Enhancing Skin Penetration of a Hydrophilic, Large Molecular Weight Compound Using a Nanoparticle-in-Oil Dispersion

The hyaluronic acid levels in the body decline over time due to various factors, such as aging and UV irradiation. Therefore, technologies that can directly deliver hyaluronic acid across the skin are clinically relevant. In this study, we fabricated a nanoparticle-in-oil dispersion (NOD) by dehydrating a water-in-oil emulsion containing rhodamine B isothiocyanate-labeled sodium hyaluronate (RHA; average molecular weight, 1200000-1600000). To clarify the effect of NOD on the transdermal absorption of RHA, in vitro experiments were performed using three formulations: RHA-loaded NOD (RHA-NOD), an olive oil dispersion of RHA (RHA-O) containing a surfactant (polyglyceryl-6 polyricinoleate), and an olive oil dispersion of RHA (oil dispersion). The RHA concentrations in the RHA-NOD, RHA-O, and oil dispersion, each prepared at 0.03% (w/v), were 144.5 ± 9.1, 2.5 ± 0.3, and 4.0 × 10^-2 ± 0.3 × 10^-2 µg/mL, respectively. Dynamic light-scattering and field emission scanning electron microscopy revealed a uniform size of 150 nm for the NOD. The skin penetration flux of the RHA-NOD was 3.4 times that of RHA-O. Analysis of cryosections indicated that NOD significantly increased the RHA concentration from the skin surface to a depth of 140 µm. These findings position NODs as platforms with the potential to maintain a high concentration of RHA on the skin surface.