离子载体A23187介导pH梯度法制备重酒石酸长春瑞滨长循环脂质体  

Preparation of vinorelbine bitartrate long-circulating liposomes by ionophore A23187-mediated pH gradient method

作　　者：杨光丽 张冰 赵利刚 张勇 王栋海 尹青 杨清敏 

机构地区：[1]山东省注射用微粒给药新技术重点实验室,济南250100 [2]齐鲁制药有限公司药物研究院,济南250100

出　　处：《中国新药杂志》2012年第3期251-256,共6页Chinese Journal of New Drugs

基　　金：国家"重大新药创制"科技重大专项(2010ZX09401-302-4-2);"泰山学者"建设工程专项资助(2009年)

摘　　要：目的:采用A23187制备重酒石酸长春瑞滨长循环脂质体,优化了处方工艺,并考察了含量、包封率、药脂比和体外释放等检测指标。方法:采用A23187介导的pH梯度法制备了重酒石酸长春瑞滨脂质体;用HPLC法检测了脂质体中重酒石酸长春瑞滨的含量和脂质(HSPC)的含量,考察了药脂比;采用阳离子交换树脂分离脂质体和游离药物,HPLC法检测包封率;以4 mmol.L-1NH4Cl-PBS(pH 7.4)为体外释放介质考察了脂质体的体外释放行为。结果:重酒石酸长春瑞滨脂质体包封率为96.1%,药脂比为1∶5(w/w);高药脂比有利于延长药物体外释放的时间。结论:采用A23187介导的pH梯度法制备重酒石酸长春瑞滨脂质体工艺可行、载药量大、包封率高;所建立体外释放的检测方法快速、准确。Objective： To prepare vinorelbine bitartrate long-circulating liposomes and optimize the formulation and process parameters, and to investigate vinorelbine contents, entrapment efficiency, drug-to-lipid ratio, in vitro release rate of the liposomal vinorelbine. Methods： Vinorelbine bitartrate liposomes were prepared in response to a transmembrane pH gradient that was generated by the use of ionophore A23187. Drug-to-lipid ratio was calculated by vinorelbine bitartrate content and HSPC content that were determined by HPLC. Free vinorelbine and lipo- somal vinorelbine were separated by cation exchange resin ultraviolet, and the encapsulation efficiency was determined by HPLC. The in vitro release behavior was investigated in 4 mmol· L^-1 NH4Cl-PBS （pH 7.4）. Results： The encapsulation efficiency and drug-to-lipid ratio of the vinorelbine liposomes were 96.1% and 1：5 （mass ratio） , respectively. The higher drug-to-lipid ratio reduced the in vitro release rate of vinorelbine from liposomes. Conclusion： The ionophore A23187-1oading technique is feasible for preparing vinorelbine bitartrate long-circulating liposomes. The drug loading and encapsulation efficiency are desirable. The determination method of in vitro release was simple, rapid and accurate.

关 键 词：重酒石酸长春瑞滨 脂质体 离子载体 A23187 体外释放 

分 类 号：R943.4[医药卫生—药剂学] R979.1[医药卫生—药学]