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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。结论 硬脂酸纳米粒可能成为一种新型的药物载体
OBJECTIVE To prepare paclitaxel long circulating lipid nanoparticles with stearic acid as carrier material and investigate its in vitro and in vivo properties. Methods Brij78 solid-state lipid nanoparticles (Brij78 SLN) and Poluromic F6 8 solid-state lipid nanoparticles (F6 8 SLN) were prepared by emulsion-solidification at low temperature. The morphology of paclitaxel nanoparticles was investigated by transmission electron microscopy. HPLC method for the determination of paclitaxel in serum, granule and serum. The in vitro drug release of the nanoparticles in 30% ethanol solution was investigated. The pharmacokinetic parameters of the two nanoparticles in mice were determined by the commercial paclitaxel injection. Results The lipid nanoparticles were basically spherical or oval spherical, the size is relatively uniform. The particle size of Brij78 SLN measured by laser light scattering method was (104 ± 2 9) nm. F6 8 SLN particle size (2 2 0 ± 98) nm. The encapsulation efficiencies of Brij78 SLN and F6 8 SLN were 47% and 75%, respectively. Both nanoparticles released the drug slowly, releasing 8% and 20% of the total drug dose after 24 hours, respectively. Both nanoparticles prolonged the in vivo retention time of paclitaxel. The elimination half-lives of Brij78 SLN, F6 8 SLN and paclitaxel injection were 488, 106 and 136 h, respectively. Conclusion Stearic acid nanoparticles may become a new type of drug carrier