Poly(L-lactide)-Poly(ethylene glycol) Multiblock Copolymers: Synthesis and Properties

Poly (L-lactide)-poly(ethylene glycol) multiblock copolymers with predetermined block lengths were synthesized by polycondensation of PLA diols and PEG diacids. These copolymers presented special properties, such as better miscibility between the two components, low crystallinity and better hydrophilicity, which can be modulated by adjusting the block lengths of the two components.

Preparation and characterization of biodegradable nanoparticles from methoxy poly(ethylene glycol)-poly(D,L-lactide)block copolymers as novel drug carriers

Methoxy poly(ethylene glycol)-poly(D,L-lactide) block copolymers (PEG-PLA) were prepared through ring-opening polymerization.The oil in water suspension method was used to prepare block copolymer micelles. The critical micelle concentration (CMC) by fluorescence spectroscopy was 0.0056 mg·ml -1 . The physical state of the inner core region of micelles was characterized with 1HNMR. The size of indomethacin (IMC) loaded micelles measured by dynamic light scattering (DLS) showed narrow monodisperse size distribution and the average diameters were less than 50 nm. In addition, the nanoparticles with relatively high drug loading content (DLC) were obtained.

Selective swelling of polysulfone/poly(ethylene glycol) block copolymer towards fouling-resistant ultrafiltration membranes

Fouling resistance of ultrafiltration(UF) membranes is critical for their long-term usages in terms of stable performance, so convenient approaches to prepare fouling-resistant membranes are always anticipated. Herein, we demonstrate the facile fabrication of antifouling polysulfone-block-poly(ethylene glycol)(PSF-b-PEG, SFEG)composite membranes. SFEG layer was coated onto macroporous supports and cavitated by immerging them in acetone/n-propanol following the mechanism of selective swelling induced pore generation. Thus-produced SFEG membranes possessed high permeance and excellent mechanical strength. Meanwhile, the structures and separation performances of the SFEG layers can be continuously tuned through simply changing swelling durations. More importantly, the hydrophilic PEG chains were spontaneously enriched onto the pore walls through swelling treatment, endowing intrinsic antifouling property to the SFEG membranes. Bovine serum albumin(BSA)/humic acid(HA) fouling tests proved the prominent fouling resistance of SFEG membranes, and the fouling resistance is expected to be long-standing because of the firm connection between PEG chains and PSF matrix by covalent bonding.

Y-shaped block copolymers of poly(ethylene glycol) and poly(N-isopropylacrylamide) synthesized by ATRP

Novel Y-shaped block copolymers of poly（ethylene glycol） and poly（N-isopropylacrylamide）, PEG-b-（PNIPAM）2, were successfully synthesized through atom transfer radical polymerization （ATRP）. A difunctional macroinitiator was prepared by esterification of 2,2-dichloroacetyl chloride with poly（ethylene glycol） monomethyl ether （PEG）. The copolymers were obtained via the ATRP ofN-isopropylacrylamide （NIPAM） at 30℃ with CuCl/Me6TREN as a catalyst system and DMF/H2O （v/v = 3：1） mixture as solvent. The resulting copolymers were characterized by gel permeation chromatography （GPC） and ^1H NMR. These block copolymers show controllable molecular weights and narrow molecular weight distributions （PDI 〈 1.15）. Their phase transition temperatures and the corresponding enthalpy changes in aqueous solution were measured by differential scanning calorimetry （DSC）. As a result, the phase transition temperature of PEG45-b-（PNIPAM55）2 is higher than that of PNIPAM, however, the corresponding enthalpy change is much lower, indicating the significant influence of the macromolecular composition and architecture on the phase transition.

