Degradable and biocompatible aldehyde-functionalized glycopolymer conjugated with doxorubicinvia acid-labile Schiff base linkage for pH-triggered drug release

Abstract

Well-defined aldehyde-functionalized glycopolymers were synthesized via reversible addition-fragmentation chain transfer (RAFT) copolymerization of 1,2:3,4-di-O-isopropylidene-6-O-(2′-formyl-4′-vinylphenyl)-D-galactopyranose (IVDG) and 5,6-benzo-2-methylene-1,3-dioxepane (BMDO) using dicumyl peroxide as the initiator and 1-phenylethyl phenyldithioacetate as the RAFT agent at 130 °C in anisole. The resulting copolymers were found to be hydrolytically degradable due to their main-chain polyester structures. Removal of the protective isopropylidene groups from the sugar residues resulted in a novel amphiphilic copolymer with low cytotoxicity as confirmed by MTT assay against L929 cells. The deprotected copolymer could conjugate anticancer drug DOXvia an acid-labile Schiff base linkage to form DOX-loaded micelles in a high drug loading level (∼14 wt%) with pendent galactose moieties covering the surface. The size of the DOX-conjugated polymeric micelle was determined to be about 125 nm by dynamic light scattering. The in vitro release studies demonstrated that the release of DOX from the micelles manifested a strong dependence on the environment pH due to the acid-cleavable Schiff base linkage between the DOX and micelles. The DOX release was significantly faster at pH 5.0 compared to pH 7.4.