Ex vivo UV-vis and FTIR photoacoustic spectroscopy of natural nanoemulsions from cellulose nanocrystals and saponins topically applied into the skin: Diffusion rates and physicochemical evaluation.

Nanoemulsions are increasingly gaining importance in the development of topically applied medicine and cosmetic products because their small droplets favor the penetration rates of active compounds into the body. In this scenario, the measurements of their diffusion rates as well as eventual physicochemical changes in the target tissues are of utmost importance. It is also recognized that the use of natural surfactants can avoid allergic reactions as frequently observed for synthetic products. The natural saponins extracted from Sapindus Saponaria have the property of forming foam and are exploited as biocompatible and biodegradable, while cellulose nanocrystals are known to increase the stability of a formulation avoiding the coalescence of drops at the interface. Therefore, nanoemulsions combining natural saponins and cellulose nanocrystals are promising systems that may facilitate greater diffusion rates of molecules into the skin, being candidates to substitute synthetic formulations. This study applied the Photoacoustic Spectroscopy technique to measure the diffusion rates and the physicochemical properties of nanoemulsified formulations containing saponins and cellulose nanocrystals topically applied to the skin. The ex vivo study combined the first-time photoacoustic measurements performed in both ultraviolet-visible and mid-infrared spectral regions. The toxicity of these formulations in L929 cells was also evaluated. The results showed that the formulations were able to propagate throughout the skin to a depth of approximately 756 µm, reaching the dermal side. The non-observation of absorbing band shifting or new bands in the FTIR spectra suggests that there were no structural changes in the skin as well as in the formulations after the nanoemulsions administration. The cytotoxicity results showed that the increase of cellulose nanocrystals concentration decreased cellular toxicity. In conclusion, the results demonstrated the advantage of combining photoacoustic methods in the ultraviolet-visible and mid-infrared spectral regions to analyze drug diffusion and interaction with the skin tissues. Both methods complement each other, allowing the confirmation of the nanoemulsion diffusion through the skin and also suggesting there were no detectable physicochemical changes in the tissues. Formulations stabilized with saponins and cellulose nanocrystals showed great potential for the development of topically administered cosmetics and drugs.