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Enhancement of oral bioavailability of cyclosporine A: comparison of various nanoscale drug-delivery systems

文献类型： 外文期刊

作者： Wang, Kai 1 ; Qi, Jianping 1 ; Weng, Tengfei 1 ; Tian, Zhiqiang 1 ; Lu, Yi 1 ; Hu, Kaili 4 ; Yin, Zongning 2 ; Wu, Wei 1 ;

作者机构： 1.Fudan Univ, Sch Pharm, Key Lab Smart Drug Delivery, Minist Educ, Shanghai 201203, Peoples R China

2.Sichuan Univ, West China Sch Pharm, Chengdu 610064, Sichuan, Peoples R China

3.Chinese Acad Trop Agr Sci, Hainan Prov Engn Res Ctr Blumea Balsamifera, Trop Crops Genet Resources Inst, Danzhou, Hainan, Peoples R China

4.Shanghai Univ Tradit Chinese Med, Murad Res Ctr Modernize

关键词： cyclosporine A;PLGA nanoparticle;nanostructured lipid carrier;self-microemulsifying drug-delivery systems;bioavailability

期刊名称：INTERNATIONAL JOURNAL OF NANOMEDICINE （ 影响因子：6.4； 五年影响因子：6.761 ）

ISSN： 1178-2013

年卷期： 2014 年 9 卷

页码：

收录情况： SCI

摘要： A variety of nanoscale delivery systems have been shown to enhance the oral absorption of poorly water-soluble and poorly permeable drugs. However, the performance of these systems has seldom been evaluated simultaneously. The aim of this study was to compare the bioavailability enhancement effect of lipid-based nanocarriers with poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) to highlight the importance of the lipid composition, with cyclosporine A (CyA) as a model drug. CyA-loaded PLGA NPs, nanostructured lipid carriers (NLCs), and self-microemulsifying drug-delivery systems (SMEDDS) were prepared. The particle size of PLGA NPs (182.2 +/- 12.8 nm) was larger than that of NLCs (89.7 +/- 9.0 nm) and SMEDDS (26.9 +/- 1.9 nm). All vehicles are charged negatively. The entrapment efficiency of PLGA NPs and NLCs was 87.6%+/- 1.6% and 80.3%+/- 0.6%, respectively. In vitro release tests indicated that the cumulative release of CyA was lower than 4% from all vehicles, including Sandimmun Neoral (R), according to the dialysis method. Both NLCs and SMEDDS showed high relative oral bioavailability, 111.8% and 73.6%, respectively, after oral gavage administration to beagle dogs, which was not statistically different from commercial Sandimmun Neoral (R). However, PLGA NPs failed to achieve efficient absorption, with relative bioavailability of about 22.7%. It is concluded that lipid-based nanoscale drug-delivery systems are superior to polymeric NPs in enhancing oral bioavailability of poorly water-soluble and poorly permeable drugs.

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