Bioavailability of Hydrogen Sulfide in a topical nanoformulation in experimental psoriasis

Abstract

Pruritus or itching, as pain, is a sensory experience similarly aversive associated with the desire to scratch. However, unlike the pain, there is a great lack of studies that explore the stimuli or mechanisms of action capable of inducing the perception of pruritus/itching. The current therapy for this symptom limited to the class of anti-histamine drugs, which acts not always satisfactory for some forms of chronic pruritus, commonly seen in skin diseases such as dermatitis and psoriasis. Psoriasis is an immunomediated chronic inflammatory disease that affects 2 to 4% of the global population. It is characterized, mainly, by skin lesions associated with intense pruritus, which reduce the life quality of patients. The available therapies (eg. corticoids, biologic agents) for psoriasis are not always effective, as they could induce adverse effects or are expensive. Thus, the search for alternative treatments for this disease is necessary. Previous studies of this group showed that systemic or i.d. injection of hydrogen sulfide (H2S) donors exerted anti-inflammatory, anti-nociceptive and anti-pruritic activity in mice skin against acute stimulus. However, the therapeutic potential of H2S donors in chronic inflammation and related chronic pruritus has not yet been established. Thus, the aims of this study are: i) to evaluate and pharmacologically characterize the protective effect of topical microemulsion or nanoemulsion containing GYY4137 (slow release H2S donor) in psoriasis model evoked by imiquimod cream in Balb/c mice; ii) to determine the involvement of IL-31 and IL-36, as well as the neuropeptides (substance P and CGRP) in psoriasis and related pruritus; iii) to evaluate the role of GYY4137 in the molecular and cellular mechanism of pruriception related with IL-31. It is expected that this study may help define news pharmacology strategies under the control of psoriasis signals and symptoms, considering the anti-inflammatory and anti-pruritic potential of H2S. (AU)