Secreted phospholipase A2 as a new enzymatic trigger mechanism for localised liposomal drug release and absorption in diseased tissue |
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Authors: | Jesper Davidsen Thomas L Andresen |
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Institution: | a Department of Pharmaceutics, The Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100 Copenhagen Ø, Denmark b LiPlasome Pharma A/S, Department of Chemistry, Technical University of Denmark, Building 207, DK-2800 Lyngby, Denmark c Physics Department, MEMPHYS-Center for Biomembrane Physics, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark |
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Abstract: | Polymer-coated liposomes can act as versatile drug-delivery systems due to long vascular circulation time and passive targeting by leaky blood vessels in diseased tissue. We present an experimental model system illustrating a new principle for improved and programmable drug-delivery, which takes advantage of an elevated activity of secretory phospholipase A2 (PLA2) at the diseased target tissue. The secretory PLA2 hydrolyses a lipid-based proenhancer in the carrier liposome, producing lyso-phospholipids and free fatty acids, which are shown in a synergistic way to lead to enhanced liposome destabilization and drug release at the same time as the permeability of the target membrane is enhanced. Moreover, the proposed system can be made thermosensitive and offers a rational way for developing smart liposome-based drug delivery systems. This can be achieved by incorporating specific lipid-based proenhancers or prodestabilisers into the liposome carrier, which automatically becomes activated by PLA2 only at the diseased target sites, such as inflamed or cancerous tissue. |
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Keywords: | Drug delivery Liposome Phospholipase A2 Permeability Membrane Surfactant Enhancer Lyso-phospholipid Fatty acid |
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