Particulate drug delivery via hair follicles represents a promising concept, although requirements are high. This process must be realized at the desired depth and at the appropriate time, due to the fact that the particles themselves are not able to overcome the follicular skin barrier.In the present study, a novel triggering concept for the release of a model drug from the delivering particles is presented basing on the application of two different particle types of the same size, where one particle type is the drug carrier, and the second one is loaded with a protease. The latter one is supposed to interact with the drugcarrying particles to trigger the drug release. A mixture of both particles was applied on porcine skin samples, followed by follicular analysis. As controls, the particles were applied unaided without protease, and one skin area remained untreated. The investigations revealed that the protease was able to release the model drug from the delivering particles in significant depths within the hair follicle (866 ± 62 nm).Additionally, an uptake of the model drug in the sebaceous gland was observed after release providing a promising novel approach for the development of treatment strategies of different skin diseases.

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