Synthesis of Amphiphilic Alternating Polyesters with Oligo(ethylene glycol) Side Chains and Potential Use for Sustained Release Drug Delivery

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• 作者：Wei Wang ; Jianxun Ding ; Chunsheng Xiao ; Zhaohui Tang ; Di Li ; Jie Chen ; Xiuli Zhuang ; Xuesi Chen
• 刊名：Biomacromolecules
• 出版年：2011
• 出版时间：July 11, 2011
• 年：2011
• 卷：12
• 期：7
• 页码：2466-2474
• 全文大小：1143K
• 年卷期：v.12,no.7(July 11, 2011)
• ISSN：1526-4602

文摘

Novel amphiphilic alternating polyesters, poly((N-phthaloyl-l-glutamic anhydride)-co-(2-(2-(2-methoxyethoxy)ethoxy)methyl)oxirane) (P(PGA-co-ME₂MO)), were synthesized by alternating copolymerization of PGA and ME₂MO. The structures of the synthesized polyesters were characterized by ¹H NMR, ¹³C NMR, FT-IR, and GPC analyses. Because of the presence of oligo(ethylene glycol) (OEG) side chains, the polyesters could self-assemble into thermosensitive micelles. Dynamic light scattering (DLS) showed that these micelles underwent thermoinduced size decrease without intermicellar aggregation. In vitro methyl thiazolyl tetrazolium (MTT) assay demonstrated that the polyesters were biocompatible to Henrietta Lacks (HeLa) cells, rendering their potential for drug delivery applications. Two hydrophobic drugs, rifampin and doxorubicin (DOX), were loaded into the polyester micelles and observed to be released in a zero-order sustained manner. The sustained release could be accelerated in lower pH or in the presence of proteinase K, due to the degradation of the polyester under these conditions. Remarkably, in vitro cell experiments showed that the polyester micelles accomplished fast release of DOX inside cells and higher anticancer efficacy as compared with the free DOX. With enhanced stability during circulation condition and accelerated drug release at the target sites (e.g., low pH or enzyme presence), these novel polyesters with amphiphilic structures are promising to be used in sustained release drug delivery systems.