依折麦布固体脂质纳米粒的制备与大鼠体内药动学研究  

Preparation of ezetimibe solid lipid nanoparticles and study of pharmacokinetics in rats

作　　者：邱爱丽 王敏[2] 谢鹏[1] 祁静波 QIU Aili;WANG Min;XIE Peng;QI Jingbo(Department of Pharmacy,Tangshan Union Hospital,Tangshan 063000,China;Tangshan Vocation&Technical College,Tangshan 063000,China)

机构地区：[1]唐山市协和医院药剂科,唐山063000 [2]唐山职业技术学院,唐山063000

出　　处：《西北药学杂志》2021年第4期611-615,共5页Northwest Pharmaceutical Journal

摘　　要：目的制备依折麦布固体脂质纳米粒(EZE-SLNs),在该处方基础上加入D-α-维生素E聚乙二醇1000琥珀酸酯(TPGS),制备基于TPGS表面修饰的EZE-SLNs(TPGS-EZE-SLNs),并考察2种载药固体脂质纳米粒经大鼠灌胃给药后的生物利用度。方法采用乳化超声-低温固化法分别制备EZE-SLNs和TPGS-EZE-SLNs,通过激光粒度仪分别测定EZE-SLNs与TPGS-EZE-SLNs的粒径分布、多聚分散系数(PDI)和Zeta电位,在透射电镜下观察2种纳米粒的微观形态;反向透析法评价纳米粒的体外药物释放行为;比较EZE-SLNs和TPGS-EZE-SLNs经大鼠灌胃给药后的体内药动学特征。结果EZE-SLNs和TPGS-EZE-SLNs的粒径分布分别为(89.3±6.7)、(92.4±9.1)nm,PDI分别为(0.204±0.009)、(0.199±0.012),Zeta电位分别为(-36.9±1.6)、(-39.7±1.1)mV,在透射电镜下可观察到EZE-SLNs和TPGS-EZE-SLNs均呈球形分布,大小均匀;体外药物释放显示出2种固体脂质纳米粒均提高了药物释放度;大鼠经灌胃给药后体内药动学结果显示,EZE-SLNs和TPGS-EZE-SLNs均能缩短药物的达峰时间(t max),提高药物的达峰质量浓度(C max)和药时曲线下面积(AUC 0~∞),但TPGS-EZE-SLNs提高更为显著。结论制备的TPGS-EZE-SLNs能够提高药物在大鼠体内的吸收速率,显著增加药物的生物利用度。Objective To prepare ezetimibe solid lipid nanoparticles(EZE-SLNs)and D-α-vitamin E polyethylene glycol 1000 succinate(TPGS)surface modified ezetimibe solid lipid nanoparticles(TPGS-EZE-SLNs).The bioavailability of EZE-SLNs and TPGS-EZE-SLNs after intragastric administration in rats was investigated.Methods The EZE-SLNs and TPGS-EZE-SLNs were prepared by emulsification ultrasonic-low temperature curing method.The particle size distribution,polydispersity coefficient(PDI)and Zeta of EZE-SLNs and TPGS-EZE-SLNs were measured by laser particle size analyzer.The microscopic morphology of the 2 nanoparticles was observed under transmission electron microscope.The in vitro drug release behavior of the EZE-SLNs and TPGS-EZE-SLNs was evaluated by reverse dialysis method.The bioavailability of the 2 drug-loaded solid lipid nanoparticles after intragastric administration in rats was investigated.Results The particle size distributions of EZE-SLNs and TPGS-EZE-SLNs were(89.3±6.7)nm and(92.4±9.1)nm,PDI was(0.204±0.009)and(0.199±0.012),and the Zeta potential was(-36.9±1.6)mV and(-39.7±1.1)mV,respectively.Both EZE-SLNs and TPGS-EZE-SLNs had a spherical distribution with uniform particle size under the transmission electron microscope.The in vitro drug release showed that both EZE-SLNs and TPGS-EZE-SLNs improved the degree of drug release.The in vivo pharmacokinetic results showed that both EZE-SLNs and TPGS-EZE-SLNs could shorten the peak time(t max),and increase the peak concentration(C max)and the time curve Area(AUC 0-∞),but the improvement of TPGS-EZE-SLNs was more significant.Conclusion The TPGS-EZE-SLNs prepared can improve the absorption rate of the drug in rats and significantly increase the bioavailability of the drug.

关 键 词：依折麦布 固体脂质纳米粒 D-α-维生素E聚乙二醇1000琥珀酸酯(TPGS)表面修饰 乳化超声-低温固化法 生物利用度 

分 类 号：R94[医药卫生—药剂学]