PREPARATION OF HIGH DENSITY POLYETHYLENE/POLYETHYLENE-BLOCK-POLY(ETHYLENE GLYCOL)COPOLYMER BLEND POROUS MEMBRANES VIA THERMALLY INDUCED PHASE SEPARATION PROCESS AND THEIR PROPERTIES

High density polyethylene （HDPE）/polyethylene-block-poly（ethylene glycol） （PE-b-PEG） blend porous membranes were prepared via thermally induced phase separation （TIPS） process using diphenyl ether （DPE） as diluent. The phase diagrams of HDPE/PE-b-PEG/DPE systems were determined by optical microscopy and differential scanning calorimetry （DSC）. By varying the content of PE-b-PEG, the effects of PE-b-PEG copolymer on morphology and crystalline structure of membranes were studied by scanning electron microscopy （SEM） and wide angle X-ray diffraction （WAXD）. The chemical compositions of whole membranes and surface layers were characterized by elementary analysis, Fourier transform infrared spectroscopy-attenuated total reflection （FTIR-ATR） and X-ray photoelectron spectroscopy （XPS）. Water contact angle, static protein adsorption and water flux experiments were used to evaluate the hydrophilicity, antifouling and water permeation properties of the membranes. It was found that the addition of PE-b-PEG increased the pore size of the obtained blend membranes. In the investigated range of PE-b-PEG content, the PEG blocks could not aggregate into obviously separated domains in membrane matrix. More importantly, PE-b-PEG could not only be retained stably in the membrane matrix during membrane formation, but also enrich at the membrane surface layer. Such stability and surface enrichment of PE-b-PEG endowed the blend membranes with improved hydrophilicity, protein absorption resistance and water permeation properties, which would be substantially beneficial to HDPE membranes for water treatment application.

POLYCAPROLACTONE-POLY (ETHYLENE GLYCOL) BLOCK COPOLYMER Ⅲ DRUG RELEASE BEHAVIOR

The drug release behavior of degradable polymer--polycaprolactone-poly (ethyleneglycol)block copolymer(PCE) in vitro was investigated by using 5-Fluoro-uracil (5-Fu) asa model drug under a condition of pH 7. 4 at 37C. It is found that the release rate of 5-Fufrom PCE increased with increasing polyether content of the copolymer. The results showthat the increasing polyether content of the copolymer caused increasing hydrophilicity anddecreasing crystallinity of the PCE copolymer. Thus, the drug release behavior and thedegradable property of the PCE can be controlled by adjusting the composition of thecopolymer.

SYNTHESIS OF NOVEL BLOCK COPOLYMERS OF POLY(3-HYDROXYBUTYRIC ACID)WITH POLY(ETHYLENE GLYCOL)THROUGH ANIONIC POLYMERISATION

A novel kind of copolymer with ABA-type block structure was synthesized by anionic ring-opening polymerization of beta-butyrolactone (beta-BL) in the presence of a PEG-based dicarboxylates as macroinitiators which were prepared by the esterification of aliphatic cyclic anhydride and poly(ethylene glycol) (PEG) oligomers (M-n = 2000, 4000 and 6000) and conversion of potassium dicarboxylates. The resultant copolymers as well as the intermediates were characterized by IR, H-1-NMR and GPC.

Enzymatic Synthesis and Characterization of Novel Amphiphilic Triblock Copolymer Poly(p-dioxanone-co-5-benzyloxytrimethylene carbonate)-block-poly(ethylene glycol)

Novel amphiphilic triblock copolymer poly（p-dioxanone-co-5-benzyloxytrimethylene carbonate）-block-poly（ethylene glycol）-block-poly（p-dioxanone-co-5-benzyloxytrimethylene carbonate） （p（PDO-co-BTMC）-b-PEG-b-p（PDO-co-BTMC）） was successfully synthesized using immobilized porcine pancreas lipase on porous silica particles （IPPL） as the catalyst for the fLrSt time. 1H NMR, 13C NMR and GPC analysis were used to confirm the structures of resulting copolymers. The molecular weight （Mn） of the copolymer with feed ratio of 69：20：11 （BTMC： PDO： PEG ） was 31300 g/mol and the polydispersity was 1.85, while the Mn decreased to 25000 g/mol and polydispersity of 1.93 with the feed ratio of 50：40：10.

