title: 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.
authors: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, P. R. China.
authors: Wulian
authors: W
authors: Chen
authors: Yuanlin
authors: Y
authors: Shi
authors: Hua
authors: H
authors: Feng
authors: Ming
authors: M
authors: Du
authors: Jin Zhong
authors: JZ
authors: Zhang
authors: Jianhua
authors: J
authors: Hu
authors: Dong
authors: D
authors: Yang
mesh_terms: D000179:Acrylates / Q000737:chemistry; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004220:Disulfides / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D008689:Methacrylates / Q000737:chemistry; D017239:Paclitaxel / Q000737:chemistry* / Q000633:toxicity; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011109:Polymethacrylic Acids
chemical_list: D000179:Acrylates; D000972:Antineoplastic Agents, Phytogenic; D004220:Disulfides; D004337:Drug Carriers; D008689:Methacrylates; D011108:Polymers; D011109:Polymethacrylic Acids; C528061:poly(poly(ethylene glycol)methacrylate); D011092:Polyethylene Glycols; C522411:tert-butyl acrylate; D017239:Paclitaxel