Synergistic permeability enhancing effect of lysophospholipids and fatty acids on lipid membranes.
The permeability-enhancing effects of the two surfactants, 1-palmitoyl-2-lyso-sn-gycero-3-phosphocholine (lysoPPC) and palmitic acid (PA), on lipid membranes that at physiological temperatures are in the gel, fluid, and liquid-ordered phases were determined using the concentration-dependent self-quenching properties of the hydrophilic marker, calcein. Adding lysoPPC to lipid membranes in the gel-phase induced a time-dependent calcein release curve that can be described by the sum of two exponentials, whereas PA induces a considerably more complex release curve. However, when lysoPPC and PA were added simultaneously in equimolar concentrations, a dramatic synergistic permeability-enhancing effect was observed. In contrast, when both lysoPPC and PA are added to liposomal membranes that are in the fluid or liquid-ordered phases, no effect on the transmembrane permeation of calcein was observed.
Davidsen
Jesper
J
Department of Pharmaceutics, The Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Mouritsen
Ole G
OG
Jørgensen
Kent
K
D004337:Drug Carriers; D016503:Drug Delivery Systems; D004357:Drug Synergism; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005782:Gels; D066298:In Vitro Techniques; D008244:Lysophosphatidylcholines / Q000008:administration & dosage / Q000494:pharmacology*; D008563:Membrane Lipids / Q000737:chemistry*; D019308:Palmitic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000494:pharmacology
C089215:1-palmitoyl-2-lysophosphatidylcholine; D004337:Drug Carriers; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005782:Gels; D008244:Lysophosphatidylcholines; D008563:Membrane Lipids; D013501:Surface-Active Agents; D019308:Palmitic Acid; C007740:fluorexon