Preparation and Characterization of Copolymer Micelles Formed by Poly(ethylene glycol)-Polylactide Block Copolymers as Novel Drug Carriers

Diblock copolymer poly(ethylene glycol) methyl ether–polylactide (MePEG–PLA) micelles were prepared by dialysis against water. Indomethacin (IMC) as a model drug was entrapped into the micelles by dialysis method. The critical micelle concentration (CMC) of the prepared micelles in distilled water investigated by fluorescence spectroscopy was 0.0051 mg/mL which is lower than that of common low molecular weight surfactants. The diameters of MePEGPLA micelles and IMC loaded MePEGPLA micelles in a number-averaged scale measured by dynamic light scattering were 52.4 and 53.7 nm respectively. The observation with transmission electron microscope and scanning electron microscope showed that the appearance of MePEGPLA micelles was in a spherical shape. The content of IMC incorporated in the core portion of the micelles was 18% (ω). The effects of the synthesis method of the copolymer on the polydispersity of the micelles and the yield of the micelles formation were discussed.

SYNTHESIS OF POLY(ETHYLENE TEREPHTHALATE)-POLYCAPROLACTONE BLOCK COPOLYMER BY DIRECT COPOLYMERIZATION

Po ly(ethylene terephthalate)-polycaprolactone block copolymer (PCL-b-PET) is a polyester with improved biodegradability. In the present paper, a new direct copolymerization method of epsilon-caprolactone (epsilon-CL) and bishydroxyethylene terephthalate (BHET) in the presence of Ti(OBu)(4) was proposed for the synthesis of PCL-b-PET. The PCL-b-PET copolymer was characterized by IR, GPC and H-1-NMR techniques, and the effects of synthesis conditions, such as temperature, reaction time and concentration of catalyst on the copolymerization were discussed.

POLYMERIZATION OF ETHYLENE METHYL PHOSPHATE IN THE PRESENCE OF SODIUM POLY(ETHYLENE GLYCOL)ATE

Poly(ethylene methyl phosphate)-poly(ethylene glycol)-poly(ethylene methyl phosphate) triblock copolymers carrying hydroxyl group at both chain ends were synthesized with sodium poly(ethylene glycol)ate as initiator. The effects of the factors such as solvent, amount of the initiator and reaction time were investigated. The copolymers were characterized by IR, H-1-NMR, H-1{P-31}-NMR, C-13-NMR, P-31{H-1}-NMR, and DSC. High molecular weight of the copolymer and high yield of the polymerization were achieved within 3 min at 25 degrees C. The polymerization process was studied by P-31{H-1}-NMR and transesterification was found during longer polymerization time.

The Synthesis of Poly(ethylene oxide)-Block-Polybutylacrylate

Poly(ethylene oxide) containing azogroups(pre PEO) was prepared by reacting azoisobutyronitrile (AIBN) with poly( ethylene glycol ) (PEG). The molecular weight of pre PEO was depended on the reaction time, the ratio of PEG to AIBN and the molecular weight of PEG. Pre PEO decomposed in the presence of butylacrylate (BA) monomer to form poly ethylene oxide block butylacrylate copolymers(PEO b PBA). The molecular weights of PEO b PBA and the homopolymer of PBA were proportional to the ratio of BA to pre PEO. The purified block copolymers were charactherized using IR, 1H NMR and GPC.

Block Copolymer Solid Electrolytes Based on Comb-Like Poly(ethylene glycol)Plasticized Poly(ionic liquid)s for Lithium-Ion Batteries

Electrolytes based on poly(ionic liquid)s(PILs)have attracted great attention in the fields of next-generation solid lithium-ion batteries.However,the low ionic conductivity prevents their practical applications.Herein,we report novel solid electrolytes based on block copolymers composed of PILs and comb-like poly(ethylene glycol)(PEG),which were synthesized via ring-opening metathesis polymerization of 3-(2-(bicyclo[2.2.1]hept-5-en-2-yl)ethyl)-1-butyl-1H-imidazol-3-ium bis((trifluoromethyl)sulfonyl)amide and poly(ethylene glycol monomethyl ether)bicyclo[2.2.1]hept-5-ene-2-carboxylate.Comb-like PEG acts as plasticizers in block copolymers dominated by PILs to promote the mobility of PILs segments.Effects of the copolymer composition and length of the comb-like PEG chain on ionic conductivity were investigated.The optimized electrolyte delivers the highest ionic conductivity of 1.5×10^(–5)S·cm^(–1)at 30℃,and robust electrochemical stability up to 4.6 V.A solid-state Li/LiFePO4 cell using the optimized electrolyte demonstrates good cycle performance at 0.2 C with high capacity retention of 92%after 70 cycles at 50℃.

