Influence of Molecular Structure and Physicochemical Properties of Immunosuppressive Drugs on Micelle Formulation Characteristics and Cutaneous Delivery

This study investigates how subtle differences in the molecular properties of three immunosuppressive drugs, namely, sirolimus, pimecrolimus, and tacrolimus, affect their behavior in polymeric micelles and their cutaneous delivery. Using TPGS-based micelles, we characterized size, drug loading, stability, release kinetics, and biodistribution in skin layers. While all three drugs formed stable micelles with high incorporation efficiencies, clear differences emerged in release profiles and skin penetration, driven largely by their aqueous solubility and lipophilicity. The findings highlight that even structurally similar molecules can behave differently in micellar systems and on the skin, emphasizing the need to optimize micelle formulations based on drug-specific properties.