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已发表论文

增强环孢素 A 的口服生物利用度：各种纳米药物输送系统的比较

 

Authors Wang K, Qi JP, Weng TF, Tian ZQ, Lu Y, Hu KL, Yin ZN, Wu W

Published Date October 2014 Volume 2014:9(1) Pages 4991—4999

DOI http://dx.doi.org/10.2147/IJN.S72560

Received 11 August 2014, Accepted 12 September 2014, Published 28 October 2014

Approved for publication by Dr Lei Yang

Abstract: 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®, 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®. 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.
Keywords: cyclosporine A, PLGA nanoparticle, nanostructured lipid carrier, self-microemulsifying drug-delivery systems, bioavailability






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