万古霉素阳离子脂质体复合纳米羟基磷灰石/壳聚糖/魔芋葡苷聚糖支架的制备与降解及药物的体外释放研究  

Nano-hydroxyapatite/chitosan/konjac glucomannan scaffolds loaded with cationic liposomal vancomycin： preparation, degradation and in vitro release

作　　者：马涛[1] 尚北城[2] 陈庆华[3] 徐帆[2] 周田华[1] 徐永清[1] 

机构地区：[1]昆明,成都军区昆明总医院骨科,650032 [2]昆明,成都军区昆明总医院药剂科,650032 [3]昆明理工大学材料科学与工程学院

出　　处：《中华创伤骨科杂志》2014年第10期891-897,共7页Chinese Journal of Orthopaedic Trauma

基　　金：国家自然科学基金（81171734）;云南省科技厅重点新产品开发项目（2012BC007）;Supported by National Natural Science Foundation of China （81171734） and Development Programs of New Products of Science and Technology Administration of Yunnan Province （2012BC007）

摘　　要：目的 制备万古霉素阳离子脂质体（CLV）复合的纳米羟基磷灰石/壳聚糖/魔芋葡苷聚糖（n-HA/CS/KGM）支架,探讨其在模拟体液中的释放特性, 方法 采用逆向蒸发法制备CLV,将其与n-HA/CS/KGM支架复合,并在扫描电镜下观察复合支架中CLV的形态;采用中国药典推荐的方法Ⅲ溶出装置,研究CLV体外从支架释放的性质和特点,以及6种不同CLV和KGM含量对支架释药行为的影响， 结果 扫描电镜观察显示：CLV复合n-HA/CS/KGM支架完整保存了CLV的结构,首先从支架中释放的主要是CLV而不是游离药物;CLV从支架中释放1h内可以观察到“爆释”现象,整个释放过程可以用基于Frutos等提出的数学模型的改良公式进行良好模拟，无论是KGM还是CLV在支架中的含量对支架的释放行为均有显著影响：当加入CLV的量未达到饱和之前,随着KGM成分的增加或CLV成分的减少,CLV的释放率和释放量都可显著减少,差异有统计学意义（P＜0.05）， 结论 通过调整支架中KGM和（或）CLV成分的含量,可以得到不同释放速率和释放药物比率的复合支架,可满足临床应用的不同需要。Objective To design a novel artificial bone scaffold and investigate its release properties in simulated body fluid.Methods Cationic liposomal vancomycin （CLV） was prepared by a modified reverse phase evaporation method.Porous nano-hydroxyapatite/chitosan/konjac glucomannan （n-HA/CS/KGM） scaffolds were loaded with CLV to form a novel complex drug carrier （LLS）.Scanning electron microscopy was used to determine the microstructures of LLS.A type Ⅲ Chinese Pharmacopoeia dissolution apparatus was used in the drug release studies.The kinetics of CLV release from LLS and the effects of 6 different amounts of konjac glucomannan （KGM） and CLV in LLS were examined in vitro.Results Electron microscopy indicated that the liposomes were well preserved in the scaffolds,and that CLV rather than free vancomycin was released from the scaffolds.An initial burst effect was observed at the first hour.The whole process of CLV release could be well simulated on the basis of a modified Frutos＇ equation.The weight percentage of KGM or CLV greatly influenced the release behavior of the scaffolds.Before saturation of the CLV added,increase of KGM or decease of CLV significantly reduced release of the CLV （P ＜ 0.05）.Conclusion By adjusting the ratio of KGM/CLV,which significantly influenced the release rate of CLV,we successfully prepared customized scaffolds whose different release rates might satisfy diverse therapy requirements.

关 键 词：羟基磷灰石类 壳聚糖 魔芋属 脂质体 万古霉素 

分 类 号：R318.08[医药卫生—生物医学工程]