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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.

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.

journal_name

Int J Pharm

journal_title

International journal of pharmaceutics

authors

Akhter A,Hayashi Y,Sakurai Y,Ohga N,Hida K,Harashima H

doi

10.1016/j.ijpharm.2013.07.068

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

195-201

issue

1

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(13)00694-7

journal_volume

456

pub_type

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