K237修饰的紫杉醇热敏脂质体的制备、处方优化和体外释放度研究  

Preparation,prescription optimization and in vitro release of paclitaxel loaded K237 thermosensitve liposome

作　　者：陆媛媛[1,2] 符旭东[2] 邓艾平[1] 刘珏[1] 李凯[1] LV Yuan yuan FU Xu-dong DENG Ai-ping LIU Jue LI Kai(Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical Collegeg, Huzhong University of Science Hubei Wuhan 430014, China Department of Pharmacy,Wuhan General Hospital of Guangzhou Military Area, Hubei Wuhan 430070,China)

机构地区：[1]华中科技大学同济医学院附属武汉中心医院药剂科,湖北武汉430014 [2]广州军区武汉总医院药剂科,湖北武汉430070

出　　处：《中国医院药学杂志》2017年第8期722-726,共5页Chinese Journal of Hospital Pharmacy

基　　金：2011年湖北省科技计划自然科学基金项目(编号:2011CDB019);武汉市卫生局临床医学科研项目(编号:WX11A02)

摘　　要：目的:以紫杉醇(PTX)为模型药物,构建K237修饰的热敏脂质体(K237-PTX-TSL),系统研究K237-PTX-TSL的制备工艺、理化性质,处方优化和体外释放特性。方法:采用NH2末端PEG化技术合成靶向磷脂材料DSPE-PEG-K237,采用薄膜分散法制备K237修饰的紫杉醇热敏脂质体(K237-PTX-TSL),HPLC法测量药物的包封率和载药量;采用马尔文激光粒度仪测定K237-PTX-TSL的粒径及粒径分布和Zeta电位;利用差示扫描量热法(DSC)测量相变温度(Tm);采用透析袋法测量相变温度下的释药规律并拟合释放曲线。结果:优化的处方为:DPPC∶DSPG∶MSPC∶DSPE-PEG-NHS=9∶1∶1∶1,药脂比为1/20,磷脂浓度为5.0%,DSPE-PEG-K237占处方磷脂总量为1%。制备得到的K237-PTX-TSL包封率为(94.23±0.76)%;粒测得K237-PTX-TSL粒径为(88.3±4.7)nm,电荷为-4.5 mv,PDI值为0.13±0.01;K237-PTX-TSL的相变温度为40.805℃,K237-PTX-TSL在42℃时的体外释放最优拟合为一级动力学模型,方程为In(100-Q)=-0.063 8t+4.713 0(r=0.994 4)。42℃时20 min内紫杉醇累计释放度为72.45%,60 min的累计释放度为98.84%。结论:K237修饰的热敏脂质体载药量和包封率较高、粒径较小,热敏释药性质良好,1 h内药物基本释放完全。OBJECTIVE To mainly report studies concerning formulation,preparation technology,physicochemical property and in vitro release characteristics of K237-PTX-TSL.METHODS DSPE-K237-PEG was synthesized by N-terminal PEGylation technique and K235-PTX-TSL was prepared by thin film dispersion method.Entrapment efficiency was determined by minicolumn centrifugation and encapsulation efficiency and drug loading was measured by HPLC method.Laser scattering particle size distribution analyzer was employed to measure particle size,particle size distribution and zeta electric potential.Additionally,differential scanning calorimetry（DSC）was used for phase transition temperature（Tm）measurement.By adopting dialysis bag method,in vitro release behaviors of K235-PTX-TSL were studied at different temperatures.Besides,in vitro release profile at a constant temperature was fitted by different model equations.RESULTS The optimum formulation parameters of K237-PTX-TSL were as follows：DPPC/DSPG/MSPC/DSPE-PEG of 9∶1∶1∶1,paclitaxel/lipid material of 1∶20,lipid material concentration of 5.0% and DSPE-PEG-K237 of 1%.Encapsulation efficiency of K237-PTX-TSL was（94.23±0.76）%.The average size of K237-PTX-TSL was（88.3±4.7）nm,zeta potential was-4.5 mv and PDI was（0.13±0.01）.Phase transition temperature of K237-PTX-TSL was 40.805 ℃.The release of PTX from K237-PTX-TSL was shown to be temperature dependent and in vitro release model was fitting the first order kinetics equation：In（100-Q）=-0.063 8t＋4.713 0（r=0.994 4）.The cumulative release of paclitaxel was 72.45% within20 min at 42 ℃and 98.84% within60 min at 42 ℃.CONCLUSION With small sizes and excellent in vitro drug release characteristics,K237-PTX-TSL shows high drug loading capability and high encapsulation efficiency.

关 键 词：热敏脂质体 紫杉醇 靶向 K237 

分 类 号：R94[医药卫生—药剂学]