Mechanistic studies on surfactant-induced membrane permeability enhancement

Purpose. To gain some mechanistic understanding of surfactant-induced membr ane permeabilization and identify a surfactant physical property that can b e used as a predictor for intestinal membrane permeability enhancement. Methods. The maximum surface pressures (pi(CMC)) Of series of anionic and n on-ionic surfactants as indicators of surface activity were determined usin g a bubble surface tensiometer, and related to in vivo intestinal membrane permeability and acute damage data of the same surfactants from a previous work. Phospholipid bilayers with constant surface pressures and monolayers with different surface pressures were used as model membranes to systematic ally study membrane permeability enhancement and membrane penetration of su rfactants at different concentrations. Results. Surfactants that did not permeabilize or acutely damage the intest inal wall generally exhibited a pi(CMC) < 25 dyne/cm. Permeability enhancem ent and acute damage increased as nc,cic increased beyond 25 dyne/cm. This critical threshold value at around 25 dynes/cm was also observed with in vi tro experiments using phospholipid vesicles and monolayers. Data support th e hypothesis that the threshold phenomenon originates from the interfacial tension at the membrane/water interface, which controls the surface adsorpt ion process of surfactant molecules onto the membrane. Conclusions. For a surfactant to permeabilize and acutely damage the intest inal wall, it must exhibit a surface pressure of greater than 25 dynes/cm. This threshold value is related to an intrinsic property, surface pressure, of the phospholipid membranes. Since the surfactant surface pressure is a property of the surfactant monomer, partition of the surfactant monomer, no t the micelle, into the membrane is an obligate step in membrane permeabili zation. Above the surfactant critical micelle concentration, CMC, micelles may act as a depot to continuously replace aqueous surfactant monomers take n up by the membrane. For some surfactants above CMC, sufficient number of monomers can partition into the membrane to cause solubilization of membran e lipids in surfactant micelles.