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Updated: Apr 11, 2026

A Liposome Membrane Permeability Assay for Investigating the Effects of Phosphatidylinositol Phosphate Groups on Membranotropic Action of Venom PLA2
10:31

A Liposome Membrane Permeability Assay for Investigating the Effects of Phosphatidylinositol Phosphate Groups on Membranotropic Action of Venom PLA2

Published on: September 26, 2025

653

Enzymatic action of phospholipase A₂ on liposomal drug delivery systems

Anders H Hansen1, Ole G Mouritsen1, Ahmad Arouri1

  • 1MEMPHYS-Center for Biomembrane Physics, Department of Physics, Chemistry, and Pharmacy, University of Southern Denmark, Odense, Denmark; The Lundbeck Foundation Nanomedicine Research Center for Cancer Stem Cell Targeting Therapeutics (NanoCAN), University of Southern Denmark, Odense, Denmark.

International Journal of Pharmaceutics
|June 10, 2015
PubMed

Insights

Secretory phospholipase A2 (sPLA2) enzyme activity on liposomes is sensitive to lipid composition and temperature, impacting drug delivery. Understanding these factors optimizes sPLA2-triggered liposomal drug release in tumors.

Area of Science:

  • Biochemistry
  • Materials Science
  • Drug Delivery

Background:

  • Overexpression of secretory phospholipase A2 (sPLA2) in tumors enables enzyme-triggered drug carrier unloading.
  • Liposome composition, drug loading, and tumor microenvironment effects on sPLA2 activity require further investigation for targeted drug delivery.

Purpose of the Study:

  • To physico-chemically characterize sPLA2-assisted liposome breakdown for drug delivery.
  • To investigate the influence of temperature, lipid concentration, enzyme concentration, and drug loading on liposome hydrolysis.
  • To assess sPLA2 sensitivity to liposome composition, including lipid acyl-chain length and surface charge.

Main Methods:

  • Utilized dye-release assays to study liposome breakdown under physiologically relevant conditions.
  • Investigated 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes with snake venom sPLA2.
  • Examined binary lipid mixtures of phosphatidylcholine (PC) and phosphatidylglycerol (PG) with varying acyl chains (C14, C16).

Main Results:

  • Increased temperature (36-41°C) primarily reduced enzyme lag-time, with minor effects on lipid hydrolysis rate.
  • Enzyme lag-time showed an inverse dependency on the lipid-to-enzyme ratio.
  • Drug encapsulation altered liposome hydrolysis profiles.
  • Human sPLA2 activity was highly sensitive to phospholipid acyl-chain length and liposome surface charge density.

Conclusions:

  • Physico-chemical parameters significantly influence sPLA2-mediated liposome hydrolysis.
  • Findings provide a basis for optimizing sPLA2-susceptible liposomal formulations for targeted cancer therapy.
  • This research aids in predicting liposome hydrolysis in vivo for improved drug delivery efficacy.
Keywords:
AnticancerBio-responsive liposomesDrug delivery systemDye-release assayPhospholipase A(2) enzymeTriggered drug release

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