Innovative delivery systems for the local administration of immunomodulatory drugs

Abstract

Immunomodulatory drugs are important tools for the treatment of numerous local diseases. Their topical administration can be particularly useful to obtain a therapeutic effect at the site of interest, limiting at the same time the systemic side effects. Despite this great potential, the local administration is challenging for several reasons and, in particular, for the presence of biological barriers limiting drug penetration and accumulation in the target tissue. The aim of this work was the development of innovative formulations for the local administration of drugs with immunomodulatory properties. Particular attention has been addressed to novel technologies, such as microemulsions and nanoparticles, which could be useful to optimize the administration, increasing the local delivery and/or reducing systemic absorption. After a general introduction on the immune system, the drugs used and the local administration, the work was developed in two different parts. In PART 1 the dermal administration of an immunostimulant drug, imiquimod, was studied. Initial studies were performed in order to highlight the mechanisms involved in the skin accumulation, then attention was directed to the development of innovative formulations based on microemulsion technology to increase the efficiency of skin delivery. In PART 2 two immunosuppressive drugs (corticosteroids) were selected: triamcinolone acetonide (TA) and dexamethasone palmitate (DXP). In case of TA, microemulsions for the buccal delivery were developed, characterized and evaluated in vitro. For DXP, nanoparticles based on hyaluronic acid conjugate for the topical drug delivery were prepared.