Cinnamon oil-driven lipid nanocarrier system for topical miconazole delivery: QbD-based development and...

Lipid-based nanocarriers offer a promising approach to provide topical antifungal therapy through drug delivery enhancement and synergistic effect. Accordingly, the study was planned to develop a nano-lipid matrix incorporating an antifungal drug and a natural agent using a Quality by Design (QbD) approach. Several nanoemulsions (NEs) were developed with natural Cinnamon Essential Oil (CEO) and Miconazole (MCZ) that were optimized for selecting the best formula to be integrated with gel-base providing topical nanoemulgel (NEG) system. As far as we know, this is the first study to develop a nano-lipid matrix co-loading MCZ and CEO using a Quality by Design (QbD) approach. The optimization criteria based on the smallest particle size and maximum percentage of in vitro release. NEG was characterized for various parameters to emphasize its uniformity and appropriateness for topical delivery. Further, in vitro release over 6 h, kinetic modeling and stability analysis were executed to confirm the behavior and mechanism of the release in addition to the physical and chemical stability of the formulation. Ultimately, antifungal activity assay was conducted to check the effectiveness of CEO and MCZ combination as antifungal agents and suitability of the NEG as a nano-lipid carrier. The optimized MCZ-loaded NE was successfully developed with nanosize (222.7 nm) and high in vitro release (86.46 %) then incorporated into preformulated gel base providing MCZ-loaded NEG. It demonstrated promising physicochemical properties including; pH (5.9), viscosity (11,650 cP), spreadability (50.7 mm), extrudability (89.3 g/cm²), and drug content (99.1 %). It favorably prolonged drug release over 6 h (54.5 %) and confirmed its stability when stored over 6 months at two different conditions; room temperature and refrigerator. Eventually, MCZ-loaded NEG significantly improved the antifungal efficacy against Candida albicans, which suggest that NEG offer a synergistic platform for topical antifungal treatment.