| 乔友备1 张海涛2 李飞1 李伟1 段晓1 成冲1 陶阳春1 吴红1△.聚苹果酸- 羟喜树碱前药的合成和性质初探[J].,2012,12(17):3253-3258 |
| 聚苹果酸- 羟喜树碱前药的合成和性质初探 |
| Prodrug of Poly(β-malic acid)-Hydroxycamptothecin Polymer:Preparation, Characterization and Biological Evaluation |
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| DOI： |
| 中文关键词: 聚合物药物 聚苹果酸 羟喜树碱 药物转运系统 |
| 英文关键词: Polymeric drug Poly(β-malic acid) Hydroxycamptothecin Drug delivery system |
| 基金项目:国家自然科学基金项目（30970788） |
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| 中文摘要: |
| 目的：化学全合成聚苹果酸（poly(β-malic acid), PMLA)，将其作为高分子药物载体，制备聚苹果酸- 羟喜树碱前药(PMLAHCPT）
。研究其体外释药特点和体外细胞毒性。方法：以L- 天冬氨酸为原料，通过化学方法全合成PMLA，通过酰胺键键合羟基喜
树碱(HCPT）。通过红外光谱、核磁共振光谱表征该前药的结构，利用体外动态透析的方法模拟体外释药特点，用高效液相色谱法
测定不同pH 值聚合物药物中前喜树碱的释药特性。采用人卵巢癌HO-8910 细胞系研究该前药的体外毒性。结果：①经核磁共振
表征PMLA-HCPT 前药合成完成。②在pH 5.6、pH 6.8 及pH 7.4 的PBS 缓冲体系16 h 中，羟喜树碱药物累积释放率分别为76.8
%，47.2 %和18.1 %，证实PMLA-HCPT 中羟喜树碱的释放具有pH 依赖性。③细胞实验证实PMLA-HCPT 的细胞毒性和游离的
HCPT 相比没有降低。结论：PMLA 是一种良好的药物载体材料，PMLA-HCPT 有望成为具有pH 敏感性的聚合物前药。 |
| 英文摘要: |
| Objective: Poly (beta-malic acid) (PMLA) was synthesized, and used as polymeric drug carrier. A novel poly(beta-malic
acid)-hydroxycamptothecin conjugate (abbreviated as PMLA-HCPT) for active tumor targeting was set up. Methods: The structure of
this prodrug was confirmed by FT-IR and 1H-NMR. Furthermore, the conjugation efficiency, drug release property of the prodrug was
determined. The cytotoxicity were assessed by using human ovarian cancer HO-8910 cell lines as in vitro cell model. Results: (1) The
conjugates were prepared successfully. (2) In vitro HCPT release from PMLA-HCPT conjugate occurred at a faster rate at acidic pH
compared with neutral pH (7.4). The released free HCPT after 16 h of incubation at pH 5.6, 6.8 and 7.4 was 76.8 %, 47.2 % and 18.1 %,
respectively. (3)The cytotoxicity of PMLA-HCPT conjugates against HO-8910 cells, were not lower than free HCPT. Conclusion: PMLA
is a good drug carrier material. PMLA-HCPT conjugate could be used as a promising hydroxycamptothecin carrier. |
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