Guo J, Ping Q, Chen Y
Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
Int J Pharm. 2001 Mar 23;216(1-2):17-21. doi: 10.1016/s0378-5173(00)00680-3.
The present study was undertaken to investigate the incorporation of lipophilic polypeptide, cyclosporin A (CsA) into lecithin vesicular system and to compare its pharmacokinetics behavior with Sandimmun Neoral (CsA-NEO). Lecithin vesicles of cyclosporin A (CsA-VES) were prepared by the rotary evaporation method, treated further with sonication. Studies were carried out to characterize the vesicles on physical properties, content, entrapment efficiency, particle size, polydispersity and Zeta potential. Pharmacokinetic behaviors were studied in rabbits at dose of 30 mg/kg. Results showed CyA vesicles were spherical particles, with content of 3.137+/-0.060% mg/ml, entrapment efficiency of 98.91+/-0.80%, particle size of 63.89+/-4.75 nm, polydispersity of 43.2+/-6.1% and Zeta potential of -13 mV. The best model fitting experimental data was a two-compartment open model with first-order kinetics. The relative bioavailability of CsA-VES versus CsA-NEO was 105+/-21% (n=6) and statistical analysis demonstrated both preparations were bioequivalent. In conclusion, lecithin vesicles are promising carriers in the oral delivery of CsA, considering their absorption enhancement effect and low-toxic property.
本研究旨在探讨亲脂性多肽环孢素A（CsA）掺入卵磷脂囊泡系统，并将其药代动力学行为与新山地明（CsA-NEO）进行比较。采用旋转蒸发法制备环孢素A卵磷脂囊泡（CsA-VES），并进一步进行超声处理。对囊泡的物理性质、含量、包封率、粒径、多分散性和Zeta电位进行了表征研究。以30mg/kg的剂量在兔体内研究药代动力学行为。结果显示，环孢素A囊泡为球形颗粒，含量为3.137±0.060%mg/ml，包封率为98.91±0.80%，粒径为63.89±4.75nm，多分散性为43.2±6.1%，Zeta电位为-13mV。对实验数据拟合效果最好的模型是具有一级动力学的二室开放模型。CsA-VES相对于CsA-NEO的相对生物利用度为105±21%（n=6），统计分析表明两种制剂具有生物等效性。总之，考虑到卵磷脂囊泡的吸收增强作用和低毒性，其有望成为环孢素A口服给药的载体。
