TPGS修饰的盐酸吉西他滨脂质体的研制  

Preparation of Gemcitabine Hydrochloride Liposomes Modifi ed by TPGS

作　　者：冯悦[1] 钟萌[2] 陈跃[1] 

机构地区：[1]泸州医学院附属医院核医学科,四川泸州646000 [2]泸州医学院附属医院药剂科,四川泸州646000

出　　处：《中国医药工业杂志》2016年第1期39-43,共5页Chinese Journal of Pharmaceuticals

基　　金：四川省医学重点学科建设项目(2008-17)

摘　　要：为延长盐酸吉西他滨(1)的半衰期、提高生物利用度,采用逆相蒸发法制备聚乙二醇1000维生素E琥珀酸酯(TPGS)修饰的1脂质体(1-LP),并考察其性质和在大鼠体内的药动学行为。结果表明,所得1-LP的粒径为(212.6±7.2)nm、z电位为(-31.1±2.9)m V、包封率为(70.56±1.92)%、载药量为(7.41±0.05)%。绘制了1-LP和1水溶液在p H 7.4磷酸盐缓冲液中的体外释药曲线,并用几种常用模型拟合试验数据。结果二者的释药数据均用双指数模型拟合效果较好(R^2为0.996和0.947)。对比研究了SD大鼠尾静脉注射给予1-LP或市售1注射液后的药动学行为。血浆中的药物浓度采用HPLC法测定。所得主要药动学参数为:t_(1/2)(4.12±0.73)和(1.32±0.10)h,AUC_(0→∞)(37.57±1.09)和(9.64±0.20)mg·L·h^(-1),MRT_(0→∞)(6.06±0.28)和(1.67±0.04)h。To improve the half time and bioavailability of gemcitabine hydrochloride （1）, the 1 liposomes （1-LP） modified by D-α-tocopheryl polyethylene glycol 1000 succinate （TPGS） were prepared by reverse evaporation method. The properties and pharmacokinetics of the product in rats were investigated. The results showed that the average particle size, ζ potential, entrapment efficiency and drug loading were （212.6±7.2）nm, （-31.1±2.9） mV, （70.56±1.92） % and （7.41±0.05） %, respectively. The in vitro release curves of 1-LP and 1 solution in pH 7.4 phosphate buffer were drawn and the experimental data were fitted by serval commonly used models. The results showed that a biexponential model fitted the data well according to the correlation coefficient （R2） values, which were 0.996 and 0.947. After vein injection of 1-LP or commercially available injection of 1, the pharmacokinetics of both preparations in SD rats were investigated and compared. The drug concentration in plasma was determined by HPLC. The main pharmacokinetic parameters of 1-LP and 1 injection were as follows： t1/2（4.12±0.73） and （1.32±0.10）h, AUC0-∞ （37.57±1.09） and （9.64±0.20）mg.L.h ^-1, MRT0→∞ （6.06±0.28） and （1.67±0.04）h.

关 键 词：盐酸吉西他滨 聚乙二醇1000维生素E琥珀酸酯(TPGS) 脂质体 体外释放 药动学 

分 类 号：R944.9[医药卫生—药剂学]