马钱子碱免疫纳米微粒的研制及药代动力学特点

背景：由于马钱子碱具有剧毒、难溶于水、静脉应用治疗窗窄、中毒量与治疗量接近等缺点,限制了其临床应用于肝癌等恶性肿瘤的治疗.目的：研制马钱子碱免疫纳米微粒,观察马钱子碱免疫纳米微粒体内药物代谢特点.方法：利用阴离子聚合和化学改性技术制备羧基化聚乙二醇-聚乳酸嵌段共聚物,采用超声乳化技术制备羧基化聚乙二醇-聚乳酸嵌段共聚物马钱子碱纳米微粒,化学偶联技术将马钱子碱纳米微粒与抗人甲胎蛋白单克隆抗体结合,研制具有免疫靶向特点的药物制剂马钱子碱免疫纳米微粒.结果与结论：马钱子碱免疫纳米微粒外观圆整,大小较均一,平均粒径（249±77） nm,Zeta 电位（-18.7±4.19） mV.马钱子碱包封率（76.0±2.3）%,载药量（5.6±0.2）%.马钱子碱免疫纳米微粒在释放介质中24 h 累积释放80%以上,48 h 释放完全.马钱子碱免疫纳米微粒在体内代谢过程属于非房室模型,半衰期为（15.69±3.77） h,显著长于马钱子碱半衰期（P 〈 0.01）.提示实验成功研制了免疫靶向药物马钱子碱免疫纳米微粒,马钱子碱免疫纳米微粒在体内代谢过程属于非房室模型,表现出明显的缓释性.

Preparation and pharmacokinetics of brucine immuno-nanoparticles

BACKGROUND： Brucine is highly toxic and insoluble in water, as well as has narrow intravenous therapeutic window. The amount of poisoning and treatment is close. Therefore, brucine is limited in clinical treatment of liver cancer and other malignant tumors. OBJECTIVE： To prepare the brucine immuno-nanoparticles and to observe the characteristics of the drug metabolism in vivo. METHODS： Anionic polymerization and chemical modification technology were used to prepare carboxylated polyethylene glycol-poly lactic acid copolymer. Phacoemulsification technology was employed to prepare carboxylated polyethylene glycol-polylactic acid copolymer brucine nanoparticles. Then, chemical coupling technology was utilized to combine the anti-human alpha-fetoprotein monoclonal antibody with the polyethylene glycol-poly lactic acid copolymer brucine nanoparticles to prepare the brucine immuno-nanoparticles with immune targeting. RESULTS AND CONCLUSION： Brucine immuno-nanoparticles showed uniform size with an average particle size of （249±77） nm and Zeta potential of （18.7±4.19） mV. The encapsulation efficiency was （76.0±2.3）% and the drug load was （5.6±0.2）%. Brucine immuno-nanoparticles were very stable in the medium with an accumulative release rate of over 80% in 24 hours and 100% in 4B hours. Brucine immuno-nanoparticles belonged to non-compartment model during in vivo metabolic process. The half life period of brucine immuno-nanoparticles was （15.69_＋3.77） hours, which was longer than that of the brucine （P 〈 0.01 ）. The brucine immuno-nanoparticles with immune targeting are successfully prepared that belong to non-compartment model during in vivo metabolic process, and show sustained-release properties.