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

作者：Akhter Afsana; Hayashi Yasuhiro; Sakurai Yu; Ohga Noritaka; Hida Kyoko; Harashima Hideyoshi^*

来源：International Journal of Pharmaceutics, 2013, 456(1): 195-201.

DOI：10.1016/j.ijpharm.2013.07.068

• ApoB-100 sequence
• CSPG
• LDL receptor
• Liver endothelial cell
• RLTR peptide
• KLGR peptide

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.

• 出版日期2013-11-1