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选用氢化大豆磷脂(HSPC)、胆固醇、二硬脂酰磷脂酰甘油(DSPG)为辅料,采用薄膜分散-高压均质法制备卡巴他赛脂质体。以透射电镜观察其形态、动态光散射法测定粒径分布及ζ电位、葡聚糖凝胶柱色谱法测定包封率;采用透析法测定脂质体在体外的释放行为、并测定脂质体在大鼠体内的药动学行为。结果显示,所制得的样品外观和形态较佳、平均粒径为(68.04±1.73)nm、多分散系数为0.213±0.015、ζ电位为(-57.7±1.2)mV、包封率为(86.7±1.5)%。卡巴他赛脂质体在0.05%Tween-80水溶液中的48 h累积释放率为74%,释放速率比注射液(20 h累积释放率为80%)缓慢。卡巴他赛注射液及其脂质体在大鼠体内的AUC_0→∞为(696.89±0.16)和(4 210.07±0.19)ng·ml~(-1)·h,t_(1/2)为(5.85±0.32)和(7.28±0.40)h,提示脂质体有延缓药物释放的作用。
Liposomal cabazitaxel was prepared by membrane dispersion-high pressure homogenization using hydrogenated soybean phospholipid (HSPC), cholesterol and DSPG as excipients. The morphology was observed by transmission electron microscopy, the particle size distribution and zeta potential were determined by dynamic light scattering, and the entrapment efficiency was determined by dextran gel column chromatography. The release behavior of liposomes in vitro was determined by dialysis method. Pharmacokinetic behavior in rats. The results showed that the obtained sample had good appearance and morphology with an average particle size of (68.04 ± 1.73) nm, a polydispersity of 0.213 ± 0.015 and a zeta potential of (-57.7 ± 1.2) mV with an encapsulation efficiency of (86.7 ± 1.5)%. The cumulative release rate of cabazitaxel liposomes in the 0.05% Tween-80 aqueous solution at 48 h was 74%, and the release rate was slower than that of the injection solution (20 h cumulative release rate was 80%). The AUC 0 → ∞ of captopril injection and its liposome in rats were (696.89 ± 0.16) and (4 210.07 ± 0.19) ng · ml -1 · h, respectively, t 1/2 was 5.85 ± 0.32) and (7.28 ± 0.40) h, suggesting that the liposomes can delay the release of drugs.