Study on the synthesis of biodegradable MPEG-b-P(L-lactide-co-ε-caprolactone) and their release behavior as nanoparticles

Abstract

The aim of the research in this thesis is to synthesize novel amphiphilic biodegradable polymers for biomedical application and investigate their potential use as an anticancer drug delivery carrier. DDS (drug delivery systems) based on polyester have been much investigated due to their biodegradability, biocompatibility and nontoxicity. There are still many problems to be resolved such as cell deformation and denaturation of the loading materials. In this study, we prepared novel diblock copolymer based on the MPEG and random copolymers of L-lactide and ε-caprolactone with different feed weight composition ratios by solution polymerization. MPEG-b-P($_{L}LA$-co-$_{ε}CL$) copolymers with various compositions were synthesized by solution polymerization using stannous octoate as a catalyst. The product copolymers were characterized by DSC, $_1H NMR$, $_13C NMR$, FT-IR, and WAXS analysis. The degree of hydrophilicity of the diblock copolymer was determined by the water uptake test and water contact angle measurement. Diblock copolymers comprising randomized $_{L}LA$ and $_{ε}CL$ segments as well as PEG units showed rather a lower crystallinity and a higher hydrophilicity than the conventional block copolymer based on the $_{L}LA$ and $_{ε}CL$. MPEG-b-P($_{L}LA$-co-$_{ε}CL$) copolymer containing equal amount of randomized $_{L}LA$ and $_{ε}CL$ units was found to be most effective in the reduction of crystallinity and in the enhancement of hydrophilicity. Sythesized polyester copolymers with and without PEGME chains were used as preparing nanoparticles with spironolactone though a spontaneous emulsification and solvent diffusion method both to reduce the size down the submicron range and to fabricate the high efficient drug carrier. MPEG-b-P($_{L}LA$-co-$_{ε}CL$) with various composition and P($_{L}LA$-ran-$_{ε}CL$) nanoparticles were characterized via. tools of DLS, zeta potential, XPS, and HPLC analysis. PEGME chains located on the particle surface could endow...