Optimization of ethosomes for topical thymoquinone delivery for the treatment of skin acne

Abstract

The current study involved the development and optimization of ethosomes formulation for topical delivery of thymoquinone for improved therapy in skin acne. Formulation was optimized based on vesicles size, entrapment efficiency and flux by applying “3-factor 3-level Box-Behnken design”. The optimized formulation was further evaluated for “anti-microbial, anti-inflammatory, anti-acne and skin irritation activity”. The optimized formulation had shown the vesicles size of 105.2 ± 8.0 nm, entrapment efficiency of 85.30 ± 6.30% and flux of 65.40 ± 7.6 μg/cm2/h. The penetration depth of rhodamine loaded ethosomes across rat skin was traced with confocal laser microscopy and it was noted that the plain rhodamine solution (control) remained confined to few micrometers (14.4 μm) depth only into rat skin, while the rhodamine loaded ethosomes formulation penetrate deeper up to 103.5 μm depth into rat skin. Antimicrobial study exhibited that the marketed allopathic gel, prepared ethosomes formulation, and marketed herbal gel have presented zone of inhibition of 29.0 ± 1.00 mm, 20.33 ± 0.57 mm, and 15.00 ± 1.73 mm respectively against S. Epidermidis. The in vivo anti-inflammatory activity demonstrated that the application of prepared ethosomes and marketed diclofenac gel formulation resulted in an inhibition of rat paw edema by 80.74% and 84.61% respectively in Wistar rats. Anti-acne study demonstrated that the developed ethosomes formulation had shown considerable effect on sebaceous glands units by reducing its glands number and size. Further skin irritation study revealed that the developed formulation was safe, less irritant and well tolerable formulation for topical delivery. It was concluded that the developed thymoquinone loaded ethosomes formulation can be used as an effective treatment option for acne vulgaris and various skin disorders.