Abstract
Conventional treatments for common disorders of the oral mucous membranes have great challenges, and this has motivated the development of local therapeutics with an advanced delivery platform. The present study aimed to develop a hydrogel containing clotrimazole-rosehip oil nanoethosomes (CZ-RO-NE) and to evaluate its antibacterial and antifungal efficacy and ulcer index. Optimization of CZ-RO-NE was performed by the BoxBehnken statistical design using L-alpha-phosphatidylcholine, CZ, and RO as independent variables. The optimized formulations were characterized for their rheological properties, in vitro release characteristics, and ex vivo permeability. An optimized formulation was fabricated using the thin-layer evaporation technique where the rheological property indicated non-Newtonian flow. The in vitro release profile of the formulations showed a significantly higher release (80 +/- 6.723%) from the CZ-RO-NE-embedded hydrogel compared with the marketed formulation and drug suspension (p < .05). Concurrently, the ex vivo permeation of the drug through a sheep buccal membrane was highest for the CZ-RO-NE (950 +/- 43 mu g/cm2), with a steady-state flux of 4.544 mu g/cm2. min. Finally, the antifungal effect against Candida albicans and antibacterial effect against streptococci revealed a significantly higher zone of inhibition (23 +/- 2 mm and 15 +/- 1 mm, respectively) when compared with the marketed formulation of CZ (13 +/- 2 mm and 5 +/- 2 mm, respectively). The antimicrobial efficacy of the optimized formulation was further reflected by a significant reduction in oral ulcers in experimental animals (0.5 +/- 0.39 mm) when compared with the marketed formulation of CZ (2.5 +/- 0.45). These interesting results are evidence of the effective treatment of oro-mucosal ulcers by this CZ-RO-NE hydrogel and the superior compliance of patients using the treatment.