Ascorbyl palmitate interaction with phospholipid monolayers: Electrostatic and rheological preponderancy

Abstract

Ascorbyl palmitate (ASC16) is an anionic amphiphilic molecule of pharmacological interest due to its antioxidant properties. We found that ASC16 strongly interacted with model membranes. ASC16 penetrated phospholipid monolayers, with a cutoff near the theoretical surface pressure limit. The presence of a lipid film at the interface favored ASC16 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 ASC16 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 ASC16 molecules in the subphase and the surface monolayer, whose kinetics depended on the ionization state of the film. Based on the Langmuir dimiristoylphosphatidylcholine+ASC16 monolayer data, we estimated an ASC16 partition coefficient to dimiristoylphosphatidylcholine monolayers of 1.5×10(5) and a ΔGp=-6.7kcal·mol(-1). The rheological properties of the host membrane were determinant for ASC16 penetration kinetics: a fluid membrane, as provided by cholesterol, disrupted the liquid-condensed ASC16-enriched domains and favored ASC16 penetration. Subphase pH conditions affected ASC16 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 ASC16 interaction with model membranes has a highly complex regulation. The polymorphism in the ASC16 bulk aggregation added complexity to the equilibrium between the surface and subphase form of ASC16, whose understanding may shed light on the pharmacological function of this drug.

Lipid Monolayers at the Air–Water Interface

“…In other words, as the bulk pH increases beyond the surfactant pK a , the surface pH does not change in the same fashion, since the electrical double layer acts as a buffer, resulting in a more acid interface and a less charged monolayer than that expected in the absence of the cloud of contraions. Hence, this effect is less marked when the ionic strength of the subphase is high, since the surface charge is screened at closer distances and by other ions that are different from H + [57,61], thus suggesting that salt concentration is another parameter regulating the mixing-demixing regions of the phase diagrams of mixtures with an ionizing component.…”

“…Langmuir films have also been widely used to study the interaction and penetration of soluble molecules (anesthetics [48], proteins and peptides [49][50][51][52][53][54][55][56], vitamins [57], etc.) in membranes.…”

The amphiphilic alkyl ester derivatives of l -ascorbic acid induce reorganization of phospholipid vesicles

“…We also explored the occurrence of condensed drug-enriched domains laterally segregated from the phospholipid rich phase, as has been shown to occur in analogues monolayer systems [10,11]. …”

“…We recently studied the surface behavior of ASCn with acyl chains of different lengths, showing that these type of drugs have high surface activity where they are able to form stable Gibbs monolayers and were also capable to penetrate into tightly-packed phospholipid monolayers [10]. Subtle chemical differences in these compounds (which contain acyl chains of C16, C14 and C12) have large implications on the surface activity and upon the in-plane organization of the ASCn films as well as in their ability to be integrated into lipid monolayers [10][11][12][13]. We also demonstrated that these differences induce differential changes of the physicochemical properties of the targeted lipid membrane and regulate the extent of drug incorporation and the kinetics of the penetration process [12].…”

Lipid-packing perturbation of model membranes by pH-responsive antimicrobial peptides

“…In the phase coexistence region, solid domains are formed and grow during the compression of the lipid film (Heckl et al 1986;Miller and Mohwald 1987;Vanderlick and Möhwald 1990). The separate phases and the morphology of these solid domains can be visualized by FM (Lösche et al 1983;Weis and McConnell 1984;Mohwald 1990) or Brewster angle microscopy (BAM) (Hoenig and Moebius 1991;McConlogue and Vanderlick 1997;Mottola et al 2013) during film compression or by atomic force microcopy (Clausell et al 2004;Mularski et al 2015) in films transferred to a solid substrate at a given surface pressure (Mangiarotti and Wilke 2015). The pressure at which the phase coexistence takes place and the extension of the plateau are very sensitive to the pH, ionic conditions and temperature of the subphase (Mohwald 1990;Maltseva et al 2006;Vega Mercado et al 2011).…”