Thermosensitive organogels as strategies for the treatment of inflammatory processes: from supramolecular structure to pharmacological evaluation

Abstract

The drug administration on skin offers numerous advantages compared to traditional pathways such as local drug release, easy application and patient compliance, avoiding first-pass biotransformation. However, the stratum corneum complex structural organization is one of the main limitations to drug absorption. On the other hand, morphofunctional changes on stratum corneum are responsible for triggering the synthesis and release of inflammatory cytokines, highlighting the clinical profile of one of the most incident chronic inflammatory dermatoses, Atopic Dermatitis (AD), subject of this proposal. Considering the skin alterations, it is emphasized the need for evaluating the effectiveness of two phytochemicals, such as sulforaphane (SFN) and curcumin (CUR), as well as to develop new carriers systems making them available as possible new therapeutic strategies for the treatment of AD. The technological approach of this proposal refers to the development of different formulations based on lipid-poloxamer organogels, nanostructured colloidal systems that present an oil phase dispersed in an aqueous phase, as tools for the application of phytochemicals to the skin. The different compositions proposed as oil phase were designed to allow the incorporation of high concentrations of hydrophobic molecules (as CUR), as well as to modulate the permeation rate of amphiphilic molecules (such as SFN). One of the differential factors of the proposal is the use of aqueous phase constituted by binary systems with poloxamers (PL) that present different values of hydrophilic-lipophilic balances, being possible to investigate their supramolecular organization by high resolution physicochemical techniques (such as SANS, for example). In addition, the organogels high adhesion capacity to the skin, forming an uniform film, increases the formulation contact time with the application site. Taken together, the factors presented here underscore the need for investigations into the physicochemical characterization of organogels and their interactions with the lipid matrix components of the stratum corneum, enabling the study of the relationship between drug permeation mechanisms and possible structural changes observed in the stratum corneum. In addition to physicochemical assays, the evaluation of biocompatibility, molecular mechanisms and pharmacological effects in vitro and in vivo models, which mimic skin changes in the presence of Atopic Dermatitis, underscores the potential for pharmacotherapeutic and technological innovation of this proposal. (AU)