The Role of Internal and External Stimuli in the Rational Design of Skin-specific Drug Delivery Systems.

The concept of skin-specific drug delivery with a spatio-temporal control has just recently received concerns in dermatology. Inspired by the progress in smart materials and their perspective application in medicine science, development of stimuli responsive drug delivery systems with skin-specificity has become possible, which has led to a new era in the localized treatment of skin diseases. This review highlights both the internal and external stimuli that have been employed in this field, with a focus on their implication on the rational design of pharmaceutical formulations, especially those nanoscale drug carriers that are able to provide release of payloads with a precise spatio-temporal control in response to specific stimuli. Also, the strategy of dual stimuli responsive drug delivery systems will be discussed for further improvement of the efficacy of skin drug delivery. The prominent examples of the established approaches are described as comprehensive and current as possible. The review is expected to provide some inspiration for utilizing different stimuli for realizing the site-specific and on-demand drug delivery to the skin.