Secreted phospholipase A2 as a new enzymatic trigger mechanism for localised liposomal drug release and absorption in diseased tissue

Jesper Davidsen; Kent Jørgensen; Thomas L. Andresen; Ole G. Mouritsen

doi:10.1016/S0005-2736(02)00659-4

Secreted phospholipase A₂ as a new enzymatic trigger mechanism for localised liposomal drug release and absorption in diseased tissue

Jesper Davidsen, Kent Jørgensen^*, Thomas L. Andresen, Ole G. Mouritsen

^*Corresponding author af dette arbejde

128 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Biochimica et Biophysica Acta - Biomembranes
Vol/bind	1609
Udgave nummer	1
Sider (fra-til)	95-101
Antal sider	7
ISSN	0005-2736
DOI	https://doi.org/10.1016/S0005-2736(02)00659-4
Status	Udgivet - 10 jan. 2003

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Citationsformater

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. et al.

I: Biochimica et Biophysica Acta - Biomembranes, Bind 1609, Nr. 1, 10.01.2003, s. 95-101.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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AU - Mouritsen, Ole G.

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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.

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