title: Polymerizable disulfide paclitaxel prodrug for controlled drug delivery.
abstract: A polymerizable disulfide paclitaxel (PTX) prodrug was synthesized by the consequential esterification reactions of 3,3'-dithiodipropionic acid (DTPA), a disulfide compound containing two active carboxyl groups, with 2-hydroxyethyl methacrylate (HEMA) and PTX. The structure of the prodrug was confirmed by (1)H NMR characterization. Then, the polymerizable prodrug was copolymerized with poly(ethylene glycol) methyl ether methacrylate (PEGMEA) to obtain a copolymer with hydrophilic PEG side chains and PTX covalently linked onto the backbone via disulfide bonds. The loading content of PTX was 23%. In aqueous solution, this copolymer prodrug could self-assemble into micelles, with hydrophobic PTX as the cores and hydrophilic PEG-segment as the shells. In vitro cell assay demonstrated that this copolymer prodrug showed more apparent cytotoxicity to cancer cells than to human normal cells. After incubation for 48 h, the cell viability of HEK-293 cells (human embryo kidney cells) at 0.1 μg/mL PTX still remained more than 90%, however, that of HeLa cells (human cervical cancer cells) decreased to 52%.
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, China.
authors.forename: Wulian
authors.initials: W
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, China; Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA (Fudan University), Shanghai 201203, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Hu
authors.affiliation: Medical Center for Diagnostics & Treat of Cervical Disease, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China. Electronic address: mutudu@gmail.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Du
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, China. Electronic address: yangdong@fudan.edu.cn.
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations; D004220:Disulfides / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008689:Methacrylates / Q000737:chemistry; D008823:Micelles; D017239:Paclitaxel / Q000737:chemistry* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry; D058105:Polymerization; D011108:Polymers / Q000737:chemistry; D011355:Prodrugs / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D003692:Delayed-Action Preparations; D004220:Disulfides; D004337:Drug Carriers; D008689:Methacrylates; D008823:Micelles; D011108:Polymers; D011355:Prodrugs; C524499:polyethylene glycol methacrylate; D011092:Polyethylene Glycols; C005044:hydroxyethyl methacrylate; D017239:Paclitaxel
keywords: Controlled drug delivery; Disulfide bond; Paclitaxel; Polymerizable prodrug