Synthesis of poly(ethylene glycol)-SS-poly(ε-caprolactone)-SS-poly(ethylene glycol)triblock copolymers via end-group conjugation and self-assembly for reductively responsive drug delivery

In this study,we describe a simple synthesis route to prepare triblock copolymers with disulfide-linkers,poly(ethylene glycol)-SS-poly(ε-caprolactone)-SS-poly(ethylene glycol)(PEG-SS-PCL-SS-PEG)for application in the reductively responsive release of doxorubicin(DOX).To synthesize PEG-SS-PCL-SS-PEG,two end-groups of PCL-diol were first modified with cystamine to introduce disulfide bonds and subsequently conjugated with PEG-NHS via carbodiimide chemistry.PEG-SS-PCL-SSPEG fabricated into polymeric micelles with stable structure and different nanoscale sizes via adjusting the PCL chain length,showing obvious reductive responsiveness and fast drug release of encapsulated DOX in the presence of glutathione(GSH).Moreover,DOX-loaded PEG-SS-PCL-SS-PEG micelles exhibited higher therapeutic efficacy than reduction-insensitive PEG-b-PCL micelles in vitro.Thus,end-groups conjugation is a simple and straightforward strategy to introduce intelligent responsiveness in biocompatible block copolymers and improve their therapeutic efficacy.

Methoxy poly(ethylene glycol)-b-poly(ethyl cyanoacrylate) copolymer nanoparticles as delivery vehicles for dexamethasone

Methoxy poly(ethylene oxide)-b-poly(ethyl cyanoacrylate) (mPEG-b-PECA), amphiphilic block copolymer, was synthesized via oxyanion-initiated polymerization with a sodium alcoholate-terminated monomethoxy poly(ethylene glycol) as the macroinitiator. mPEG-b-PECA was characterized by GPC, 1H-NMR and FTIR. The results indicate that the structure of mPEG-b-PECA is well controlled with narrow molecular weight distribution. The dexamethasone (DXM)-loaded mPEG-b-PECA nanoparticles (NPs) were prepared by the nanoprecipitation technique and characterized by LPSA, 1H-NMR and TEM. The DXM-loaded mPEG-b-PECA NPs are of spherical shape with the size of less than 100 nm. The drug-loaded amount (DL) and encapsulation efficiency (EE) of DXM-loaded NPs were investigated by HPLC. The results show that DXM can be effectively incorporated into mPEG-b-PECA NPs, which provides a potential delivery system for DXM and other hydrophobic drugs.

Co-delivery of resveratrol and docetaxel via polymeric micelles to improve the treatment of drug-resistant tumors

Co-delivery of anti-cancer drugs is promising to improve the efficacy of cancer treatment.This study was aiming to investigate the potential of concurrent delivery of resveratrol(RES)and docetaxel(DTX)via polymeric nanocarriers to treat breast cancer.To this end,methoxyl poly(ethylene glycol)-poly(D,L-lactide)copolymer(mPEG-PDLA)was prepared and characterized using FTIR and 1H NMR,and their molecular weights were determined by GPC.Isobologram analysis and combination index calculation were performed to find the optimal ratio between RES and DTX to against human breast adenocarcinoma cell line(MCF-7 cells).Subsequently,RES and DTX were loaded in the mPEG-PDLA micelles simultaneously,and the morphology,particle size distribution,in vitro release,pharmacokinetic profiles,as well as cytotoxicity to the MCF-7 cells were characterized.IC50 of RES and DTX in MCF-7 cells were determined to be 23.0μg/ml and 10.4μg/ml,respectively,while a lower IC50 of 4.8μg/ml of the combination of RES and DTX was obtained.The combination of RES and DTX at a ratio of 1:1(w/w)generated stronger synergistic effect than other ratios in the MCF-7 cells.RES and DTX loaded mPEG-PDLA micelles exhibited prolonged release profiles,and enhanced cytotoxicity in vitro against MCF-7 cells.The AUC(0→t)of DTX and RES in mPEG-PDLA micelles after i.v.administration to rats were 3.0-fold and 1.6-fold higher than that of i.v.injections of the individual drugs.These findings indicated that the co-delivery of RES and DTX using mPEG-PDLA micelles could have better treatment of tumors.

