School of Pharmacy, Fudan University, Shanghai, People's Republic of China.
Int J Nanomedicine. 2011;6:965-74. doi: 10.2147/IJN.S19259. Epub 2011 May 4.
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.
本研究的主要目的是评估含有胆汁盐脱氧胆酸钠（SDC）的脂质体作为口服药物传递系统，以提高脂溶性和渗透性差的药物环孢素 A（CyA）的口服生物利用度。采用薄膜分散法制备由大豆卵磷脂（SPC）和 SDC 组成的脂质体，然后进行匀浆处理。对脂质体的粒径、多分散指数和包封效率等性质进行了表征。通过动态透析法测定，脂质体中 CyA 的体外释放在 12 小时内小于 5%。大鼠的药代动力学结果表明，与载有 CyA 的常规 SPC/胆固醇（Chol）脂质体和基于微乳液的 Sandimmune Neoral（®）相比，SPC/SDC 脂质体中 CyA 的吸收得到改善。载有 SPC/SDC 和 SPC/Chol 脂质体的 CyA 的相对口服生物利用度分别为 120.3%和 98.6%，以 Sandimmune Neoral 为参照。CyA 的生物利用度提高可能是由于含有 SDC 的脂质体促进了吸收，而不是释放速率的提高。
