| 张 雨,乔友备,周 青,余 喆,吴 红.聚苹果酸合成新方法及其聚苹果酸苄基酯用作药物载体的研究[J].现代生物医学进展英文版,2018,(10):1849-1853. |
| 聚苹果酸合成新方法及其聚苹果酸苄基酯用作药物载体的研究 |
| Synthesis of Poly (β-malic acid) and Study on Poly (β-malic Acid benzyl ester) as Drug Carrier |
| Received:December 25, 2017 Revised:January 18, 2018 |
| DOI：10.13241/j.cnki.pmb.2018.10.009 |
| 中文关键词: 聚苹果酸苄基酯 阴离子开环聚合 聚苹果酸 纳米胶束 |
| 英文关键词: Poly (β-malic acid benzyl ester) Ring-opening polymerization Poly (β-malic acid) Nanomicelle |
| 基金项目:国家自然科学基金项目（81571786; 31771087）；陕西省科技统筹创新工程项目（2015KTCL03-12） |
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| 中文摘要: |
| 摘要 目的：优化β-聚苹果酸（PMLA）的合成路线，制备部分氢化的聚苹果酸苄基酯（PMLABz），为构建载药纳米胶束提供两亲性聚合物载体。方法：分别以L-天冬氨酸和L-苹果酸为原料，合成单体β-苄氧羰基-β-丙内酯，再通过阴离子开环聚合制备PMLABz，最终氢化制备PMLA。X射线衍射仪、差示扫描量热仪等对材料的性质进行表征，L929成纤维细胞测定聚合物的细胞毒性，透析法制备部分氢化的聚苹果酸苄基酯空白胶束。结果：通过优化反应条件，以L-苹果酸为原料合成关键中间体β-苄氧羰基-β-丙内酯的终产率为31.5 %，对比文献报道的L-天冬氨酸合成路线，产率提高近7倍。X-RD结果表明以L-苹果酸为原料制备的PMLABz有明显的衍射峰，结晶度高，熔点随之升高，MTT实验证实PMLABz无毒性。部分氢化的PMLABz可在水中自组装成一定粒径的胶束，氢化77 %的PMLABz可得到粒径均匀、形态良好的纳米胶束。结论：分别以L-天冬氨酸和L-苹果酸为原料合成聚苹果酸，优化合成路线，提高终产率，得到了新晶型PMLABz，并通过部分氢化PMLABz制备两亲性聚合物进而得到纳米胶束，为后期纳米释药体系研究提供优良载体。 |
| 英文摘要: |
| ABSTRACT Objective: To optimize the synthesis route of PMLA and prepare the partially hydrogenated poly (β-malic acid benzyl ester) which is to provide the amphiphilic polymer carrier for the drug-loaded nanomicelles. Methods: Benzyl-β-malolactonate (MLABz) was prepared from L-aspartic acid and L-malic acid, respectively. The properties of the polymers were characterized by X-RD and DSC. The cytotoxicity of PMLABz was assessed by using L929 fibroblasts. The partial hydrogenation of PMLABz was prepared by controlling the hydrogenation time to obtain an amphiphilic block copolymer. Results: The yield of MLABz from L-malic acid was 31.5 % nearly seven times as much as the L-aspartic acid by optimizing the reaction conditions. The X-RD patterns revealed that the PM- LABz-2 had obvious diffraction peaks. The melting temperature was increased due to the high crystallinity. MTT test confirmed that the PMLABz was nontoxic. The partial hydrogenation of PMLABz could form the certain size of the nanomicelles by self-assembling in water. It was confirmed that a hydrogenation degree was 77 % of PMLABz which would obtain the well-formed nanomicelles. Conclusion: MLABz was prepared from L-aspartic acid and L-malic acid, respectively. The synthesis routes of PMLA from L-malic acid had the short route and high yield. Meanwhile, a novel crystalline PMLABz that polymerized by MLABz starting from L-malic acid was discovered. An am- phiphilic block polymer was obtained by partial hydrogenolysis of PMLABz which would provide an excellent nanocarrier for drug de- livery system. |
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