Suppression of cytokine gene expression and improved therapeutic efficacy of microemulsion-based tacrolimus cream for atopic dermatitis

摘要

Tacrolimus ointment being occlusive is known to give higher dermal penetration but offers limited patient acceptance in treatment of atopic dermatitis, especially in tropical countries. Hence, the aim of this study was to develop, characterize, and evaluate a microemulsion-based cream formulation of tacrolimus against ointment in hapten-induced murine model of dermatitis. Tacrolimus-loaded microemulsion having mean globule size below 25 nm was mixed with cetomacrogol cream base. The microemulsion-based cream exhibited a significantly faster drug release through semipermeable cellulose acetate membrane in comparison to commercially available ointment. The drug retention in rodent and human cadaver skin with cream was almost twofold greater in comparison to the commercially available ointment. Further, in vivo evaluation using a fluorescent marker revealed a greater and deeper accumulation of marker in skin with cream. In vivo studies in mice revealed a prompt and significant reduction in ear swelling. The reduction in inflammatory cytokine gene expression as evaluated by semiquantitative reverse transcriptase polymerase chain reaction was also significantly higher with cream. The better efficacy of cream was reflected in histopathology as well as in morphological observations at the site of application. Thus, microemulsion-based cream presents a possibility of development of an efficacious cream vehicle and a scope for dose reduction which needs to be confirmed in clinical studies.