肝靶向阿克拉霉素A固体脂质纳米粒质量考察及体内分布研究

 目的为促进固体脂质纳米粒(SLN)的发展,提高阿克拉霉素A(ACM-A)的疗效,制备具有肝靶向的阿克拉霉素A固体脂质纳米粒(ACM-SLN)冻干针剂,并对其质量和体内组织分布进行研究。方法采用正交设计优化ACM-SLN及其冻干针剂的处方和制备工艺,并研究其形态、粒径及粒径分布、载药量,稳定性和动物体内分布。结果得到的ACM-SLN平均粒径为62 nm,平均载药量为4.41%,平均包封率为88.17%。体内分布研究结果表明,15,30和60 min时ACM-SLN冻干针剂在肝脏中的药物浓度分别为30.379,32.591和30.416 mg·L^-1而对应的ACM-A溶液剂的质量浓度分别为10.795,12.796和10.135 mg·L^-1结论得到的ACM-SLN冻干针剂基本稳定。与ACM-A溶液剂相比,ACM-SLN冻干针剂显著提高了ACM- A在靶器官肝脏中的药物水平。

Study on Quality Control of Liver Targeted Aclacinomycin A Solid Lipid Nanoparticles and Its in vivo Distribution in Mice

OBJECTIVE To investigate the quality control and its tissue distribution of the prepared liver targeted aclacinomycin A solid lipid nanoparticles(ACM-SLN).METHODS The orthogonal design was applied to the optimization of the formula and tech- nology of ACM-SLN.The quality characteristics of its shape,average diameter,particle distribution,drug loading,stability in vitro and tissue distribution in vivo were studied.RESULTS The average diameter of ACM-SLN was 62 nm,drug loading was 4.47% and embedded ratio was 89.32%.The drug concentrations of ACM-SLN in targeted liver in mice were 30.379,32.591 and 30.416 mg·L^-1in 15,30 and 60 min respectively,whereas,the corresponding concentrations of ACM-A were 10.795,12.796 and 10.135 mg·L^-1.CONCLUSION The prepared ACM-SLN was stable and there was significantly increase for the drug concentration in mice liver after iv administration of ACM-SLN comparing with ACM-A solution.