Design, Characterization, and Efficacy of a Ferrocene￾Derivative Dermal Cream Against Skin Inflammation and Redox Imbalance

Abstract

This study evaluates the therapeutic efficacy of three functionalized organometallic formulations based on synthesized ferrocene derivatives (FMA, FCMphA, and FCMphB) as topical treatments for severe thermal burns. Severe burns trigger localized necrosis, marked cutaneous lipid peroxidation, and a Systemic Inflammatory Response Syndrome (SIRS) that severely impacts immune organs. Through a comparative analysis, we performed specific in vivo biochemical, hematological, and histopathological assays on Wistar rats, using the standard drug MEBO as a reference control. Our practical findings demonstrated that the tested ferrocene ointments significantly accelerated healing mechanics. FMA emerged as the most efficient formulation, dramatically reducing the epithelialization time to 17±5 days (compared to 29 days in untreated controls and 33 days for MEBO). At the systemic level, treatment with these derivatives induced a near￾complete normalization of the burn-induced leukocyte profile (WBC, LYM, and GRA) and effectively reversed reactive thrombocytosis. Furthermore, these formulations successfully mitigated immune organ dysregulation, restoring the burn-induced splenic hypertrophy and thymic involution back to normal physiological ranges while establishing an excellent safety profile free of hepatic or renal toxicities. Biochemically, the topical application of these compounds completely suppressed cutaneous lipid peroxidation by reducing malondialdehyde (MDA) levels and significantly restoring endogenous antioxidant defenses (GSH, SOD, and CAT) at the injury site. To elucidate these findings, an in silico molecular docking study was carried out against two regulatory protein targets: KEAP1 and MMP-9. The computational results corroborated the experimental evidence, revealing that FMA and FCMphB possess exceptional binding free energies, driving a dual mechanism of action that couples Nrf2-mediated antioxidant defense with controlled extracellular matrix remodeling. Collectively, this integrated work positions functionalized ferrocene derivatives as highly biocompatible, multi-targeted candidates for advanced burn wound therapeutics.