FORMULATION AND EVALUATION OF A CURCUMIN THYMOQUINONE–RESVERATROL-LOADED NANOEMULSION AND NANOEMULGEL FOR TOPICAL MANAGEMENT OF PSORIASIS AND ACNE VULGARIS

Abstract

Background: Curcumin, thymoquinone and resveratrol suffer from the issues of limited aqueous solubility which makes it challenging to be delivered as a topical agent. This work was designed to develop a nanoemulsion co-loaded with these three bioactives and to develop the nanoemulgel and evaluate its skin permeation and biological activity in vivo. Methods: Nine nanoemulsion formulations were screened after performing a pseudo-ternary phase-diagram analysis and excipient-solubility assessment along with a simultaneously developed UPLC assay. The chosen formulation was then incorporated into a gel formulation of Carbopol 940 and its physicochemical, ex vivo skin delivery, antimicrobial activity, cell based responses, in vivo activity in a mouse model of psoriasis like inflammation and storage stability was assessed. Results: The selected nanoemulsion (10% Capryol 90, 35% Tween 80–Transcutol P [2:1] and 55% water) had a mean droplet size of 92.4 ± 2.7 nm, polydispersity index of 0.214 ± 0.018, zeta potential of −18.6 ± 1.9 mV and transmittance of 98.6 ± 0.4%. The amount of curcumin, thymoquinone and resveratrol in nanoemulgel was 99.1 ± 0.8%, 99.5 ± 0.7% and 99.0 ± 0.9% respectively. At 24 h, the corresponding skin deposition values were 51.8 ± 3.9, 58.7 ± 4.2 and 45.6 ± 3.5 µg/g, representing 2.64-, 2.37- and 2.55-fold increases over the conventional gel. The inhibition zone values of Cutibacterium acnes and Staphylococcus aureus were 23.4 ± 1.2 and 20.8 ± 1.0 mm, respectively. The nanoemulgel group PASI score was 2.8 ± 0.6 on day 7 and for the disease-control group, it was 9.2 ± 0.7 (reported p < 0.001). After 6 months storage at 40°C and 75%RH, the bioactive contents of these samples were still found to be not less than 94%. Conclusion: The tri-bioactive nanoemulgel improved the deposition of drug on skin when compared to conventional gel and exhibited promising activity on the preclinical models studied. Further research is needed to establish the clinical efficacy, stability and safety of long term use of the product.