Development of model systems to investigate transdermal transport by advanced optical microscopy

Abstract

Several applications, ranging from standard cosmetic to advanced drug delivery, involve the interaction of different formulations, generally creams or lotions based on emulsions, with biological systems, for example skin. Drug release through the skin, usually referred to as Transdermal Drug Delivery (TDD), requires penetration through the skin barrier, which is a highly organized system composed of several layers with different properties and morphology. TDD can be considered as good alternative to traditional oral or parenteral delivery, which are more painful for the patients. However, standard methods for transdermal studies, such as microscopy, spectroscopy and the well-established Franz cell diffusion chamber, can only capture few aspects of the drug penetration process and do not allow a complete view of the interactions between single components. For the same reasons, although many works have been aimed at improving drug transport by optimization of the carriers (vesicles, nanoparticles, and emulsion droplets), a full understanding of possible enhancer effects is currently lacking. Dimensions, shape or amount of the ingredients in the formulation are considered possible parameters involved in this improvement. Here, an innovative methodology to investigate penetration of different compounds through the skin, by time-lapse confocal microscopy and images analysis is presented. In particular, diffusion of fluorescent molecules in solutions or emulsions is investigated and the corresponding diffusion coefficients are estimated. Based on the formulations properties and their affinity with the medium in which they diffuse, a different behavior is observed. In particular, emulsion microstructure seems to play an important role, enhancing the penetration compared to pure solutions. In addition, the possibility to use soft materials, such as Bicontinuous Emulsion Gels (BEGs), tunable as desired to mimic skin morphology and/or properties are presented as a valid alternative to skin biopsies in penetration studies. The easy preparation and low cost of these materials are some of the main advantages of the proposed approach. To this aim, gelatin is used to mimic hydrophilic properties of skin cells, while cross-linked oil is used for the lipid matrix. A complete characterization of the gelatin gel and its structure-related mechanisms are investigated by Confocal Laser Scanning Microscopy (CLSM), Nuclear Magnetic Resonance (NMR) and birefringence imaging.