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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
| 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)
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Submitter: 原島 秀吉
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