Synthesis and Evaluation of Stearylated Hyaluronic Acid for the Active Delivery of Liposomes to Liver Endothelial Cells

概要

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Hyaluronic acid (HA) is a naturally-occurring ligand that can be useful for targeting liver endothelial cells. We describe herein the development of a new HA-lipid conjugate for the efficient delivery of liposomes to liver endothelial cells. When free HA coated cationic liposomes were injected into mice, their accumulation in the liver was significantly decreased depending on the content of free HA, while accumulation in the lung was not significantly changed. When cationic liposomes modified with HA-stearylamine (HA-SA conjugate) were injected in mice, liver accumulation was increased depending on the amount of HA-SA conjugate and accumulation in the lung was drastically reduced, compared to non-modified liposomes. Confocal imaging analyses showed that HA-SA modified liposomes were accumulated to a greater extent along with blood vessels than non-modified liposomes, suggesitng that HA-SA modified liposomes are distributed in endothelial cells in the liver. Collectively, these findings indicate that an HA-SA conjugate is a useful material that can be used to modify liposomes and for delivering bioactive liposomal cargoes to liver endothelial cells.