title: The effect of non-deuterated and deuterated isopropyl myristate on the thermodynamical and structural behavior of a 2D Stratum Corneum model with Ceramide [AP].
abstract: Isopropyl myristate (IPM) is a widely used penetration enhancer in pharmaceutical formulations, however, its mechanism of action on a molecular scale is still not completely understood. Previous work using a quaternary Stratum Corneum (SC) lipid model in bulk suggested the incorporation of isopropyl myristate into the SC lipid matrix, phase separation, and perturbation of the multilamellar lipid assembly. Here, we used 2D Langmuir monolayers of a ternary SC lipid model, containing ceramide AP C18:18, stearic acid and cholesterol in a molar ratio of [1:1:0.7], respectively, to shed light on the mechanism of action of this important lipophilic penetration enhancer. To do so, the synthesis of chain deuterated isopropyl myristate was successfully performed in order to study the different coupling possibilities between the hydrogenated and deuterated IPM and the alkyl chains of the SC molecules. Our results indicate that only a small portion of IPM is able to mix with our SC model leading to a limited fluidizing effect (small increase of the wavenumber of CH2stretching vibration, increase of the SC layer flexibility), but will be squeezed out at higher lateral pressures. Furthermore, the deuteration of IPM enhances the miscibility with this SC model, probably due to a different coupling between the alkyl chains or the alkyl and deuterated chains. Additionally, using the pure D-form of CER[AP] in the SC model amplifies the obtained results.
authors.affiliation: Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany.
authors.forename: J S L
authors.initials: JS
authors.lastname: Oliveira
authors.affiliation: Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Strasse 4, 06120 Halle, Germany; Institute of Medical Physics and Biophysics, University of Leipzig, Härtelstraße 16-18, 04107 Leipzig, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Lange
authors.affiliation: Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Strasse 4, 06120 Halle, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Dobner
authors.affiliation: Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany. Electronic address: brezesinski@mpikg.mpg.de.
authors.forename: G
authors.initials: G
authors.lastname: Brezesinski
mesh_terms: D002518:Ceramides / Q000737:chemistry*; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D009226:Myristates / Q000737:chemistry*; D012867:Skin / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D002518:Ceramides; D008055:Lipids; D009226:Myristates; C008205:isopropyl myristate
keywords: Deuteration; Isopropyl myristate; Langmuir monolayer; Penetration enhancer; Stratum corneum lipids; Transdermal drug delivery