Ascorbyl palmitate interaction with phospholipid monolayers: Electrostatic and rheological preponderancy

Ascorbyl palmitate (ASC(16)) is an anionic amphiphilic molecule of pharmkological interest due to its antioxidant properties. We found that ASC(16) strongly interacted with model membranes. ASC(16) penetrated phospholipid monolayers, with a cutoff near the theoretical surface pressure limit. The presence of a lipid film at the interface favored ASC(16) insertion compared with a bare air/water surface. The adsorption and penetration time curves showed a biphasic behavior: the first rapid peak evidenced a fast adsorption of charged ASC(16) molecules to the interface that promoted a lowering of surface pH, thus partially neutralizing and compacting the film. The second rise represented an approach to the equilibrium between the ASC(16) molecules in the subphase and the surface monolayer, whose kinetics depended on the ionization state of the film. Based on the Langmuir dimiristoylphosphatidylcholine + ASC(16) monolayer data, we estimated an ASC(16) partition coefficient to dimiristoylphosphatidylcholine monolayers of 1.5 x 10(5) and a Delta G(p) = -6.7 kcal.mol(-1). The rheological properties of the host membrane were determinant for ASC(16) penetration kinetics: a fluid membrane, as provided by cholesterol, disrupted the liquid-condensed ASC(16)-enriched domains and favored ASC(16) penetration. Subphase pH conditions affected ASC(16) aggregation in bulk: the smaller structures at acidic pHs showed a faster equilibrium with the surface film than large lamellar ones. Our results revealed that the ASC(16) interaction with model membranes has a highly complex regulation. The polymorphism in the ASC(16) bulk aggregation added complexity to the equilibrium between the surface and subphase form of ASC(16), whose understanding may shed light on the pharmacological function of this drug. (C) 2013 Elsevier B.V. All rights reserved.