Digestion of lipid micelles leads to increased membrane permeability

Research output: Contribution to journalArticlepeer-review


Lipid-based drug carriers are an attractive option to solubilise poorly water soluble therapeutics. Previously, we reported that the digestion of a short tail PC lipid (2C6PC) by the PLA2 enzyme has a significant effect on the structure and stability of the micelles it forms. Here, we studied the interactions of micelles of varying composition representing various degrees of digestion with a model ordered (70 mol% DPPC & 30 mol% cholesterol) and disordered (100% DOPC) lipid membrane. Micelles of all compositions disassociated when interacting with the two different membranes. As the percentage of digestion products (C6FA and C6LYSO) in the micelle increased, the disassociation occurred more rapidly. The C6FA inserts preferentially into both membranes. We find that all micelle components increase the area per lipid, increase the disorder and decrease the thickness of the membranes, and the 2C6PC lipid molecules have the most significant impact. Additionally, there is an increase in permeation of water into the membrane that accompanies the insertion of C6FA into the DOPC membranes. We show that the natural digestion of lipid micelles result in molecular species that can enhance the permeability of lipid membranes that in turn result in an enhanced delivery of drugs.

Original languageEnglish
Pages (from-to)2642-2653
Number of pages12
Issue number5
Publication statusPublished - 2 Jan 2024


  • Micelles
  • Lipid Bilayers/chemistry
  • Water/chemistry
  • Permeability
  • Digestion


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