Formulation and Development of Hyaluronic Acid based Gel with Ketoconazole-Loaded Nanostructured Lipid Carriers in Fungal Infection

Abstract

Background: Ketoconazole is an imidazole ring containing antifungal agent used in the treatment of systemic fungal infections. It acts by blocking the synthesis of ergosterol, an essential component of the fungal cell membrane.

Objective: The purpose of this work is to construct skin targeting ketoconazole nanostructured lipid carriers (NLCs) loaded hyaluronic acid (HA) modified gel to minimize side effects and provide a controlled release.

Methods: The NLCs were prepared using emulsion sonication method and their optimized batches were characterized for X-ray diffraction, scanning electron microscopy and fourier transform infrared spectroscopy study. These batches were then incorporated into HA containing gel for convenient application. The final formulation was compared with the marketed formulation for studying its antifungal activity and drug diffusion.

Results: Ketoconazole NLCs loaded hyaluronic acid formulation was successfully developed with desirable formulation parameters by using 23 Factorial design. In vitro release study of developed formulation showed prolonged drug release (up to 5 hrs) while ex vivo drug diffusion study on human cadaver skin showed better drug diffusion as compared with marketed formulation. Moreover, the release study and diffusion study results reflected the improvement of antifungal activity of the developed formulation against Candida albicans.

Conclusion: The work suggests that ketoconazole NLCs loaded HA modified gel provides prolonged release. The formulation also has good drug diffusion and antifungal activity and thus can act as a promising carrier for topical delivery of ketoconazole.

Keywords: Ketoconazole; NLCs; antifungal activity; emulsion sonication method; fungal infection; hyaluronic acid; topical.