Membrane Perturbation by Surfactant Candidates for STD Prevention

We studied surfactant-induced leakage of vesicles, comparing the efficacy of four surfactants with current or potential application in contraception and the prevention of sexually transmitted diseases: nonoxynol-9 (N-9); the amphoteric mixture known as C31G; benzalkonium chloride (BZK); sodium dodecyl sulfate (SDS). Several features are generic to the membrane leakage process independent of the surfactant used. The kinetics of the leakage process is well-characterized by a single exponential rate of release, and the rate constant increases with surfactant concentration according to a power-law dependence. Notably, however, the formation of surfactant micelles serves to enhance the rate of vesicle leakage. A method for quickly changing the effective surfactant concentration in situ, and thus the rate of vesicle leakage, is presented. Specifically, methyl-β-cyclodextrin is added to the external aqueous solution and forms inclusion complexes with surfactant, effectively reducing the concentration of soluble surfactant. These studies show that the partitioning of surfactant between the aqueous solution and the lipid membrane is quick and certainly not a rate-limiting step in the membrane leakage process. We also show that the distribution of surfactant between the membrane and solution does not strictly follow a simple partitioning model. In comparing the membrane perturbing capabilities of the four surfactants, we find that C31G > BZK > N-9 ≫ SDS. Finally, our studies clearly show that the potencies of the surfactants toward membrane attack do not scale with the magnitudes of their critical micelle concentrations.