重组人干扰素α-2a聚氰基丙烯酸丁酯肝靶向缓释纳米球冻干剂的研究

Human Recombinant Interferon-α2a Polybutylcyanoacrylate Sustained Release Lyophilized Nanospheres for Liver-Targeting

目的 考察基因重组人干扰素 α- 2 a聚氰基丙烯酸丁酯纳米球冻干制剂 (r IFNα2 a- PBCA- NS)的肝靶向性和缓释性。方法 采用乳化聚合法制备纳米球 ,并制得冻干品 ,用细胞病变抑制法测定制剂及生物样品中r IFNα2 a的含量 ;经小鼠静脉给药后 ,观察其在体内分布和在肝脏中的药代动力学。结果 制得的纳米球平均包封率为 5 6 .2 %± 4 .3% ;r IFNα2 a- PBCA- NS的平均粒径为 (10 8± 37) nm,跨距为 0 .5 5 ;3～ 5℃ ,冻干品留样观察 6个月生物活性指标基本不变。在肝脏中的分布百分率由原药的 13.1%提高到 5 0 .6 % ,在肝脏中的平均滞留时间由原药的 1.4 1h延长到 8.35 h。结论 制备的 r IFNα2 a- PBCA- NS具有明显肝靶向性和缓释特征。

Objective To evaluate the liver-targeted and sustained release characteristics of human recombinant interferan-α2a polybutylcyanoacrylate lyophilized nanospheres (rIFNα2a-PBCA-NS). Methods Emulsification/polymerization method was used to prepare the nanospheres which was lyophilized to obtain rIFNα2a-PBCA-NS, and cell pathological embarrassment (CPE) was used to determine the rIFNα2a concentration in the preparations and biological samples. The in vivo distribution and pharmacokinetics in liver after intravenous injection (i.v.) of rIFNα2a-PBCA-NS and rIFNα2a in mice were evaluated. Results The rate of entrapment of the nanospheres was (56.2±4.3)%; the particle diameter, span of rIFNα2a-PBCA-NS were (108±37) nm and 0.55, respectively, and their biological activity had little change after being stored at 3 5 ℃ for 6 months. The distribution ratio of rIFNα2a after i.v. in mice liver increased from 13.1% (for rIFNα2a) to 50.6% (for rIFNα2a-PBCA-NS), and the mean retain time from 1.41 h (for rIFNα2a) to 8.35 h (for rIFNα2a-PBCA-NS). Of the distribution parameters (t e for rIFNα2a, r e and t e for rIFNα2a-PBCA-NS) in 5 main organs, the largest ones were in liver and both r e and t e for rIFNα2a-PBCA-NS in liver larger than one. Conclusion The rIFNα2a-PBCA-NS showed obviously liver-targeting and sustained release characteristics.