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Zhang, Zhiwen; Bu, Huihui; Gao, Zhiwei; Huang, Yan; Gao, Fang; Li, Yaping
International journal of pharmaceutics, 07/2010, Letnik: 394, Številka: 1Journal Article
Simvastatin (SV), a cholesterol-lowering agent, has been widely used in the treatment of hypercholesterolemia, dyslipidemia and coronary heart disease, but SV shows the low oral bioavailability due to its poor aqueous solubility and extensive metabolism by cytochrome-3A system in intestinal guts and liver. In this work, SV loaded lipid nanoparticles (SLNs) with different components were designed to enhance its oral bioavailability, and the plasma concentration of SV and its active metabolite (simvastatin acid, SVA) was determined by LC–MS–MS method. The experimental results showed that SLNs were spherical nano-sized particles with high encapsulation efficiency (>95%). The in situ intestinal absorption indicated that the absorption of SLNs was greatly improved compared with that of free SV, and the absorption was changed with the site of the intestinal segments. SLNs could be uptaken into the enterocytes through both clathrin and caveolae mediated endocytosis pathways. The oral bioavailability of SV after its incorporation into the lipid nanoparticles was improved by 3.37-fold for SLNs I and 2.55-fold for SLNs II compared with that from free SV in rats, and that of the SVA was significantly enhanced as well. As a result, lipid nanoparticles could be a promising delivery system to enhance the oral bioavailability of simvastatin.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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