Hyaluronic acid-based nanoemulsions for vitamin E encapsulation - Experimental and molecular dynamics studies

Oil-in-water (O/W) emulsions are widely applied in pharmaceutical and cosmetic formulations due to their ability to solubilize and deliver hydrophobic compounds to specific sites. Herein, we report the preparation and physicochemical characterization of nanoemulsions (NEs) with an oil phase composed of glyceryl trioctanoate (GTO) and vitamin E (Vit-E, a model hydrophobic bioactive compound), stabilized by amphiphilic derivatives of hyaluronic acid (AmHAs). HA was modified by covalent attachment of hexadecyl or octadecyl substituents, enabling efficient interfacial self-assembly during ultrasonication-assisted emulsification. Cryogenic transmission electron microscopy revealed the formation of spherical GTO/Vit-E nanodroplets with diameters of 30-250 nm. Additionally, an effect of the oil core composition on NE stability was observed, arising from heterogeneity within the oil phase. The highest stability was achieved at a GTO:Vit-E ratio of 1:1, highlighting the system's capacity for high Vit-E loading. The stabilization mechanism arises from the penetration of hydrophobic alkyl groups into the oil phase, while the hydrophilic polysaccharide backbone remains in the aqueous phase, forming a steric barrier that prevents droplet aggregation and coalescence. Molecular dynamics (MD) simulations revealed preferential localization of GTO at the oil-water interface and a heterogeneous distribution of Vit-E within the core. This organization promotes hydrogen bonding and water-mediated interactions between HA and GTO. The structural stability, biocompatibility of the HA shell, and high loading efficiency make these nanoemulsions promising carriers for delivery of poorly water-soluble bioactives.