Polyglycerol-Based Thermoresponsive Nanocapsules Induce Skin Hydration and Serve as a Skin Penetration Enhancer

The use of penetration enhancers (chemical or physical) has been proven to dramatically improve the penetration of therapeu-tics. Nevertheless, their use poses great risks, as they can lead to permanent damage on the skin, reducing its barrier efficien-cy and resulting in the intrusion of harmful substances. Among the most used skin penetration enhancers, water is greatly accepted since skin quickly recovers from its exposure. Nanocapsules (NCs) represent a promising combination of carrier system and penetration enhancer because their water containing void combined with their polymer-based shell can be used to induce high local skin hydration, while simultaneously aiding the transport of drugs across the skin barrier. In this study, nanocapsules were synthesized with a void core of 100 nm in diameter, a thermoresponsive shell based on different ratios of poly(N-isopropylacrylamide) (PNIPAM) and poly(N-isopropylmethacrylamide) (PNIPMAM) as thermoresponsive polymers, and dendritic polyglycerol (dPG) as macromolecular cross-linker. These NCs can shrink or swell upon a thermal trigger, which was used to induce the release of the entrapped water in a controlled fashion. The interactions and effects of ther-moresponsive NCs on the stratum corneum of excised human skin were investigated using fluorescence microscopy, high resolution optical microscopy, and stimulated Raman spectromicroscopy. It could be observed that the thermoresponsive NCs could increase the amount of deuterated water that penetrated in the viable epidermis (VE). Moreover, NCs increased the skin penetration of a high molecular weight dye (Atto Oxa12 NHS ester, MW = 835 g/mol) with respect to formulations in water or 30% DMSO, emphasizing the features of the NCs as a skin penetration enhancer.