Topical delivery of artemisone, clofazimine and decoquinate encapsulated in vesicles and their in vitro efficacy against Mycobacterium tuberculosis

Abstract

Vesicles are widely investigated as carrier systems for active pharmaceutical ingredients (APIs). For topical delivery, they are especially effective since they create a “depot-effect” thereby concentrating the APIs in the skin. Artemisone, clofazimine and decoquinate were selected as a combination therapy for the topical treatment of cutaneous tuberculosis. Delivering APIs into the skin presents various challenges. However, utilising niosomes, liposomes and transferosomes as carrier systems may circumvent these challenges. Vesicles containing 1% of each of the three selected APIs were prepared using the thin-film hydration method. Isothermal calorimetry, differential scanning calorimetry and hot-stage microscopy indicated no to minimal incompatibility between the APIs and the vesicle components. Encapsulation efficiency was higher than 85% for all vesicle dispersions. Vesicle stability decreased and size increased with an increase in API concentration; and ultimately, niosomes were found the least stable of the different vesicle types. Skin diffusion studies were subsequently conducted for 12 h on black human female skin utilising vertical Franz diffusion cells. Transferosomes and niosomes delivered the highest average concentrations of clofazimine and decoquinate into the skin, whereas artemisone was not detected and no APIs were present in the receptor phase. Finally, efficacy against tuberculosis was tested against the Mycobacterium tuberculosis H37Rv laboratory strain. All the dispersions depicted some activity, surprisingly even the blank vesicles portrayed activity. However, the highest percentage inhibition (52%) against TB was obtained with niosomes containing 1% clofazimine