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The potential role of fucosylated cationic liposome/NFκB decoy complexes in the treatment of cytokine-related liver disease

Paper ID Volume ID Publish Year Pages File Format Full-Text
11522 746 2007 8 PDF Available
Title
The potential role of fucosylated cationic liposome/NFκB decoy complexes in the treatment of cytokine-related liver disease
Abstract

Cytokine production by Kupffer cells, which is regulated by NFκB, causes severe liver injury in endotoxin syndrome. NFκB decoy has been reported to inhibit NFκB-mediated transcription. The purpose of this study is to inhibit LPS-induced cytokine production by Kupffer cell-targeted delivery of NFκB decoy using fucosylated cationic liposomes (Fuc-liposomes). Cholesten-5-yloxy-N-{4-[(1-imino-2-l-thiofucosyl-ethyl)-amino] butyl-}formamide (Fuc-C4-Chol) was synthesized to prepare Fuc-liposomes. Tissue accumulation, intrahepatic distribution and serum cytokine concentrations were investigated after intravenous injection of Fuc-liposomes/NFκB decoy complexes. Intravenously injected Fuc-liposome complexes rapidly and highly accumulated in the liver while little naked NFκB decoy accumulated in the liver. An intrahepatic distribution study showed that Fuc-liposome complexes are mainly taken up by non-parenchymal cells. The liver accumulation of Fuc-liposome complexes was inhibited by GdCl3 pretreatment, which selectively inhibited Kupffer cell uptake. This result suggested that Kupffer cells contribute to liver accumulation. TNFα, IFNγ, ALT and AST serum levels in LPS-infected mice were significantly attenuated by treatment with Fuc-liposome complexes compared with naked NFκB decoy. Fuc-liposome complexes also reduced the amount of activated NFκB in the liver nuclei. Fuc-liposomes would be a useful carrier for Kupffer cell-selective delivery of NFκB decoy by intravenous injection.

Keywords
Fucosylated cationic liposome; Gene delivery; Gene therapy; Targeting; NFκB decoy; Kupffer cell
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The potential role of fucosylated cationic liposome/NFκB decoy complexes in the treatment of cytokine-related liver disease
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 28, Issue 3, January 2007, Pages 532–539
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us