Preparation of Amphiphilic Copolymers for Covalent Loading of Paclitaxel for Drug Delivery System

摘要

A novel drug-polymer conjugate was prepared by the copper-catalyzed azide-alkyne cycloaddition reaction between an azide-functional diblock copolymer and an alkynefunctional paclitaxel (PTX). The well-defined azide-functional diblock copolymer, poly(ethylene glycol) (PEG)-b-P(OEGEEMAco- AzPMA), was synthesized via the atom transfer radical polymerization of oligo(ethylene glycol) ethyl ether methacrylate (OEGEEMA) and 3-azidopropyl methacrylate (AzPMA), using PEG-Br as macroinitiator and CuBr/PMDETA as a catalytic system. The alkyne-functional PTX was covalently linked to the copolymer via a click reaction, and the loading content of PTX could be easily tuned by varying the feeding ratio. Transmission electron microscopy and dynamic light scattering results indicated that the drug loaded copolymers could self-assemble into micelles in aqueous solution. Moreover, the drug release behavior of PEG-b-P(OEGEEMA-co-AzPMA-PTX) was pH dependent, and the cumulative release amount of PTX were 50.0% at pH 5.5, which is about two times higher than that at pH 7.4. The in vitro cytotoxicity experimental results showed that the diblock copolymer was biocompatible, with no obvious cytotoxicity, whereas the PTX-polymer conjugate could efficiently deliver PTX into HeLa and SKOV-3 cells, leading to excellent antitumor activity.