Preclinical Evaluation of a Nanoformulated Hydrogen Sulfide-releasing Dexamethasone for Topical Treatment of Psoriasis

PURPOSE: Concerns regarding local and systemic adverse effects associated with long-term use of corticosteroids has motivated the study of new therapeutic approaches for psoriasis treatment. This study evaluated the efficacy of a novel nanoformulation loaded with a hydrogen sulfide (H₂S)-releasing dexamethasone derivative (Dexa-TBZ) in an experimental psoriasis model. METHODS: Psoriasis was induced with topical imiquimod, and mice were treated for 4 days with dexamethasone- (Dexa, control) or Dexa-TBZ-loaded nanoformulations. Erythema and scaling (assessed by a modified Psoriasis Area Severity Index), myeloperoxidase (MPO) activity, and spleen size were assessed for efficacy. RESULTS: Daily topical treatment with either Dexa or Dexa-TBZ reduced scaling and erythema, with the last most likely related to decreased inflammation, as suggested by a marked reduction in MPO activity and neutrophil infiltration. Both treatments also reduced epidermal thickening, indicating comparable local therapeutic effects. However, Dexa caused a greater reduction in circulating leukocytes and spleen size, suggesting higher systemic exposure despite topical administration. In contrast, Dexa-TBZ showed limited systemic effects. CONCLUSIONS: Although Dexa-TBZ did not demonstrate superior local efficacy, its lower systemic impact suggests an improved safety and tolerability profile, which may be advantageous for the long-term topical treatment of chronic conditions such as psoriasis.