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A liposomal delivery system that targets liver endothelial cells based on a new peptide motif present in the ApoB-100 sequence

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Title: A liposomal delivery system that targets liver endothelial cells based on a new peptide motif present in the ApoB-100 sequence
Authors: Akhter, Afsana Browse this author
Hayashi, Yasuhiro Browse this author →KAKEN DB
Sakurai, Yu Browse this author
Ohga, Noritaka Browse this author →KAKEN DB
Hida, Kyoko Browse this author →KAKEN DB
Harashima, Hideyoshi Browse this author →KAKEN DB
Keywords: ApoB-100 sequence
CSPG
LDL receptor
Liver endothelial cell
RLTR peptide
KLGR peptide
Issue Date: 1-Nov-2013
Publisher: Elsevier science bv
Journal Title: International journal of pharmaceutics
Volume: 456
Issue: 1
Start Page: 195
End Page: 201
Publisher DOI: 10.1016/j.ijpharm.2013.07.068
PMID: 23933440
Abstract: Liver dysfunction is associated with a variety of liver diseases, including viral or alcoholic hepatitis, fibrosis, cirrhosis, and portal hypertension. A targeted drug delivery system would be very useful in the treatment of these diseases. We herein describe the development of a system comprised of a new peptide-lipid conjugate for the efficient delivery of molecules to LEC. The RLTRKRGLK sequence (3359-3367), which mediates the association of LDL with arterial CSPG and an LDL receptor, was utilized as a ligand for achieving this goal. The peptide modified PEG-LPs (RLTR-PEG-LPs) were efficiently taken up by primary liver endothelial cells (liver ECs) and other types of cells. In vivo biodistribution and confocal microscopy analysis showed that RLTR-PEG-LPs became widely accumulated in LECs within a short time. Distribution of RLTR-PEG-LPs was greatly reduced with a pretreatment of unlabeled RLTR-PEG-LPs, not cationic LPs, indicating that the sequence is important for LECs. The findings indicate that a reverse sequence of RLTR (KLGR) modified PEG-LPs (KLGR-PEG-LP) did the same pattern compared with RLTR-PEG- LPs, suggesting that the RKR or RXXR sequence might be essential for LECs targeting. Collectively RLTR-PEG-LPs and KLGR-PEG-LPs have the potential for delivering drugs to LECs. (C) 2013 Elsevier B.V. All rights reserved.
Type: article (author version)
URI: http://hdl.handle.net/2115/54790
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 原島 秀吉

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