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

Abstract

The use of penetration enhancers (chemical or physical) has been proven to dramatically improve the penetration of therapeutics. Nevertheless, their use poses great risks, as they can lead to permanent damage of the skin, reduce its barrier efficiency, and result in the intrusion of harmful substances. Among the most used skin penetration enhancers, water is greatly accepted because skin quickly recovers from its exposure. Nanocapsules (NCs) represent a promising combination of the 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, NCs were synthesized with a void core of 100 nm in diameter, a thermoresponsive shell based on different ratios of poly(N-isopropylacrylamide) and poly(N-isopropylmethacrylamide) as thermoresponsive polymers, and dendritic polyglycerol as a 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 thermoresponsive 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 increase the amount of deuterated water that penetrated into the viable epidermis. 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.

Nanocarriers for Skin Applications: Where Do We Stand?

“…Moreover,i tw as demonstrated that this effect could be further increased upon application of athermal trigger,asobserved in the fluorescence intensity in Figure 5E and SRS in Figure 5F.F inally,skin hydration caused by tNCs was sufficient to significantly enhance the skin penetration of Atto Oxa12 NHS ester,ahigh-molecular-weight dye,a s amodel drug. [50] In addition to inducing skin hydration, thermoresponsive nanocarriers have many attractive features for dermal drug delivery.D ue to the natural temperature gradient across the skin and the possibility to control the thermal response, thermoresponsive nanocarriers have been investigated extensively in dermal drug delivery applications. [51] Thestructure of thermoresponsive nanocarriers undergoes physiochemical changes with environmental temperature variation at as pecific range,k nown as the critical solution temperature.…”

Nanocarriers for Skin Applications: Where Do We Stand?

“…Finally, skin hydration caused by tNCs was sufficient to significantly enhance the skin penetration of Atto Oxa12 NHS ester, a high‐molecular‐weight dye, as a model drug. [50] …”

Multifunctional Polymeric Nanogels for Biomedical Applications

“…After being triggered by heat, this nanocarrier demonstrated improved skin penetration because it could move through the stratum corneum to the viable epidermis. Interestingly, the nanocapsule exhibited the penetration of a high molecular weight Atto oxa12 (MW = 835 g/mol) into the viable epidermis, which indicated increased skin penetration compared with DMSO, which was used as the positive control [ 41 ].…”