Hyaluronic Acid-Modified Nanoemulsions Enable Targeted Transdermal Delivery of Hydroxypinacolone Retinoate

Hyaluronic acid (HA) has been extensively utilized in cosmetic products and topical formulations due to its remarkable moisturizing properties and the potential to enhance transdermal drug delivery. In this study, phytosphingosine (PS) was utilized as a positive charge inducer in the preparation of positively charged nanoemulsions (PS-HPR-NE). Subsequently, hydroxypinacolone retinoate (HPR) was modified onto the surface of 8 kDa HA nanoemulsions via electrostatic adsorption technology, yielding the HA-HPR-NE composite system. The resulting nanoemulsion exhibited a particle size of 116.00 ± 2.34 nm, a polydispersity index (PDI) of 0.100 ± 0.011, and a surface potential of -17.42 ± 0.19 mV. The findings of the storage stability and stability analyzer assessments demonstrated excellent stability. Subsequent analysis of cell uptake experiments revealed significantly higher fluorescent labeling both inside and outside cells in the HA-HPR-NE group compared to that in the PS-HPR-NE group. In vivo skin penetration fluorescence results indicated that HA-HPR-NE exhibited a higher fluorescence intensity in deep skin layers than PS-HPR-NE and free HPR. In vitro diffusion cell tests demonstrated that PS-HPR-NE exhibited higher skin retention rates and cumulative penetration rates than the control group, thus confirming its highly efficient drug release effect. In addition, the red blood cell hemolysis assay and human patch test demonstrated that this nanoemulsion significantly reduced the HPR irritation. In comparison with conventional cationic nanoemulsions, HA-targeted nanoemulsions demonstrate enhanced potential and a wider range of potential applications in the domains of transdermal drug-delivery and targeted drug-delivery systems.