The rheological properties of lipid monolayers modulates the incorporation of L-ascorbic acid alkyl esters

Y. ZULUETA DIAZ; M. MOTTOLA; R. VICO; N. WILKE; M.L. FANANI

LANGMUIR

AMER CHEMICAL SOC

Lugar: Washington; Año: 2016 vol. 32 p. 587 - 595

0743-7463

In this work, we tested the hypothesis that the incorporation of amphiphilic drugs into lipid membranes may beregulated by their rheological properties. For this purpose, two members of the L-ascorbic acid alkyl esters family (ASCn) wereselected, ASC16 and ASC14, which have different rheological properties when organized at the air/water interface. They arelipophilic forms of vitamin C used in topical pharmacological preparations. The effect of the phase state of the host lipidmembranes on ASCn incorporation was explored using Langmuir monolayers. Films of pure lipids with known phase states havebeen selected, showing liquid-expanded, liquid-condensed, and solid phases as well as pure cholesterol films in liquid-orderedstate. We also tested ternary and quaternary mixed films that mimic the properties of cholesterol containing membranes and ofthe stratum corneum. The compressibility and shear properties of those monolayers were assessed in order to define its phasecharacter. We found that the length of the acyl chain of the ASCn compounds induces differential changes in the rheologicalproperties of the host membrane and subtly regulates the kinetics and extent of the penetration process. The capacity for ASCnuptake was found to depend on the phase state of the host film. The increase in surface pressure resultant after amphiphileincorporation appears to be a function of the capacity of the host membrane to incorporate such amphiphile as well as therheological response of the film. Hence, monolayers that show a solid phase state responded with a larger surface pressureincrease to the incorporation of a comparable amount of amphiphile than liquid-expanded ones. The cholesterol-containing films,including the mixture that mimics stratum corneum, allowed a very scarce ASCn uptake independently of the membranediffusional properties. This suggests an important contribution of Cho on the maintenance of the barrier function of stratumcorneum.