叶酸修饰pH敏感聚酰胺-胺多柔比星复合物的合成及表征

Synthesis and Characterization of FA Modified pH-sensitive PAMAM Doxorubicin Conjugates

目的:合成及表征叶酸(FA)修饰的pH敏感聚酰胺-胺(PAMAM)多柔比星(DOX)复合物。方法:FA、聚乙二醇(PEG)及DOX通过酰胺、酯的肼解反应连接到PAMAM的外周。采用薄层色谱(TLC)、红外光谱(IR)、氢核磁共振(1H-NMR)表征合成产物,考察复合物的载药量、粒径、Zeta电位、形态以及DOX的体外释放行为。结果:合成的复合物连接了8个FA及10个DOX分子,TLC、IR、1H-NMR均证实了复合物为目标化合物。复合物粒径为(75.2±0.25)nm,Zeta电位为(7.04±0.11)mV,呈类球形。48h内复合物中DOX在pH4.5、5.5、7.4的释放介质中累积释放百分率分别为40%、29%、13%。结论:成功合成了FA修饰的pH敏感复合物,该复合物体外释放呈现pH依赖性。

OBJECTIVE： To synthesize and characterize folic acid （FA） modified pH-sensitive PAMAM doxorubicin conjugates. METHODS： FA, PEG and DOX were connected to PAMAM by amidation and hydrazinolysis reaction of ester. The polymer was characterized by TLC, IR and 1H-NMR, respectively. Drug-loading amount, particle size, Zeta potential, shape and morphology of conjugates were investigated, and the dissolution behavior of DOX in vitro was also investigated. RESULTS： 8 FA and 10 DOX were bonded on the periphery of PAMAM-DOX. The structure of conjugates was firmed as the target conjugates by TLC, IR and 1H-NMR successfully. The particle size and Zeta potential for conjugates were （75.2±0.25） nm and （7.04±0.11） mV, respectively. The morphology of the conjugates was regularly spherical shape. 40% of DOX of conjugates was released at pH 4.5, 29% of DOX was released at pH 5.5 and 13% of DOX was released at pH 7.4 during 48 h. CONCLUSIONS： FA-modified pH-sensitive conjugates are successfully synthesized, which release in pH dependent manner in vitro.