9-硝基喜树碱脂质体的制备及大鼠肺部给药药动学

Preparation of 9-Nitrocamptothecin liposome and its pharmacokinetic after pulmonary delivery to rats

目的制备9-硝基喜树碱(9-NC)脂质体,研究其经大鼠肺部给药后的体内药动学行为。方法以薄膜分散-超声法制备9-NC脂质体,用粒度测定仪测定粒径,采用离心法分离脂质体和未包封药物并用HPLC法测定包封率,通过肺部滴注给药考察脂质体在大鼠体内的药动学行为,用液液萃取法处理血浆样品,反相HPLC法测定不同时间点大鼠血浆中的药物浓度。结果9-NC脂质体平均粒径为167.6nm,包封率为(91.51±2.63)%(n=3)。9-NC脂质体和溶液剂经肺部给药后,体内药物动力学参数分别为t1/2(3.88±0.90)h和(0.72±0.07)h,AUC0→t(215.88±16.47)μg·h·L-1和(95.29±6.04)μg·h·L-1,MRT(3.72±1.65)h和(1.10±0.08)h。结论与溶液剂相比,9-NC脂质体肺部给药后具有一定的缓释作用。

Purpose To prepare 9-nitrocamptothecin liposomes and study the pharmacokinetic characteristics in rats after pulmonary delivery. Methods 9-nitrocamptothecin liposomes were prepared by thin film dispersion-sonication method and the particle size was determined by particle sizing system. The liposomes and the unloaded drug were separated by centrifugation and the entrapment efficiency of the liposomes was studied by HPLC. The pharmacokinetic characteristics were studied via intratracheal instillation administration to rats. The plasma samples were prepared with liquid-liquid extraction and the drug plasma concentrations were analyzed by RP-HPLC method. Results The mean particle size of the liposomes was 167.6nm and the entrapment efficiency was （91.51 ± 2.63）% （n = 3）. After pulmonary administration to rats, the pharmacokinetic parameters of 9-NC liposome and solution are as follows; t1/2 （3.88 ± 0.90） h and （0.72 ± 0.07） h, AUC0→t （215.88 ± 16.47） μg · h · L^-1 and （95.29±6.04） μg · h · L^-1,MRT （3.72± 1.65） h and （1.10±0.08） h. Conclusions Compared with 9-NC solution, the liposomes show sustained-release characteristics.