Ionic Liquid-Enabled Topical Delivery of Immunomodulators

Skin is one of the most immunologically active organs of the body due to the presence of diverse immune cells and its active involvement in the innate and adaptive immunity. Because of its unique location and immunological role, skin offers an excellent site for the introduction of immunomodulators to synergize with the active immune microenviroment for the desired outcome. However, delivery of immunomodulators to the skin remains a significant challenge due to the skin's barrier properties. Here, we report an ionic liquid (IL)-based strategy to formulate and deliver immunomodulators to the skin. Using imiquimod (IMQ) and triamcinolone acetonide (TCA) as the respective model immunoactive and immunosuppressive drugs, we demonstrated that ILs significantly enhanced the solubility of immunomodulators. In addition, ILs enabled the formulation of the immunomodulators into stable, topically applicable forms. Our ex vivo skin penetration studies revealed that the IL formulations outperformed respective commercial topical comparators and delivered significantly more immunomodulators to deep skin layers. The lead IMQ formulation exhibited >10-fold better efficacy in delivering IMQ to the deep skin layers as compared to the commercial 5% IMQ cream. Lead TCA formulations achieved a dose level in deep skin layers that is comparable to that by clinically used intralesional injections. Our data collectively suggest that the IL-based strategy can be a simple and effective platform for delivery of immunomodulators to the skin.