Co-delivery of Tacrolimus and Thymoquinone topically by Nanostructured lipid carriers gel for enhanced efficacy against imiquimod-induced psoriasis in Balb/c mice

Abstract

The primary objective of this current investigation is to evaluate the antipsoriatic potential of a novel nanogel delivery system that co-encapsulates tacrolimus and thymoquinone within nanostructured lipid carriers (NLCs). Therefore, TAC-THQ-NLCs-gel was formulated by emulsification solvent-evaporation technique and evaluated for their potential in improving skin permeation, skin bioavailability, skin safety, and therapeutic efficacy in imiquimod-induced psoriasis in mice plaque model. The ex-vivo skin permeation study shows 2.51- and 2.12-folds higher permeation for TAC-THQ-NLCs-gel as compared to TAC-THQ-suspension-gel, also the permeation enhancement mechanism of NLCs gel was confirmed using FTIR and DSC. Further skin retention study shows 2.87- and 2.36-fold improvement in retention of the drug as compared to free drug gel formulation. Further, the dermatokinetic study shows 2.78 and 2.37 folds higher Cmax and 2.93- and 2.40-fold higher AUC (area under the curve) for TAC and THQ respectively as compared to free drugs gel. The results of the in-vivo skin compliance study suggested that the fabricated TAC-THQ-NLCs-gel was safe for skin delivery. Furthermore, TAC-THQ-NLCS-gel represented much better amelioration of psoriasis in Balb/c mice, with a cumulative PASI score reduction of 83.80% as compared to 57.14% for free drugs gel after the end of treatment. In addition, the insignificant changes in the histology of the skin, spleen, and liver further confirm the efficacy and safety of the developed TAC-THQ-NLCs-gel. Based on these observations, it can be inferred that TAC-THQ-NLCs-gel holds promise as a combined treatment approach for managing psoriasis topically.