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 for this work

128 Citations (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.

Original language	English
Journal	Biochimica et Biophysica Acta - Biomembranes
Volume	1609
Issue number	1
Pages (from-to)	95-101
Number of pages	7
ISSN	0005-2736
DOIs	https://doi.org/10.1016/S0005-2736(02)00659-4
Publication status	Published - 10 Jan 2003

Keywords

Drug delivery
Enhancer
Fatty acid
Liposome
Lyso-phospholipid
Membrane
Permeability
Phospholipase A
Surfactant

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/S0005-2736(02)00659-4

Cite this

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.

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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