紫杉醇长循环固态脂质纳米粒的制备和体内外研究

IN VITRO AND IN VIVO STUDY OF TWO KINDS OF LONG-CIRCULATING SOLID LIPID NANOPARTICLES CONTAINING PACLITAXEL

目的 以硬脂酸为载体材料制备紫杉醇的长循环脂质纳米粒 ,并考察其体内外性质。方法 用“乳化蒸发 低温固化”法制备Brij78固态脂质纳米粒 (Brij78 SLN)和PoluromicF6 8固态脂质纳米粒 (F6 8 SLN) ;用透射电镜考察了紫杉醇纳米粒的形态 ;建立了脂质纳米粒和血清中测定紫杉醇的HPLC方法 ;考察了纳米粒于 3 0 %乙醇溶液中的体外药物释放 ;以市售紫杉醇注射剂对照 ,测定了两种纳米粒于小鼠体内的药物动力学参数。结果 脂质纳米粒基本呈圆球状或椭圆球状 ,大小比较均匀。激光散射法测定Brij78 SLN粒径为 ( 10 4± 2 9)nm。F6 8 SLN粒径为 ( 2 2 0± 98)nm。Brij78 SLN和F6 8 SLN包封率分别为 4 7%和 75 %。两种纳米粒都缓慢地释放药物 ,2 4h后分别释放药物总量的8%和 2 0 %。两种纳米粒都可以延长紫杉醇的体内滞留时间 ,Brij78 SLN ,F6 8 SLN和紫杉醇注射剂的消除半衰期分别为 4 88,10 0 6和 1 3 6h。

AIM To prepare long circulating solid lipid nanoparticles containing paclitaxel with stearic acid, and investigate the in vitro and in vivo characterization of nanoparticles. METHODS The method of “emulsion evaporation solidification at low temperature” was used to prepare the stearic acid solid lipid nanoparticles containing paclitaxel. Its morphology was examined by transmission electron microscope. The HPLC method for determination of paclitaxel in nanoparticles or serum samples was established. The release of paclitaxel in vitro and the pharmacokinetics after iv bolus injection to mice were studied. RESULTS The mean diameter of Brij78 SLN and F 68 SLN is (103 5±29 2) nm and (220±98) nm, respectively. The nanoparticles release paclitaxel slowly and linearly, within 24 h, Brij78 SLN and F 68 SLN release 8% and 20% of total drug, respectively. Long circulation nanoparticles was found to stay in the blood circulation, with T 1/2 β 10 1 h of F 68 SLN, and T 1/2 β 4 88 h of Brij78 SLN more than one commercialized paclitaxel injection, T 1/2 β 1 3 h. CONCLUSION Stearic acid might be a new drug carrier material in the future.