staining of the cells with Hoechst 33258 indicated that the targeted micelles mainly localized in the perinuclear region and some of the micelles were localized in the nucleus. These results demonstrate that the EGF-conjugated copolymer micelles developed in this study have potential as vehicles for targeting hydrophobic drugs to EGFR-overexpressing cancers.     

In-situ formation of biodegradable hydrogels by stereocomplexation of PEG-(PLLA)8 and PEG-(PDLA)8 star block copolymers

Eight-arm poly(ethylene glycol)-poly(L-lactide), PEG-(PLLA)(8), and poly(ethylene glycol)-poly(D-lactide), PEG-(PDLA)(8), star block copolymers were synthesized by ring-opening polymerization of either L-lactide or D-lactide at room temperature in the presence of a single-site ethylzinc complex and 8-arm PEG (M(n) = 21.8 x 10(3) or 43.5 x 10(3)) as a catalyst and initiator, respectively. High lactide conversions (>95%) and well-defined copolymers with PLLA or PDLA blocks of the desired molecular weights were obtained. Star block copolymers were water-soluble when the number of lactyl units per poly(lactide) (PLA) block did not exceed 14 and 17 for PEG21800-(PLA)(8) and PEG43500-(PLA)(8), respectively. PEG-(PLA)(8) stereocomplexed hydrogels were prepared by mixing aqueous solutions with equimolar amounts of PEG-(PLLA)(8) and PEG-(PDLA)(8) in a polymer concentration range of 5-25 w/v % for PEG21800-(PLA)(8) star block copolymers and of 6-8 w/v % for PEG43500-(PLA)(8) star block copolymers. The gelation is driven by stereocomplexation of the PLLA and PDLA blocks, as confirmed by wide-angle X-ray scattering experiments. The stereocomplexed hydrogels were stable in a range from 10 to 70 degrees C, depending on their aqueous concentration and the PLA block length. Stereocomplexed hydrogels at 10 w/v % polymer concentration showed larger hydrophilic and hydrophobic domains as compared to 10 w/v % single enantiomer solutions, as determined by cryo-TEM. Correspondingly, dynamic light scattering showed that 1 w/v % solutions containing both PEG-(PLLA)(8) and PEG-(PDLA)(8) have larger "micelles" as compared to 1 w/v % single enantiomer solutions. With increasing polymer concentration and PLLA and PDLA block length, the storage modulus of the stereocomplexed hydrogels increases and the gelation time decreases. Stereocomplexed hydrogels with high storage moduli (up to 14 kPa) could be obtained at 37 degrees C in PBS. These stereocomplexed hydrogels are promising for use in biomedical applications, including drug delivery and tissue engineering, because they are biodegradable and the in-situ formation allows for easy immobilization of drugs and cells.     

Influence of polymer structure on adsorption behavior at solid–liquid interface by Monte Carlo simulation

Monte Carlo simulations for the adsorption of polymers including random copolymer, homopolymer, diblock copolymer and two kinds of triblock copolymers, respectively, in nonselective solvent at solid–liquid interface have been performed on a simple lattice model. The effect of polymer structure on adsorption properties was examined. In simulations, all polymeric molecules are modeled as self-avoiding linear chains composed of two segments A and B while A is attractive to the surface and B is non-attractive. It was found that for all polymers, the size distribution of various configurations is determined by the linked sequence of segments and the interaction energy between segment and surface. The results of simulation show that the adsorbed amount always increases with increasing bulk concentration but the adsorption layer thickness is mostly dependent on the adsorption energy at a fixed fraction of segments A. On the other hand, diblock copolymer has always the highest surface coverage and adsorbed amount, while random copolymers and homopolymers give generally the smallest surface coverage and adsorbed amount. It is shown that the sequence of polymer chains, i.e. molecular structure, is the most important factor in affecting adsorption properties at the same composition and interaction between segment and surface. The results also show that the adsorption behavior of random copolymers is remarkably different from that of block copolymers, but acting like homopolymer.     

Functionalized micellar assemblies prepared via block copolymers synthesized by living free radical polymerization upon peptide-loaded resins

Hybrid peptidic-synthetic amphiphilic block copolymers, synthesized by living free radical polymerization (LFRP) on solid support, have been utilized as precursors for nanoscale materials possessing bio-available peptides. LFRP initiators, coupled to the peptide terminus upon the resin, facilitated the growth of homo- and block copolymers via nitroxide mediated radical polymerization (NMRP) or atom transfer radical polymerization (ATRP). Herein, the versatile solid-support synthesis of the antimicrobial peptide tritrpticin, coupling of living free radical polymerization initiators to the peptide-loaded resin, and the controlled radical polymerization of various monomers to yield amphiphilic diblock copolymers are described. Assembly of the peptidic-synthetic block copolymers into micelles and a preliminary assessment of their in vitro biological properties are detailed.