Prediction of the penetration depth of multi-lamellar liposomes in artificial skin. Application to the vectorization of corticosteroid in human skin

Antoine Bernasqué; Muriel Cario; Stéphanie Krisa; Sophie Lecomte; Chrystel Faure

doi:10.1016/j.ejpb.2023.09.007

Prediction of the penetration depth of multi-lamellar liposomes in artificial skin. Application to the vectorization of corticosteroid in human skin

Eur J Pharm Biopharm. 2023 Oct:191:303-314. doi: 10.1016/j.ejpb.2023.09.007. Epub 2023 Sep 13.

Authors

Antoine Bernasqué¹, Muriel Cario², Stéphanie Krisa³, Sophie Lecomte⁴, Chrystel Faure⁵

Affiliations

¹ CBMN, Université de Bordeaux, CNRS, Bordeaux INP, UMR 5248, F-33600 Pessac, France; U1312-BRIC, Inserm, Université de Bordeaux, National Reference Center for Rare Skin Diseases, Bordeaux, France.
² U1312-BRIC, Inserm, Université de Bordeaux, National Reference Center for Rare Skin Diseases, Bordeaux, France.
³ INRAE, Bordeaux INP, UR œnologie, EA 4577, USC 1366, ISVV, Université de Bordeaux, 33140 Villenave d'Ornon, France.
⁴ CBMN, Université de Bordeaux, CNRS, Bordeaux INP, UMR 5248, F-33600 Pessac, France.
⁵ CBMN, Université de Bordeaux, CNRS, Bordeaux INP, UMR 5248, F-33600 Pessac, France. Electronic address: chrystel.faure@enscbp.fr.

PMID: 37708944
DOI: 10.1016/j.ejpb.2023.09.007

Abstract

Our previous work showed that the size, elasticity and charge of multi-lamellar liposomes (MLLs) could not be considered separately to predict the fate of MLLs in the skin [1]. Based on this study, we developed several MLLs formulations containing a corticosteroid, betamethasone 17-valerate (B17) to transport the drug into the stratum corneum, living epidermis, dermis or through the skin. MLLs encapsulation efficiency was found to exceed 74 ± 3 % in all cases. In addition, we showed that MLLs protected the corticosteroid from thermal degradation. Comparing the penetration depth of all MLLs within artificial skin measured by Raman imaging, we established an equation for its determination, given the MLLs elasticity and size. This equation was verified experimentally on human explants: quantification of B17 in each skin layer, as well as its transdermal passage by ultra-high performance liquid chromatography, confirmed that B17 was predominantly and significantly transported in the desired layer. Eventually, we showed the benefits in using B17-loaded MLLs instead of a B17-containing pharmaceutical cream in terms of B17 penetration and thermal degradation.

Keywords: Betamethasone-17-valerate skin distribution; Multi-lamellar liposomes; Raman imaging; Skin penetration prediction; Thermal protection.