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Treatment of skin infection by dermatophytes is still limited, and the application of conventional topical formulations (ointments, creams, etc.) cause patient discomfort due to repeated administration and low efficacy. This study describes the film-forming system (FFS) hybridized with econazole (ECO)-loaded nanostructured lipid carriers (NLC) for enhanced antifungal activity against dermatophytes. We assumed that the application of NLC could effectively increase the skin permeability of ECO, thereby suppressing the growth of dermatophytes in stratum corneum as well as in epidermis. Meanwhile, ECO-NLC hybrid FFS (ECO-NLC@FFS) could increase the adhesion of ECO-NLC to the skin and prolong the antifungal activity of ECO. First, we optimized ECO-NLC, which shows nanosized particle (199 nm), high encapsulation efficiency (92.5%), and biocompatibility. ECO-NLC@FFS formed a transparent, homogeneous, and hard-to-remove film after topical application. In vitro skin permeation and deposition studies demonstrated that ECO-NLC@FFS showed 1.5-fold higher skin permeation and 3-fold higher ECO deposition in the epidermis layer than a commercial product, which resulted from the nanosized particle and its occlusion effect. And, ex vivo and in vivo antifungal activity studies confirmed that ECO-NLC@FFS improved the skin adhesion of ECO-NLC, thereby allowing ECO to be continuously exposed to the infection sited and reducing the number of applications with a single dose. These results showed that this hybrid system could be a potential for effectively improving the efficacy of antifungal agents and the patient compliance in the treatment of dermatophytes. STATEMENT OF SIGNIFICANCE: Treatment of skin infection by dermatophytes is difficult due to the inconvenience and low efficacy of conventional topical formulations. Here, we demonstrated the potential of a film-forming system (FFS) hybridized with nanostructured lipid carriers (NLC). First, we confirmed that the enhanced skin permeability of drug was improved by NLC. In addition, the hybridization of NLC with FFS improved the skin adhesion of NLC, allowing the drug to exhibit a sustained release profile and prolong antifungal activity. Given the maximized antifungal activity, this hybrid system can be used as a potential pharmaceutical technique to improve patient convenience and achieve complete treatment of skin infection., (Copyright © 2019. Published by Elsevier Ltd.)

Ticagrelor (TGL), a P2Y12 receptor antagonist, is classified as biopharmaceutics classification system (BCS) class IV drug due to its poor solubility and permeability, resulting in low oral bioavailability. Nanostructured lipid carriers (NLC) are an efficient delivery system for the improvement of bioavailability of BCS class IV drugs. Hence, we prepared TGL-loaded NLC (TGL-NLC) to enhance the oral bioavailability and antiplatelet activity of TGL with a systemic design approach. The optimized TGL-NLC with Box–Behnken design showed a small particle size of 87.6 nm and high encapsulation efficiency of 92.1%. Scanning electron microscope (SEM), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) were performed to investigate the characteristics of TGL-NLC. Furthermore, TGL-NLC exhibited biocompatible cytotoxicity against Caco-2 cells. Cellular uptake of TGL-NLC was 1.56-fold higher than that of raw TGL on Caco-2 cells. In pharmacokinetic study, the oral bioavailability of TGL-NLC was 254.99% higher than that of raw TGL. In addition, pharmacodynamic study demonstrated that the antiplatelet activity of TGL-NLC was superior to that of raw TGL, based on enhanced bioavailability of TGL-NLC. These results suggest that TGL-NLC can be applied for efficient oral absorption and antiplatelet activity of TGL. [ABSTRACT FROM AUTHOR]