肿瘤靶向喜树碱高分子复合物的合成

Synthesis of tumor targeting camptothecin-polymer compound

目的为了提高喜树碱的水溶性和肿瘤靶向性,合成肿瘤靶向的聚乙二醇修饰喜树碱复合物。方法将喜树碱20-羟基与丁二酸酐反应,引入酯键和羧基,再将该羧基活化;叶酸的羧基也进行活化;将活化的羧基与带有碱性官能团-氨基的载体进行反应,得到目标产物FA-PEG-CPT、FA-PEG-C60-C2H4-CPT和FA-PEG-C60-C6H12-CPT。分别用IR、1H NMR、差示热分析对目标产物进行表征,用HPLC法测定目标产物中喜树碱的质量分数。结果 FA-PEG-CPT、FA-PEG-C60-C2H4-CPT和FA-PEG-C60-C6H12-CPT复合物中的喜树碱质量分数分别为7.2%、5.6%、6.5%,DSC特征吸热峰分别为58、70、62℃。结论合成了喜树碱的肿瘤靶向高分子复合物,该复合物具有较理想的载药量。

Objective To improve the solubility,stability and tumor targeting of camptothecin(CPT),20-linked camptothecin-polymer compounds have been synthesized.Methods 20(S)-O-succinyl camptothecine was synthesized by esterification with succinic anhydride.The carboxyl groups of 20(S)-O-succinyl camptothecine and folic acid were activated,respectively.The activated carboxyl groups were then reacted with the amine groups of the polymer carrier,generating folic acid grafted camptothecin-polymer compounds:FA-PEG-CPT,FA-PEG-C 60-C 2H 4-CPT and FA-PEG-C 60-C 6H 12-CPT.The chemical structures of the compounds were characterized by IR and 1H NMR.HPLC method was used for the determination of CPT content in the compounds.Results The content of CPT in FA-PEG-CPT,FA-PEG-C 60-C 2H 4-CPT and FA-PEG-C 60-C 6H 12-CPT was 7.2%,5.6%,6.5%.DSC endothermic peaks of the products were at 58,70,62℃,respectively.Conclusion The tumor targeting camptothecin-polymer compounds were synthesized with ideal drug content.