文献：Pharmacokinetics of a ternary conjugate based pH-responsive 10-HCPT prodrug nano-micelle delivery system

文献链接：https://www.sciencedirect.com/science/article/pii/S1818087617302477

作者：Yang Liu , Juan Li , Zhi Li , Xing Tang, Zhenzhong Zhang

相关产品：MeO-PEG2000-COOH

原文摘要：A pH-responsive conjugate based

10-hydroxycamptothecin-thiosemicarbazide-polyethene glycol 2000 (10-HCPT-hydro-PEG) nano-micelles were prepared in our previous study. In the present study, ultra-performance liquid chromatography (UPLC-MS) method is developed to investigate its pharmacokinetics and biodistribution in tumor bearing mice. The results demonstrated that the conjugate circulated for a much longer time in the blood circulation system than commercial 10-HCPT injection, and bioavailability was significantly improved compared with 10-HCPT. In vivo biodistribution study showed that the conjugate could enhance the targeting and residence time in tumor site.

MeO-PEG2000-COOH 是一种 PEG 衍生物。它由甲氧基聚乙二醇（MeO-PEG）和羧基（COOH）组成。聚乙二醇链段赋予了该产品良好的水溶性和生物相容性。甲氧基的存在使其在反应中有特定的活性位点。而羧基则为其带来了化学反应活性，可以与多种官能团发生反应。

MeO-PEG2000-COOH 可用于药物的修饰，提高药物的水溶性、稳定性和生物利用度，延长药物在体内的循环时间。基于其优势制备了一种基于ph响应性共轭物的10-HCPT-氢peg纳米胶束。

图：10-HCPT氢PEG示意图

研究用MeO-PEG2000-COOH与10-羟基喜树碱（HCPT）合成了一种水溶性的10-HCPT-氢-peg前药，其Treatment 作用机制是基于靶向核酶拓扑异构酶I（TopoI），通过稳定一个可裂解的复合物来抑制DNAs期复制和RNA转录实现抗Cancer活性，MeO-PEG2000-COOH使10-HCPT的溶解度增加。该连接子包含一个pH敏感的联氨键，它在tumor细胞的酸性环境中断裂并释放药物。该共轭物具有两亲性，可在水中自组装成纳米胶束。

图：ph响应性聚合药物偶联物的示意图。

结论：与10-HCPT注射相比，MeO-PEG2000-COOH参与制备的10-HCPT-氢peg纳米胶束偶联物在体内循环系统中循环时间要长得多，与10-HCPT相比，生物利用度提高。体内生物分布研究表明，该偶联物可以提高tumor部位的靶向性和停留时间。