Preparation of Copolymer Paclitaxel Covalently Linked via a Disulfide Bond and Its Application on Controlled Drug Delivery

Abstract

A novel controlled drug delivery system based on copolymer covalently linked paclitaxel via a disulfide bond was constructed. Copolymer with poly(ethylene glycol) (PEG) side chains and carboxyl groups on the backbone was prepared by radical copolymerization of tert-butyl acrylate and poly(ethylene glycol) methyl ether acrylate, followed by selectively hydrolyzing tert-butyl groups to carboxyl groups. Utilizing the carboxyl group as an active reaction site, paclitaxel, a well-known chemotherapeutic drug, could be covalently linked to the backbone of a copolymer via a disulfide bond, and the loading content of paclitaxel could reach up to 32 wt %. In aqueous solution, this drug-loaded copolymer could self-assemble into a spherical micelle, with the hydrophobic drug as the core and hydrophilic PEG as the shell. The mean diameter of the micelles evaluated by transmission electron microscopy (TEM) and dynamic light scattering (DLS) was approximately 60 nm. The in vitro cytotoxicity experiments showed that the copolymer was biocompatible and suitable to use as a drug carrier. After covalently loading the drug, the copolymer showed apparent cytotoxicity to OS-RC-2 cells (kidney tumor cells) and low cytotoxicity to macrophage cells (human normal cells), indicating that the disulfide bond was stable in human normal cells, but would be broken in tumor cells. This selective bond scission behavior is potentially favorable for reducing the toxic and side effects of chemotherapeutic drugs.