喜树碱-聚乙二醇前药的合成及体内外释药特性

为提高喜树碱（CPT）在体内的代谢稳定性，合成喜树碱-聚乙二醇前药。以聚乙二醇为原料,经过端基活化，与喜树碱20-位羟基反应得到目标化合物（6a-6e），分别用IR、¹H NMR对化合物6a-6e进行了结构表征。用HPLC法测定化合物6a-6e在磷酸缓冲液（pH 7.4）中释放的喜树碱浓度，以及大鼠血浆中释放的喜树碱浓度。结果表明化合物6a-6e在磷酸缓冲液中24 h的药物释放速率在11%~52%之间；大鼠尾静脉给药，表明化合物6a-6e的AUC为CPT溶液剂的4.38倍至6.67倍。化合物6a-6e具有比CPT更好的体内稳定性，有望延长药物体内半衰期及提高生物利用度。

Synthesis and characterization of camptothecin-polyethylene glycol ester prodrugs

To improve the metabolic stability of camptothecin (CPT) in vivo,a series of 20-PEG-linked camptothecin prodrugs were synthesized.After activation of hydroxy groups at the two ends of polyethylene glycol (PEG),CPT was coupled to the activated PEG to give the targeted products 6a-6e.The chemical structures of 6a-6e were characterized by IR and ¹H NMR.HPLC method was used for the determination of CPT concentration in PBS buffer (pH 7.4) and in plasma of rats.Drug releasing rates from 6a-6e in PBS buffer (pH 7.4) were 11%-52% within 24 h.When given to rats intravenously,AUC of compounds 6a-6e were 4.38 to 6.67 fold higher than that of CPT solution.Compunds 6a-6e have longer circulation effects,substantially greater than CPT.They can prolong biological half-life and improve the bioavailability of camptothecin.