Development of tacrolimus-loaded transfersomes for deeper skin penetration enhancement and therapeutic effect improvement in vivo

The aims of this study were to prepare novel transfersomes (TFs) for tacrolimus to treat atopic dermatitis, and to observe the therapeutic effects on mice atopic dermatitis, as compared to commercial tacrolimus ointment (Protopic®) and liposomes-gel. Different kinds of surfactants—sodium cholate, Tween 80 and Span 80 were investigated to prepare TFs respectively. TFs-Tween 80 was selected as the optimal carrier owing to the best deformability and the highest drug retentions. Entrapment efficiency and diameter were also evaluated. The optimized TFs were further made into gel and in vitro drug release of TFs-gel after 24 h was higher than the commercial ointment. Cumulative drug release from TFs-gel after 12 h in vitro was 37.6%. The optimized TFs-gel illustrated remarkably highest drug skin retentions when compared with liposomes-gel and commercial ointment in vivo skin retention experiments. The amounts of tacrolimus in epidermis and dermis from TFs-gel were 3.8 times and 4.2 times respectively as much as ointment, while liposomes-gel was only 1.7 times and 1.4 times respectively as compared to ointment. Topical application of TFs-gel displayed the best therapeutic effect on mice atopic dermatitis induced by repeated topical application of 2,4-dinitrofluorobenzene. Thus TFs displayed superior performance and effective skin target for topical delivery of tacrolimus.