4.7 Article

Interactions of amphiphilic polyoxazolines formulated or not in lipid nanocapsules with biological systems: Evaluation from membrane models up to in vivo mice epidermis

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DOI: 10.1016/j.ejpb.2022.10.009

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Skin penetration; Lipid membrane insertion; POxylated emulsifiers; Nanoformulations; Topical delivery

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In this study, the potential of amphiphilic polyoxazolines (POx) to interact with biological membranes was evaluated. The study found that POx has excellent penetration into lipid bilayers and cells, and its interactions with membranes depend on the nature of the alkyl chain constituting the POx. Both saturated and unsaturated POx types were efficiently accumulated in the stratum corneum barrier of mouse skin, showing potential for topical delivery of active molecules.
In this study, we evaluated the potential of amphiphilic polyoxazolines (POx) to interact with biological mem-branes thanks to models of increasing complexity, from a simple lipid bilayer using giant unilamellar vesicles (GUV), to plasma membranes of three different cell types, fibroblasts, keratinocytes and melanocytes, which are found in human skin. Upon assessing an excellent penetration into GUV membranes and cultured cells, we addressed POx's potential to penetrate the murine skin within an in vivo model. Exposure studies were made with native POx and with POx encapsulated within lipid nanocapsules (LNC). Our findings indicate that POx's in-teractions with membranes tightly depend on the nature of the alkyl chain constituting the POx. Saturated C16POx insert rapidly and efficiently into GUV and plasma membranes, while unsaturated C18:2POx insert to a smaller extent. The high amount of membrane-inserted saturated C16POx impacts cell viability to a greater extent than the unsaturated C18:2POx. The in vivo study, performed on mice, showed an efficient accumulation of both POx types in the stratum corneum barrier, reaching the upper epidermis, independently of POx's degree of saturation. Furthermore, the formulation of POx into lipid nanocapsules allowed delivering an encapsulated molecule, the quercetin, in the upper epidermis layers of murine skin, proving POx's efficacy for topical delivery of active molecules. Overall, POx proved to be an excellent choice for topical delivery, which might in turn offer new possibilities for skin treatments in diseases such as psoriasis or melanomas.

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