Synthesis of an amphiphilic graft copolymer bearing a hydrophilic poly(acrylate acid) backbone for drug delivery of methotrexate. Issue 86 (28th November 2017)

• Record Type: Journal Article
• Authors: Wang, Wei; Zhou, Xin; Wei, Min; Liu, Zude; Lu, Guolin; Huang, Xiaoyu
• Is Part Of: RSC advances. Volume 7:Issue 86(2017)
• Page Start: 54562
• Page End: 54569
• Publication Date: 2017-11-28
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c7ra11975e
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : This article reports the synthesis of a PAA- g -PLA amphiphilic graft polymer, which could self-assemble into large compound micelles in aqueous media for sustained release of MTX. Abstract : A well-defined amphiphilic graft copolymer consisting of a hydrophilic poly(acrylic acid) (PAA) backbone and hydrophobic poly(lactic acid) side chains was synthesized by the combination of reversible addition–fragmentation chain transfer (RAFT) polymerization, ring open polymerization (ROP), and the grafting-from strategy. RAFT homopolymerization of an OH-containing tert -butyl 2-((4-hydroxy-butanoyloxy)methyl)acrylate ( t BHBMA) monomer was first conducted to give a well-defined P t BHBMA homopolymer bearing pendant hydroxyls in every repeat unit. The pendant hydroxyls of P t BHBMA directly initiated the ROP of lactide without post-polymerization functionality transformation so as to provide a well-defined poly( tert -butyl acrylate)- g -poly(lactic acid) (P t BA- g -PLA) graft copolymer via the grafting-from strategy. The hydrophobic P t BA backbone was transformed into a hydrophilic PAA backbone to afford the target well-defined PAA- g -PLA amphiphilic graft copolymer ( M w / M n = 1.17) containing equally-distributed carboxyls along the backbone. The PAA- g -PLA amphiphilic graft copolymer shows pH-responsive micellization behavior and it can self-assemble into non-toxic large compound micelles under certain conditions for loading methotrexate (MTX). The in vitro accumulative release characteristics of MTX-loaded micelles were investigated by UV/vis spectroscopy. In comparison with free MTX, the MTX-loaded nanoparticles display higher cytotoxicity against MG-63 in 24, 48 and 72 h.