The development of topical pharmaceutical products for dermatological indications remains challenging due to the often problematic physicochemical properties of drugs and the lack of appropriate methods to evaluate their skin delivery efficacy. The aim of this thesis was to explore ways to address these challenges – first, by the evaluation of polymeric micelle formulations to enhance the cutaneous bioavailability of immunosuppressant drugs and second, by the development of quantitative and qualitative techniques to investigate the cutaneous spatial biodistribution of xenobiotics. The design of polymeric micelles has proven to be a promising alternative to meet the unsatisfied needs of patients suffering from autoimmune skin diseases. In addition, the determining factors influencing the formulation of polymeric micelles and drug bioavailability have been successfully highlighted. Moreover, two qualitative and quantitative approaches, respectively the cutaneous biodistribution method and DESI-MS imaging technique, have demonstrated a strong complementarity to deepen knowledge on skin transport and drug penetration pathways.