共价负载阿霉素栓塞微球的制备及缓释性能研究

Studies on the preparation and covalent-loading and release properties of embolic microspheres for doxorubicin

通过反相悬浮方法制备了直径在300～ 500 μm的交联聚乙烯醇微球,以二甲基氨基吡啶为催化剂,使聚乙烯醇微球表面的羟基与丁二酸酐反应生成聚乙烯醇丁二酸酯,再经酯化和酰肼化后得到表面功能化的聚乙烯醇微球.阿霉素通过与微球表面基团形成腙键而负载在微球上,利用腙键的酸敏感性,药物可以在pH控制下释放.结果表明,功能化后的微球可以快速共价负载阿霉素;且随着PBS缓冲液pH值的降低,载药微球对阿霉素的释放速度越快、累计释放量增大.预期将该产物作为血管栓塞剂用于肿瘤治疗,可提高栓塞治疗效果.

Crosslinked polyvinyl alcohol （CPVA） microspheres （300 ～ 500 μm in diameter） were prepared through a direct crosslinking reaction in the suspension polymerization system.The surface of the CPVA was functionalized through the reactions with succinic anhydride,ethanol and hydrazide sequentially.Doxorubicin was covalently loaded on the functionalized CPVA by a formation of hydrazone bond.The drug could be released by pH control.The results showed that the release speed accelerated and cumulative release was increased as the pH was reduced.The product could be used as a vascular embolic agent,and would demonstrate enhanced embolization effect.