Dapsone- gel as a novel platform for acne treatment: In vitro evaluation and In vivo performance and histopathological studies in acne infected mice

Abstract

The uniqueness of dapsone, 4,4′-diaminodiphenylsulfone (DPS) is attributed to its dual antimicrobial and anti-inflammatory effects. Nevertheless, DPS limited solubility in water makes its topical use in treatment of dermatological conditions limited. This study aimed to formulate and test the activity of DPS as a gel by its inclusion into a cyclodextrin ring. The interaction between DPS and methyl β-cyclodextrin (Kleptose® Crysemb) in the solution state was investigated using phase solubility technique. Aqueous solubility of DPS increased linearly as a function of the Kleptose® Crysemb concentration with a phase diagram classified as AL-type according to Higuchi and Connors. Moreover, interaction between the drug and the used cyclodextrin molecule was further investigated using differential scanning calorimetry and X-ray diffraction. The inclusion of the drug into core of the cyclodextrin molecule disrupted the crystalline nature of the drug forming crystalline form of higher solubility. The prepared complex was further incorporated in a thermo-sensitive Pluronic F127 gel, to ease the application on the skin. To assess the prepared gel anti-acne activity, in vivo testing in acne-induced inflammation mouse model was performed. DPS gel exhibited superior anti-inflammatory and healing activities compared to reference anti-acne antibiotic Aknemycin®. Additionally, the prepared DPS gel exhibited equipotent antimicrobial effect to that of reference antibiotic Aknemycin®. Our topical DPS formulation therefore provides an efficient strategy for treatment of dermatological indications, such as acne and for alternative treatment of leprosy.