Secreted phospholipase A2 as a new enzymatic trigger mechanism for localised liposomal drug release and absorption in diseased tissue
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Secreted phospholipase A2 as a new enzymatic trigger mechanism for localised liposomal drug release and absorption in diseased tissue. / Davidsen, Jesper; Jørgensen, Kent; Andresen, Thomas L.; Mouritsen, Ole G.
In: Biochimica et Biophysica Acta - Biomembranes, Vol. 1609, No. 1, 10.01.2003, p. 95-101.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Secreted phospholipase A2 as a new enzymatic trigger mechanism for localised liposomal drug release and absorption in diseased tissue
AU - Davidsen, Jesper
AU - Jørgensen, Kent
AU - Andresen, Thomas L.
AU - Mouritsen, Ole G.
PY - 2003/1/10
Y1 - 2003/1/10
N2 - 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.
AB - 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.
KW - Drug delivery
KW - Enhancer
KW - Fatty acid
KW - Liposome
KW - Lyso-phospholipid
KW - Membrane
KW - Permeability
KW - Phospholipase A
KW - Surfactant
UR - http://www.scopus.com/inward/record.url?scp=0037427971&partnerID=8YFLogxK
U2 - 10.1016/S0005-2736(02)00659-4
DO - 10.1016/S0005-2736(02)00659-4
M3 - Journal article
C2 - 12507763
AN - SCOPUS:0037427971
VL - 1609
SP - 95
EP - 101
JO - B B A - Biomembranes
JF - B B A - Biomembranes
SN - 0005-2736
IS - 1
ER -
ID: 230986431