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

Research output: Contribution to journalJournal articleResearchpeer-review

140 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 languageEnglish
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1609
Issue number1
Pages (from-to)95-101
Number of pages7
ISSN0005-2736
DOIs
Publication statusPublished - 10 Jan 2003

Keywords

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

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