Synthesis of nanoparticles based on PDMMLA derivative copolymers and study of warfarin encapsulation and controlled release

Abstract

Poly((R,S)-3,3-dimethylmalic acid) (PDMMLA) copolymers were synthesized by anionic ring opening polymerization of benzylic and hexylic lactones. The PDMMLA copolymer family has biodegradable and biocompatible properties of interest as nanoparticles (NPs) can be formed from PDMMLA derivatives. For this purpose, three statistical copolymers (PDMMLAH₃₀-co-Hex₇₀, PDMMLAH₅₀-co-Hex₅₀ and PDMMLAH₇₀-co-Hex₃₀) and three block copolymers (PDMMLAH₃₀-b-Hex₇₀, PDMMLAH₅₀-b-Hex₅₀ and PDMMLAH₇₀-co-Hex₃₀) were synthesized and characterized. The main objective of the present study was to formulate new PDMMLA derivative NPs with defined size and shape that can efficiently be used as a novel controlled delivery system for a hydrophobic antithrombotic drug: warfarin. Polymeric NPs were prepared by nanoprecipitation method, optimized and characterized by Transmission Electronic Microscopy (TEM) for morphology investigation and Dynamic Light Scattering (DLS) for size and surface charge analysis. Controlled release of the drug is followed by reverse phase High Performance Liquid Chromatography (HPLC) for four weeks in phosphate buffer at pH = 7.4.