Enhanced oral bioavailability of cyclosporine A by liposomes containing a bile salt
Enhanced oral bioavailability of cyclosporine A by liposomes containing a bile salt
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DOI：
10.2147/ijn.s19259
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发表时间：
2011-01-01
影响因子：
8
通讯作者：
Wu, Wei
中科院分区：
文献类型：
--
作者：
Guan, Peipei;Lu, Yi;Wu, Wei
本研究的主要目的是评估含有胆盐脱氧胆酸钠（SDC）的脂质体作为口服给药系统，以提高水溶性和渗透性差的药物环孢素A（CyA）的口服生物利用度。由大豆磷脂酰胆碱（SPC）和SDC组成的脂质体通过薄膜分散法制备，随后进行均质化。对脂质体的几个特性，包括粒径、多分散指数和包封率进行了表征。通过动态透析法测定，CyA从这些脂质体中的体外释放量在12小时内小于5%。大鼠体内的药代动力学结果显示，与载CyA的常规SPC/胆固醇（Chol）脂质体和基于微乳的新山地明（Sandimmune Neoral®）相比，CyA在SPC/SDC脂质体中的吸收有所改善。以新山地明为参照，载CyA的SPC/SDC和SPC/Chol脂质体的相对口服生物利用度分别为120.3%和98.6%。CyA生物利用度的提高可能是由于含有SDC的脂质体促进了吸收，而非释放速率的提高。
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 (R). 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.