Design of a dual-ligand system using a specific ligand and cell penetrating peptide, resulting in a synergistic effect on selectivity and cellular uptake

In this study, a dual-ligand liposomal system comprised of a specific ligand and a cell penetrating peptide (CPP) is described to enhance selectivity and cellular uptake. Dual-ligand PEGylated liposomes were prepared by modifying the end of the PEG with an NGR motif peptide, followed by a surface co...

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Bibliographic Details
Published in:International journal of pharmaceutics 2010-08, Vol.396 (1), p.143-148
Main Authors: Takara, Kazuhiro, Hatakeyama, Hiroto, Ohga, Noritaka, Hida, Kyoko, Harashima, Hideyoshi
Format: Article
Language:English
Subjects:
Active targeting
Animals
Arginine - chemistry
Biological and medical sciences
Biological Transport
CD13 Antigens - metabolism
Cell Membrane Permeability
Cell penetrating peptide
Cells, Cultured
Chemistry, Pharmaceutical
Drug Carriers
Drug Compounding
Dual-ligand
Endothelial Cells - metabolism
General pharmacology
Ligands
Liposomes
Medical sciences
Melanoma - blood supply
Mice
Mice, Nude
Nanotechnology
NGR
Oligopeptides - chemistry
Oligopeptides - metabolism
Particle Size
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Polyethylene Glycols - chemistry
Stearates - chemistry
Technology, Pharmaceutical - methods
Tumor endothelial cells
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Summary:In this study, a dual-ligand liposomal system comprised of a specific ligand and a cell penetrating peptide (CPP) is described to enhance selectivity and cellular uptake. Dual-ligand PEGylated liposomes were prepared by modifying the end of the PEG with an NGR motif peptide, followed by a surface coating of the liposomes with stearylated oligoarginine (STR-RX). The NGR motif recognizes CD13, a marker protein located on tumor endothelial cells. A suitable number of RX units was determined to be R4, since it can be masked by the PEG aqueous layer. Although no enhanced cellular uptake was observed when a single modification of PEGylated liposomes with either NGR- or STR-R4 was used, the dual-modification with NGR and STR-R4 stimulated uptake of PEGylated liposomes by CD13 positive cells, and this uptake was superior to that obtained by PEG-unmodified liposomes modified with STR-R4. The dual-ligand system shows a synergistic effect on cellular uptake. Collectively, the dual-ligand system promises to be useful in the development efficient and specific drug delivery systems.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2010.05.002