Novel amphiphilic, biodegradable, biocompatible, cross-linkable copolymers: synthesis, characterization and drug delivery applications

Abstract

The synthesis of a new kind of amphiphilic poly(vinyl-co-ester)s via simple one-pot radical ring-opening polymerization (RROP) is reported. A series of biodegradable, biocompatible, and cross-linkable copolymers P(MDO-co-PEGMA-co-CMA) with different compositions were synthesized by copolymerization of 2-methylene-1,3-dioxepane (MDO), poly(ethylene glycol) methyl ether methacrylate (PEGMA) and 7-(2-methacryloyloxyethoxy)-4-methylcoumarin methacrylate (CMA). All the copolymers were well characterized by ¹H NMR, ¹³C NMR, and gel permeation chromatography (GPC). The hydrolytic degradation and enzymatic degradation of the copolymers were investigated. The amphiphilic P(MDO-co-PEGMA-co-CMA) can self-assemble into micelles in aqueous solution. Polymeric micelles with different sizes were obtained through tuning the compositions of the copolymers, i.e., the hydrophilic/hydrophobic ratio. The size and morphology of the micelles were measured by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Because of the coumarin side groups in the micellar core, the micelles can be cross-linked upon exposure to long-wavelength UV light (λ = 365 nm). These micelles also showed excellent biocompatibility by the in vitro cytotoxicity experiments. Furthermore, the biodegradable micelles were applied for the delivery of an anticancer drug doxorubicin (DOX). The cell viability of DOX-loading micelles compared to free DOX was discussed. The effects of cross-linking and the copolymer composition on the drug release behavior were well studied. The results indicate that this new kind of amphiphilic poly(vinyl-co-ester)s could serve as promising nanocarriers for the delivery of anticancer drugs.