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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24h累积释放80%以上,48h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。
BACKGROUND: Brucine has the advantages of being highly toxic and insoluble in water, narrow in therapeutic window for intravenous application, and close to the toxic dose and therapeutic amount, which limits the clinical application of brucine in the treatment of malignant tumors such as liver cancer. OBJECTIVE: To develop strychnine-immunized nanoparticles and observe the drug metabolism characteristics of strychnine-immunized nanoparticles in vivo. Methods: The carboxylated polyethylene glycol-polylactic acid block copolymer was prepared by anionic polymerization and chemical modification technology. The strychnine-based nanoparticles of carboxylated polyethylene glycol-polylactide block copolymer were prepared by ultrasonic emulsification. Chemiluminescent coupling of strychnine nanoparticles with anti-human alpha-fetoprotein monoclonal antibody to develop immunostimulatory strychnine immune nanoparticles. RESULTS AND CONCLUSION: The immunogenic nanoparticles of strychnine were round and uniform in size with average particle size (249 ± 77) nm and zeta potential (-18.7 ± 4.19) mV. Strychnine encapsulation efficiency (76.0 ± 2.3)%, drug loading (5.6 ± 0.2)%. Strychnine-immunized nanoparticles in the release medium 24h cumulative release of more than 80%, 48h release completely. The strychnine-immunized nanoparticles were non-compartmentalized in vivo with a half-life of (15.69 ± 3.77) h, which was significantly longer than the half-life of brucine (P <0.01). Prompt experiment successfully developed immunostimulatory strychnine immune nanoparticles, strychnine immune nanoparticles in vivo metabolism of non-compartmental model, showed a significant slow release.