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.

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.