Department of Pharmaceutical Chemistry, Sinhgad Technical Education Society's, Sinhgad College of Pharmacy, Vadgaon (bk), Pune, 411041, India.
Department of Pharmaceutics, D.Y. Patil Institute of Pharmaceutical Science and Research, Pimpri, Pune, 411018, India.
Pharm Nanotechnol. 2023;11(4):344-354. doi: 10.2174/2211738511666230310103017.
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.
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.
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.
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.
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.
酮康唑是一种含咪唑环的抗真菌药物，用于治疗系统性真菌感染。它通过阻断麦角固醇的合成起作用，麦角固醇是真菌细胞膜的必需成分。
本工作旨在构建载有透明质酸（HA）修饰的酮康唑纳米结构脂质载体（NLC）的皮肤靶向凝胶，以最小化副作用并提供控制释放。
采用乳化超声法制备 NLC，并对其进行 X 射线衍射、扫描电子显微镜和傅里叶变换红外光谱研究。然后将这些批次纳入含有 HA 的凝胶中，以方便应用。将最终制剂与市售制剂进行比较，以研究其抗真菌活性和药物扩散。
通过使用 23 因素设计，成功开发了具有理想制剂参数的酮康唑 NLC 载透明质酸制剂。开发制剂的体外释放研究表明，药物释放时间延长（长达 5 小时），而在人体尸体皮肤上进行的体外药物扩散研究表明，与市售制剂相比，药物扩散更好。此外，释放研究和扩散研究结果表明，开发制剂对白色念珠菌的抗真菌活性得到了提高。
该工作表明，酮康唑 NLC 载透明质酸修饰的凝胶提供了延长的释放。该制剂还具有良好的药物扩散和抗真菌活性，因此可以作为酮康唑局部递药的有前途的载体。
