Quality-by-Design Approach for Investigating the Efficacy of Tacrolimus and Hyaluronic Acid-Loaded Ethosomal Gel in Dermal Management of Psoriasis: In Vitro, Ex Vivo, and In Vivo Evaluation.

Abstract

Psoriasis is an auto-immune condition with high keratinocyte hyperproliferation due to lower p53 and p22 levels. Tacrolimus, an immune suppressor, is considered one of the most effective drugs in suppressing psoriasis. Systematic administration of tacrolimus often leads to challenging side effects, namely increased infection risk, renal toxicity, neurological symptoms such as tremors and headaches, gastrointestinal disturbances, hypertension, skin-related problems, etc. To address this, a nanocarrier-based formulation of tacrolimus along with inclusion of hyaluronic acid was developed. The optimization and formulation of ethosomes via the ethanol injection technique were done based on the Box-Behnken experimental design. The results revealed hyaluronic acid-based tacrolimus ethosomes (HA-TAC-ETH) had nanometric vesicle size (315.7 ± 2.2nm), polydispersity index (PDI) (0.472 ± 0.07), and high entrapment efficiency (88.3 ± 2.52%). The findings of drug release and skin permeation showed sustained drug release with increased dermal flux and enhancement ratio. The effectiveness of HA-TAC-ETH was confirmed in an imiquimod (5%)-prompted psoriasis model. The skin irritation score and Psoriasis Area and Severity Index (PASI) score indicated that HA-TAC-ETH gel has validated a decline in the entire factors (erythema, edema, and thickness) in the imiquimod-induced psoriasis model in contrast with TAC-ETH gel and TAC ointment. The fabricated HA-TAC-ETH opt gel proved to be safe and effective in in vivo studies and could be employed to treat psoriasis further.