Stattic

Psoriasis is an inflammatory autoimmune skin disease that significantly impacts quality of life. The chronic and recurrent nature of the disease can last a lifetime. Current conventional treatment options have several drawbacks, including inadequate or short-lived efficacy, issues with tolerability and adherence, practical limitations associated with topical applications and phototherapy, and significant safety and cost concerns related to systemic treatments. Generally, symptomatic treatments are applied, but complete recovery is rarely achieved. Researchers are exploring alternative treatment approaches, such as biologically based therapies. These therapies specifically target the immune mechanisms involved in psoriasis and offer advantages such as more reliable disease control, noticeable improvements in patients' quality of life, and a more favorable safety profile compared to conventional treatments. One innovative approach being investigated for the treatment of psoriasis is the use of microneedles as a transdermal drug delivery strategy, which has shown promising results in research. In this study, a biocompatible polymeric dissolving microneedle formulation composed of hyaluronic acid and sucrose was prepared using micro-molding. Microneedles were loaded with secukinumab (a human monoclonal antibody specific to IL-17A) and Stattic (a STAT3 inhibitor) for a combined treatment approach. It was expected that applying the microneedles directly to the psoriasis plaques would increase the localized drug concentration. Following in vitro characterization and cell culture studies, a psoriasis model was established in adult mice. The therapeutic effects of the microneedles containing secukinumab and Stattic (both individually and simultaneously loaded) were compared to control groups. Lesion progression was visually monitored and histologically examined following treatment. The results indicated that the secukinumab-loaded microneedles provided a more effective treatment at lower doses.

Interleukin-10 (IL-10) is a cytokine that can exert an analgesic effect on trigeminal neuropathic pain (TNP). However, its precise mechanism remains unclear. In this study, we investigated the antinociceptive effects of recombinant IL-10 (rIL-10) in a rat model of infraorbital nerve constriction. Using male Sprague-Dawley rats, we administered rIL-10 or phosphate-buffered saline to the intra-trigeminal ganglion and observed a peak analgesic effect at 4 h post-injection in the rIL-10 group. Real-time PCR demonstrated significant upregulation of the Proopiomelanocortin (Pomc) gene in rIL-10-treated rats, with immunofluorescence staining confirming increased expression of bioactive peptide β-endorphin (β-END) in the same group. In situ hybridization assay further localized Pomc expression to satellite glial cells and neurons in the trigeminal ganglion, with β-END exhibiting a similar distribution. To elucidate the signaling mechanism, we co-administered a STAT3 inhibitor, Stattic, which abolished the analgesic effect of rIL-10, suppressed Pomc upregulation, and reduced β-END expression. These findings indicate that the STAT3 pathway is a critical mediator of rIL-10-induced analgesia, with Pomc and β-END as potential molecular effectors.