Influence of Chain Architectures on Crystallization Behaviors of PLLA Block in PEG/PLLA Block Copolymers

The effect of the architecture of poly(ethylene glycol)/poly(L-lactide)(PEG/PLLA) block copolymers on the non-isothermal crystallization behaviors of PLLA blocks was investigated by differential scanning calorimetry(DSC) and wide angle X-ray diffraction(WAXD). 1-Arm MPEG-b-PLLA and 4-arm PEG-b-PLLA(4PEG-b-PLLA) were synthesized by the ring-opening polymerization of Llactide in the presence of poly(ethylene glycol) methyl ether(MPEG) and 4-arm poly(ethylene glycol)(4PEG). 4-Arm PLLA-b-MPEG(4PLLA-b-PEG) was synthesized by coupling 4-arm PLLA and MPEG. The WAXD results indicated that the crystalline structure of PLLA blocks did not alter due to the different chain architectures. The average values of Avrami index(ˉn) were all above 4, which indicated that the nucleation mechanism of PLLA blocks was heterogeneous nucleation, regardless of the architectures. The overall crystallization rates were decreased markedly as following: MPEG-b-PLLA > 4PEG-b-PLLA > 4PLLA-b-PEG, ascribed to the different confinement by PEG blocks and to the steric hindrance of chain architectures. Therefore, the crystallization of PLLA blocks became more difficult and the crystallization activation energy of the PLLA blocks increased due to the confinement of chain architectures.

Self-assembly of monodisperse polymer microspheres from PPQ-b-PEG rod-coil block copolymers inselective solvents

Poly(phenylquinoline)-block-poly(ethylene glycol)(PPQ-b-PEG) rod-coil block co- polymers possess the self-assembly behavior in selective solvents. The copolymers in the mixed solvents of V(trifluoroacetic acid, TFA)︰V(dichloromethane, DCM)=1︰1 can self-assemble into polymer hollow microspheres with diameters of a few micrometers. The polymer hollow micro- spheres are monodisperse, and the diameters of them increase with an increased polymerization degree of the PPQ rigid-rod block. The solution concentration has no effect on the microsphere diameter, but spherical surface shows burrs when the solution concentration is too low. It has been found that the obtained dilute solution has the strongest absorption peak at 376 nm and strongest emissionpeak at 604 nm by the spectroscopy analysis.

三嵌段共聚物临界胶束浓度与分子横截面积测定

采用双毛细管最大泡压法装置测定了25℃条件下不同浓度非离子表面活性剂聚乙二醇-聚丙二醇-聚乙二醇三嵌段共聚物(PEG-PPG-PEG;Pluronic L-64)对溶液表面张力的影响。采用Origin软件对数据进行处理分析,计算得到其临界胶束浓度(CMC)。基于吉布斯(Gibbs)与朗格缪尔(Langmuir)吸附等温式,对溶液表面张力与浓度关系进行一步非线性拟合,计算获得吸附分子的横截面积。该实验扩展了最大泡压法测定表面张力的应用,提高了学生分析处理实验数据的能力。

IMPROVING THE PROPERTIES OF HDPE BASED SEPARATORS FOR LITHIUM ION BATTERIES BY BLENDING BLOCK WITH COPOLYMER PE-b-PEG

To improve the performances of HDPE-based separators, polyether chains were incorporated into HDPE membranes by blending with poly（ethylene-block-ethylene glycol） （PE-b-PEG） via thermally induced phase separation （TIPS） process. By measuring the composition, morphology, crystallinity, ion conductivity, etc, the influence of PE-b-PEG on structures and properties of the blend separator were investigated. It was found that the incorporated PEG chains yielded higher surface energy for HDPE separator and improved affinity to liquid electrolyte. Thus, the stability of liquid electrolyte trapped in separator was increased while the interfacial resistance between separator and electrode was reduced effectively. The ionic conductivity of liquid electrolyte soaked separator could reach 1.28 ×10^-3 S.cm^-1 at 25℃, and the electrochemical stability window was up to 4.5 V （versus Li^＋/Li）. These results revealed that blending PE-b-PEG into porous HDPE membranes could efficiently improve the performances of PE separators for lithium batteries.