Hydrophobically-modified hyaluronic acid as stabilizer for oil-in-water emulsions to improve epidermis biodistribution of actives.

Encapsulation systems to deliver hydrophobic active ingredients or drugs via topical application on the skin is, still, one of the most commercialized products for cosmetic and dermatology application. Despite the increasing number of delivery systems reported, the most efficient to encapsulate hydrophobic compounds remains oil-in-water (O/W) emulsions, but the surfactant currently used are mostly from petroleum source. Here, we have evaluated the modification of hyaluronic acid (HA), which is a natural polysaccharide that is abundant in biological tissues and has excellent potential for reconstructing synthetic extracellular matrix analogues, with methacrylate groups (HA-MA) as emulsion stabilizer. The presence of the hydrophobic methacrylate groups on the HA conferred interfacial activity to the polysaccharide, enabling the stabilization of oil-in-water emulsions (EMs). The study of the effect of the degree of substitution (DS) of methacrylate groups on the interfacial activity of HA-MA for the production of O/W emulsion showed that stable emulsions were only produced for DS between 50 % and 100 %, as judged by monitoring the droplet size distribution by laser diffraction. Surface tension studies confirmed that this range of DS was required to adsorb at the air-water interface. However, it is important to mention that the observed decrease of surface tension at around 63 mN/m was not as low as one would expect for a surfactant with good interfacial activity. This suggest that HA-MA might not be considered as a highly efficient emulsifier. Despite such characteristic, stable emulsions (>1 month) were obtained at pH 4.2 when relatively highly polar oils, such as Octyl Palmitate and MCT, were used, at concentrations of HA-MA of 10 and 15 wt% (based on the amount of oil emulsified). Regarding the biological evaluation in vitro, HA-MA and HA-MA-stabilized emulsion did not show any cytotoxicity to skin relevant cell lines, such as keratinocytes and fibroblasts. More importantly, the biological activity of HA remained even with the presence of methacrylate group which mean that the beneficial effect of HA as cosmetic active ingredient will be maintained. In addition, irritation test according to ISO 9001:2008 on human reconstructed epidermis showed that the topical application of the emulsion did not affect the skin cell viability and was classified as non-irritant. Finally, confocal laser microscope studies after topical application of HA-MA-stabilized EMs, containing Nile Red in the oil phase, on human reconstructed skin showed that higher biodistribution of the dye in the epidermis (8-fold) compared to the non-encapsulated compounds. These promising results demonstrate that HA-MA-stabilized O/W emulsions could have double effect after topical application on the skin: i) maintain the properties of HA as cosmetic ingredient and ii) as an efficient permeation enhancer of ingredient on the skin. This would potentially increase the bioactivity of drugs and cosmetic ingredients, as well as offering the beneficial effect of HA.