کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1425728 | 986777 | 2010 | 8 صفحه PDF | دانلود رایگان |

Human serum albumin (HSA), a non-glycosylated protein, is widely employed as carrier for drug delivery systems. A series of recombinant, mannosylated-HSA mutants (Man-rHSAs: D63N, A320T and D494N) and their triple mutant (TM-rHSA: D63N/A320T/D494N) were prepared, that can be selectively delivered to the liver via mannose receptor (MR) on the liver non-parenchymal cells. A pharmacokinetic analysis of 111In-Man-rHSAs in mice showed that they were rapidly cleared from the blood circulation, and were largely taken up by the liver rapidly in the order: TM-rHSA > D494N ≫ A320T = D63N, consistent with their degree of mannosylation. In vivo competition experiments with an excess amount of chemically modified Man-BSA or mannan suggested that the hepatic uptake of TM-rHSA was selectively mediated by MR on Kupffer cells. Lastly, a TM-rHSA–NO conjugate, S-nitrosylated TM-rHSA, effectively delivered NO to the liver and then exhibited a significant inhibitory effect against hepatic ischemia/reperfusion injury model rats, accompanied by the induction of heme oxygenase-1.
Genetically engineered mannosylated-rHSA has the potential for use as a versatile carrier for liver-selective therapeutics, such as NO.Figure optionsDownload as PowerPoint slide
Journal: Journal of Controlled Release - Volume 145, Issue 1, 1 July 2010, Pages 9–16