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目的:制备大蒜素聚氰基丙烯酸正丁酯纳米粒,并考察其体外性质、体内药动学性质和组织分布。方法:采用高效液相色谱法测定纳米粒的包封率和载药量,采用透析袋法测定纳米粒体外释放度。通过透射电镜观察纳米粒的外观和表面形态,激光散射粒度分析仪测定粒径分布。高效液相色谱法测定血浆浓度和组织浓度。结果:纳米粒外观圆整表面光滑,纳米粒的平均粒径为113.4nm,粒度分布范围为11.7~146.8nm,载药量为18.57%,包封率为92.87%。大蒜素纳米粒体外释药可用双相动力学方程拟合,方程为100-Q=0.781 8e-0.323 1t+0.632 2e-0.038 73t。大蒜素注射液和大蒜素聚氰基丙烯酸正丁酯纳米粒静脉给药后,均符合双室模型特征。与注射液组相比,大蒜素聚氰基丙烯酸正丁酯纳米粒在家兔体内的消除半衰期显著延长,t1/2从1.66h延长至5.32h,AUC显著增高,清除率降低,大蒜素聚氰基丙烯酸正丁酯纳米粒较DATS注射液对肝脏靶向性显著提高,肝脏中的相对摄取率re为7.361;肝脏内峰浓度提高到3.38倍;肝脏总靶向效率Te从5.17%提高至40.33%。结论:大蒜素纳米粒制备工艺简单、重现性好,体内具有良好的缓释效果和肝靶向性。
OBJECTIVE: To prepare allicin polybutylcyanoacrylate nanoparticles and study its in vitro properties, in vivo pharmacokinetics and tissue distribution. Methods: The encapsulation efficiency and drug loading of nanoparticles were determined by high performance liquid chromatography (HPLC). The release of nanoparticles in vitro was measured by dialysis bag method. The appearance and surface morphology of the nanoparticles were observed by transmission electron microscopy, and the particle size distribution was measured by laser scattering particle size analyzer. Determination of Plasma Concentration and Tissue Concentration by High Performance Liquid Chromatography. Results: The appearance of the nanoparticles was smooth and round. The average particle size of the nanoparticles was 113.4 nm. The particle size distribution ranged from 11.7 to 146.8 nm. The drug loading was 18.57% and the entrapment efficiency was 92.87%. In vitro release of allicin nanoparticles can be fitted by a two-phase kinetic equation, the equation is 100-Q = 0.781 8e-0.323 1t + 0.632 2e-0.038 73t. Allicin injection and Allicin polybutylcyanoacrylate nanoparticles intravenous administration, are in line with the characteristics of the double chamber model. Compared with the injection group, the elimination half life of allicin polybutylcyanoacrylate nanoparticles in rabbits was significantly prolonged, t1 / 2 extended from 1.66h to 5.32h, AUC was significantly increased, the clearance rate decreased, allicin N-Butyl cyanoacrylate nanoparticles significantly increased liver targeting compared with DATS injection, the relative rectal uptake rate in liver was 7.361; the peak internal liver concentration was increased to 3.38 times; the total liver targeting efficiency Te was increased from 5.17% to 40.33%. Conclusion: Allicin nanoparticles preparation process is simple, reproducible, with good sustained release and liver targeting in vivo.