title: Thymine-functionalized amphiphilic biodegradable copolymers for high-efficiency loading and controlled release of methotrexate.
abstract: In this study, a novel thymine-functionalized six-membered cyclic carbonate monomer (TAC) was synthesized by the Michael-addition reaction between thymine and acryloyl carbonate (AC). The corresponding functional amphiphilic block copolymer mPEG-b-PTAC was further successfully synthesized by ring-opening polymerization using immobilized porcine pancreas lipase (IPPL) as the catalyst and mPEG as the macroinitiator. Meanwhile, mPEG-b-P(TAC-co-DTC) and mPEG-b-PDTC were also synthesized by the same enzymatic methods for comparison on different TAC contents. The structures of monomer and copolymers were characterized by (1)H-NMR, (13)C-NMR and FTIR. All the amphiphilic block copolymers could self-assemble to form nano-sized micelles in aqueous solution. Transmission electron microscopy (TEM) observation showed that the micelles dispersed in spherical shape with nano-size before and after MTX loading. (1)H-NMR and FTIR results confirmed the successful formation of multiple hydrogen-bonding interactions between exposed thymine groups of hydrophobic PTAC segments and 2,6-diaminopyridine (DAP) groups of MTX molecules, which resulting in the higher drug loading capacity and the pH-sensitive drug release behavior. MTT assays also indicated lower toxicity of copolymer but higher potent cytotoxic activity of MTX-loaded copolymer against HeLa cells.
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, China.
authors.forename: Dong-Bing
authors.initials: DB
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, China.
authors.forename: You-Mei
authors.initials: YM
authors.lastname: Li
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, China.
authors.forename: Yin-Jia
authors.initials: YJ
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, China.
authors.forename: Xiu-Peng
authors.initials: XP
authors.lastname: Chang
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, China. Electronic address: hefeng@whu.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: He
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, China.
authors.forename: Ren-Xi
authors.initials: RX
authors.lastname: Zhuo
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage*; D011108:Polymers / Q000737:chemistry*; D013941:Thymine / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D011108:Polymers; D013941:Thymine; D008727:Methotrexate
keywords: High loading capacity; Micelle; Multiple hydrogen-bonding interactions; Polycarbonates