Design and characterisation of a film-forming emulsion combining enhanced skin permeability with prolonged drug...

Water-in-oil nanoemulsions can improve the skin permeation of encapsulated hydrophilic drugs; however, their limited residence on the skin restricts prolonged drug delivery. To address this limitation, we developed a novel film-forming emulsion (FFE) by incorporating our previously developed water-in-oil nanoemulsion (W_G/O-NE) into an in situ film-forming matrix, thereby combining the penetration-enhancing function of W_G/O-NE with prolonged skin residence. W_G/O-NE with a mean particle size of 141.2 ± 0.6 nm was incorporated into the matrix to produce FFE droplets with a mean diameter of 1.02 ± 0.47 μm. Formulation optimisation identified 10% (w/v) PVA and 10% (v/v) glycerol as balancing skin permeability and adhesion. FFE formed a flexible, adherent film. Confocal laser scanning and scanning electron microscopy revealed interconnected porous structures, and W_G/O-NE released from the dried film retained a nanoscale particle size distribution. In an in vivo mouse skin penetration study, FFE increased skin retention of fluorescein, a hydrophilic model drug, by 2.31- and 3.99-fold compared with the film-forming system and W_G/O-NE, respectively, and enabled delivery to subcutaneous tissue at depths of ≥375 μm. Fluorescein remained detectable for up to 48 h under repeated application. Safety evaluation revealed no obvious tissue damage, and transient epidermal thickening resolved within 2 days after film removal. These findings suggest that W_G/O-NE can be released from the FFE film and that FFE may combine film-mediated skin retention with the release and penetration-enhancing functions of W_G/O-NE. Thus, FFE may serve as a platform for prolonged skin residence and deep delivery of hydrophilic drugs.