Chem. Pharm. Bull. 54(1) 68—71 (2006)

docosahexaenoic acid (DHA, 22:6) and eicosapentaenoic acid (EPA, 20:5), is linked to the prevention of diseases such as cancer and heart disease, and is needed for neurological and brain development. We have recently attempted to use these functional fatty acids as an absorption enhancer and have reported that intestinal absorption of insulin and vancomycin increase when administered with these fatty acids in a water-in-oil-in-water (W/O/W) multiple emulsion. We have also reported that the enhancement effect of DHA and EPA is much stronger than that of other unsaturated fatty acids, such as oleic acid, and does not induce any tissue damage. Although the mechanism responsible remains unclear, the effect of DHA and EPA may be attributed to their actions on the transcellular pathway rather than the paracellular pathway because the tissue membrane resistance values do not change with treatment. Administering an emulsion into the intestinal lumen should cause the fatty acids contained in the emulsion to be taken up readily into the lipid bilayer of the intestinal mucosa, causing a change in the lipid packing. In general, the structural change in the lipid bilayer is a critical factor for transcellular pathway. There are many reports that perturbation of the lipid-packing order increases drug permeability. In addition, recent studies have shown that altering membrane fluidity influences carrier-mediated transport, such as P-glycoprotein-mediated efflux. Because DHA and EPA have multiple double bonds, they should change the lipid packing drastically. Such changes in the lipid bilayer structure should cause modifications of the biological membrane function, and it is important to identify the action of fatty acids on the lipid bilayer structure. We investigated changes in the physical properties of the lipid bilayer by treating model bilayers with various fatty acids such as stearic acid (SA, 18:0), oleic acid (OA, 18:1), EPA, and DHA. Because the plasma membrane structure is too complex, we used dipalmitoylphosphatidylcholine (DPPC) liposomes as a model of the lipid bilayer. We assessed the structural changes in the lipid bilayer induced by fatty acids by measuring changes in the phase transition temperature, fluorescence anisotropy, and detergent insolubility. To evaluate whether fatty acids incorporated in the formulation act successfully on the lipid bilayer, we also performed the same experiments using a W/O/W multiple emulsion containing fatty acids.