Enhanced oral bioavailability of cyclosporine A by liposomes containing a bile salt

Abstract

Peipei Guan1, Yi Lu1, Jianping Qi1, Mengmeng Niu1, Ruyue Lian1, Fuqiang Hu2, Wei Wu11School of Pharmacy, Fudan University, Shanghai, People's Republic of China; 2School of Pharmacy, Zhejiang University, Hangzhou, People's Republic of ChinaAbstract: The main purpose of this study was to evaluate liposomes containing a bile salt, sodium deoxycholate (SDC), as oral drug delivery systems to enhance the oral bioavailability of the poorly water-soluble and poorly permeable drug, cyclosporine A (CyA). Liposomes composed of soybean phosphatidylcholine (SPC) and SDC were prepared by a thin-film dispersion method followed by homogenization. Several properties of the liposomes including particle size, polydispersity index, and entrapment efficiency were characterized. The in vitro release of CyA from these liposomes was less than 5% at 12 hours as measured by a dynamic dialysis method. The pharmacokinetic results in rats showed improved absorption of CyA in SPC/SDC liposomes, compared with CyA-loaded conventional SPC/cholesterol (Chol) liposomes and microemulsion-based Sandimmune Neoral®. The relative oral bioavailability of CyA-loaded SPC/SDC and SPC/Chol liposomes was 120.3% and 98.6%, respectively, with Sandimmun Neoral as the reference. The enhanced bioavailability of CyA was probably due to facilitated absorption by the liposomes containing SDC rather than improved release rate.Keywords: liposomes, bile salt, sodium deoxycholate, cyclosporine A, oral bioavailability