Integrated in vitro and in vivo evaluation of ivermectin hydrogel formulation for management of scabies with pharmacological assessment

Abstract

Abstract Scabies is a contagious skin disease caused by Sarcoptes scabiei mites, posing a significant health risk, especially in poor, crowded settings. Existing treatments are facing challenges due to poor compliance and side effects, necessitating alternative therapies. Hydrogel formulations offer promise by enhancing drug release and bioavailability. This study tested a novel topical ivermectin (IVR) hydrogel for scabies, evaluating its effectiveness, anti-inflammatory, and antioxidant properties. It also assessed treatment outcomes of skin structure and its effect on animal behavior and locomotor activity. IVR hydrogel (1% w/v) was formulated and evaluated based on its physicochemical properties, in vitro release kinetics, and acaricidal activity using a contact bioassay and scanning electron microscopy (SEM). An in vivo bioassay was performed using experimentally infested rabbits treated topically with IVR hydrogel. Treatment efficacy was evaluated via histopathology, oxidative stress, inflammatory and immunological markers, and behavioral changes measured through open-field testing. The IVR gel, at a 100% concentration, achieved complete mite mortality in vitro within 10 minutes, accompanied by extensive cuticular damage. In vivo , treated rabbits exhibited marked clinical improvement, attaining a clinical score near zero (0.17) by day 21, alongside enhanced skin condition and reduced inflammation. The treatment resulted in a statistically significant reduction in inflammatory markers (TNF-α, IL-6, P< 0.001) and oxidative stress (MDA, P< 0.001) without significant alterations in specific immunoglobulin levels (IgG and IgE). Histopathological analysis confirmed improvement of skin architecture, while behavioral assessments revealed no adverse effects on animal behavior. IVR hydrogel demonstrated significant, concentration-dependent acaricidal activity, biocompatibility, and effectiveness in reducing oxidative and inflammatory damage. Based on these findings, topical ivermectin hydrogel may offer a promising platform for further investigation as a treatment modality for scabies.