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Quantitative Analysis of Ligands Effects on Bioefficacy of Nanoemulsion encapsulating Depigmenting Active

Atrux-Tallau, N., Lasselin, J., Han, S. H., Delmas, T., & Bibette, J. Colloids and Surfaces B: Biointerfaces122 (2014): 390-395.

Efficient skin delivery of active molecules is the main challenge to overcome in order to achieve significant therapeutic efficiency of cosmetics or dermo-pharmaceutical products. Nanocarriers such as nanoemulsions have been envisaged to overcome main challenges of active solubilization, protection and transport to their site of biological action. Nonetheless, their skin permeation is still limited and a new approach is required to significantly improve bioavailability. We here explored the possibility of increasing the whitening activity of a model active, licorice, by implementing a targeting approach of nanoemulsions to melanocyte cells. Targeting requires particle surface modification with specific molecules favoring nanoemulsion/cells contact through ligand-receptor interactions. The uniqueness of our strategy is that unlike classical covalent chemical grafting, we propose a self-assembled strategy based on a selection of amphiphilic ligands able to localize at nanoemulsion droplets interface. Four ligand candidates were thus assayed in terms of formulation and in vitro biological evaluation: a palmitoyl-peptide (palmitoyl-GQPR), a lipidized hyaluronic acid (caproyl-HA) and two amphiphilic actives (polydatin and isopilosine). A functional analysis based on a cellular assay of melanin inhibition was realized. The intrinsic properties of ligand candidates were first evaluated. Then, nanoemulsions encapsulating a drug model, licorice, and targeted with the different ligand candidates were assayed. The use of caproyl-HA significantly improved bioefficacy of the encapsulated licorice, suggesting a better interaction with the cells. The improved value observed was not attributed to a synergetic action as caproyl-HA did not evidence intrinsic melanogenesis modulation activity. In this study, we demonstrated the feasibility of targeting nanoemulsion droplets without chemical covalent modification of nanoemulsion droplets to increase bioefficacy of encapsulated drugs in vitro.

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