Development of topical nanoformulations of tetrahydrocurcumin and tacrolimus for skin inflammation

Abstract

Atopic dermatitis (AD) a common chronic inflammatory skin disease has a prevalence of 10% to 30% in children and 2% to 10% in adults. Envisaging the limitations of current therapies it was proposed to develop a novel therapeutic regimen with minimal side effects. We herein proposed a combination of concentrated tetrahydrocurcumin (THC) lipidic nanoparticles (LNs) incorporated into an ointment alongwith tacrolimus for topical application for treatment of AD. THC-LNs were characterized for particle size, zeta potential, HRTEM, FTIR, DSC, NMR and THC-Tacro ointment was characterized for pH, rheology, occlusivity, SEM and finally stability studies were performed in accordance to ICH guidelines. Analytical method validation using HPLC was then performed for both THC and tacrolimus. The method was applied to determine the drug content, EE and dermatokinetics. Safety studies using in vitro cell line studies (cell viability, quantitative analysis, and wound healing scratch assay) were performed using human dermal fibroblast (HDF). Furthermore, in vivo skin toxicity confirmed the non-toxic effects of formulation. In vivo pharmacodynamic study in animal model of AD confirmed the efficacy of developed THC-Tacro ointment for the treatment of atopic dermatitis which was well evidenced by downregulation of inflammatory markers (TNF-and#945; and IL-6). More too above, we could successfully prepare a solubilised THC Tacro ointment using a simple scalable technique. In conclusion, the combination of THC and tacrolimus ointment through topical application provides an efficient and commercially viable alternative for dermatitis treatment, thus achieving a higher efficacy and potency with reduced toxicity. newline