Study on preparation conditions for polylactide nanoparticles loaded cyclosporine A and its oral bioavailability in rats

目的研究环孢素A聚乳酸纳米粒胶体(CyA-NP)的制备处方与工艺,并以新山地明(Neoral)为参比制剂,进行相对生物利用度考察.方法以溶剂-非溶剂法制备CyA-NP,用HPLC法测定全血中的药物浓度,计算胶体的生物利用度.结果胶体中的纳米粒均匀圆整,粒径为57.5 nm,药物回收率大于90%.CyA-NP的AUC0-72为29.06 mg·h·L-1,Neoral的AUC0-72为28.59 mg·h·L-1,与Neoral相比,CyA-NP的相对生物利用度为101.6%,峰浓度较小(P<0.05),吸收较慢(P<0.05),消除亦较慢(P<0.1).结论以溶剂-非溶剂法可以简便制得CyA-NP,其大鼠相对生物利用度与Neoral相比无显著性差异,有望成为Neoral的代用品.To develop a less toxic alternative for sandimmun neoral (Neoral). To study the preparation conditions and to compare its pharmacokinetic characteristics with Neoral.Polylactide nanoparticles loaded cyclosporine A was prepared by solvent-nonsolvent method. Polylactide nanoparticles were administered by oral in a dosage of 15 mg.kg-1. The CyA concentration in whole blood sample was determined by HPLC.The quantities of CyA, PLA and volume of acetone added had significant influence on the NP diameters. Under proper condition, the nanoparticles with diameters of 57.5 nm were obtained. The relative bioavailability in rats was 101.6%, with a smaller absorption rate (P < 0.05) and a smaller elimination rate (P < 0.1).The nanoparticles (diamater < 100 nm) with relative high bioavailability were prepared using solvent-nonsolvent method. It is suitable for further study.国家高技术研究发展计划(863计划)PubMed中文核心期刊要目总览(PKU)中国科学引文数据库(CSCD)0168-713