Mechanistic studies on surfactant-induced membrane permeability enhancement.
OBJECTIVE
To gain some mechanistic understanding of surfactant-induced membrane permeabilization and identify a surfactant physical property that can be used as a predictor for intestinal membrane permeability enhancement.


METHODS
The maximum surface pressures (piCMC) of series of anionic and non-ionic surfactants as indicators of surface activity were determined using 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 systematically study membrane permeability enhancement and membrane penetration of surfactants at different concentrations.


RESULTS
Surfactants that did not permeabilize or acutely damage the intestinal wall generally exhibited a piCMC < 25 dyne/cm. Permeability enhancement and acute damage increased as piCMC increased beyond 25 dyne/cm. This critical threshold value at around 25 dynes/cm was also observed with in vitro experiments using phospholipid vesicles and monolayers. Data support the hypothesis that the threshold phenomenon originates from the interfacial tension at the membrane/water interface, which controls the surface adsorption process of surfactant molecules onto the membrane.


CONCLUSIONS
For a surfactant to permeabilize and acutely damage the intestinal 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, not the micelle, into the membrane is an obligate step in membrane permeabilization. Above the surfactant critical micelle concentration, CMC, micelles may act as a depot to continuously replace aqueous surfactant monomers taken up by the membrane. For some surfactants above CMC, sufficient number of monomers can partition into the membrane to cause solubilization of membrane lipids in surfactant micelles.
Xia
W J
WJ
College of Pharmacy, University of Illinois at Chicago, 60612, USA.
Onyuksel
H
H
D005452:Fluoresceins / Q000737:chemistry; D007408:Intestinal Absorption; D008567:Membranes, Artificial; D010539:Permeability; D010743:Phospholipids; D011312:Pressure; D013500:Surface Tension; D013501:Surface-Active Agents / Q000737:chemistry*
D005452:Fluoresceins; D008567:Membranes, Artificial; D010743:Phospholipids; D013501:Surface-Active Agents; C024098:6-carboxyfluorescein