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目的制备羧基化三维有序大孔炭载体,提高水难溶性药物羟基喜树碱的溶出度。方法采用硬模板法制备三维有序大孔炭载体,以扫描电子显微镜(scanning electron microscopy,SEM)进行表征。采用表面氧化法进行羧基化修饰,对修饰前后的载体进行IR表征及Zeta电位测定。采用溶剂挥发法载药,测定载药量并对载药体系的水分散性进行考察。以DSC考察药物于载体中的存在状态,对原料药及羧基化修饰前后的载药体系的药物溶出度进行测定。结果制得的三维有序大孔炭载体孔道呈互相连通的三维结构,外孔孔径为500nm,内孔孔径为200nm。羧基化修饰后载体的Zeta电位显著降至-16mV,IR谱图中可见明显的羧基吸收峰。羟基喜树碱的载药量质量分数约为24%,羧基化修饰的载药体系水分散性显著提高,DSC显示其中所载药物的结晶峰明显减弱。原料药1h累计释放度仅为24.7%,羧基化修饰的载药体系药物累计释放度升至83.6%。结论制备的羧基化三维有序大孔炭载体可利用其独特的结构特征及改善的水分散性显著提高羟基喜树碱的溶出度。
Objective To prepare carboxylated three-dimensional ordered macroporous carbon support and improve the dissolution of hydroxycamptothecin, a water-insoluble drug. Methods Three-dimensional ordered macroporous carbon supports were prepared by hard template method and characterized by scanning electron microscopy (SEM). Carboxylation modification was carried out by the surface oxidation method, IR characterization and Zeta potential measurement were performed on the carriers before and after modification. The method of solvent evaporation was used to determine the drug loading and the water dispersibility of the drug loading system was investigated. The drug dissolution status of the drug substance and the drug-loading system before and after the carboxylation modification was determined by DSC with the presence of the drug in the carrier. Results The pores of the three-dimensional ordered macroporous carbon support were interconnected with three-dimensional structure. The outer pore diameter was 500 nm and the inner pore diameter was 200 nm. Zeta potential of the carboxylated modified carrier significantly decreased to -16mV, visible carboxyl absorption peak in the IR spectrum. The mass fraction of hydroxycamptothecin was about 24%, and the water dispersibility of carboxylated modified drug-loaded system was significantly increased. DSC showed that the crystal peak of the drug contained therein was obviously weakened. The cumulative release of APIs was only 24.7% at 1h, and the cumulative release of the drug-modified drug-loaded system increased to 83.6%. Conclusion The prepared carboxylated three-dimensional ordered macroporous carbon support can significantly improve the dissolution rate of hydroxycamptothecin with its unique structural characteristics and improved water dispersibility.