Sadozai Sajid Khan, Khan Saeed Ahmad, Baseer Abdul, Ullah Rooh, Zeb Alam, Schneider Marc
Department of Pharmacy, Kohat University of Science and Technology, Kohat, Pakistan.
Department of Pharmacy, Abasyn University, Peshawar, Pakistan.
Front Pharmacol. 2022 Jul 8;13:909851. doi: 10.3389/fphar.2022.909851. eCollection 2022.
Ketoconazole is commonly used in the treatment of topical fungal infections. The therapy requires frequent application for several weeks. Systemic side effects, allergic reactions, and prolonged treatment are often associated with non-compliance and therapy failure. Hence, we developed an optimized topical antifungal gel that can prolong the release of drug, reduce systemic absorption, enhance its therapeutic effect, and improve patient compliance. Ketoconazole-loaded PLGA nanoparticles were prepared by the emulsion/solvent evaporation method and were characterized with respect to colloidal properties, surface morphology, and drug entrapment efficiency. The optimized ketoconazole-loaded PLGA nanoparticles and commercially available silver nanoparticles were incorporated into a Carbopol 934P-NF gel base. This arrangement was characterized and compared with commercially available 2% ketoconazole cream to assess physical characteristics of the gel, drug release, skin permeation and retention, and studies on Wister male albino rats. The results showed that polymeric PLGA nanoparticles were very effective in extending the release of ketoconazole in our optimized formulation. Nanoparticles were smooth, spherical in shape, and below 200 nm in size which is consistent with the data obtained from light scattering and SEM images. The data showed that our gel formulation could strongly reduce drug permeation through the skin, and more than 60% of the drug was retained on the upper surface of the skin in contrast to 38.42% of the commercial cream. The studies showed that gel formulation could effectively treat the infection. This study demonstrates that our topical gel could be effective in sustaining the release of drug and suggests its potential use as a possible strategy to combat antifungal-resistant .
酮康唑常用于治疗局部真菌感染。该疗法需要连续数周频繁用药。全身副作用、过敏反应以及长期治疗往往与患者依从性差和治疗失败有关。因此，我们开发了一种优化的局部抗真菌凝胶，它可以延长药物释放时间，减少全身吸收，增强治疗效果，并提高患者依从性。采用乳液/溶剂蒸发法制备了负载酮康唑的聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒，并对其胶体性质、表面形态和药物包封率进行了表征。将优化后的负载酮康唑的PLGA纳米颗粒和市售银纳米颗粒掺入卡波姆934P-NF凝胶基质中。对这种制剂进行了表征，并与市售2%酮康唑乳膏进行比较，以评估凝胶的物理特性、药物释放、皮肤渗透和滞留情况，并在雄性白化Wistar大鼠上进行了研究。结果表明，在我们优化的制剂中，聚合物PLGA纳米颗粒在延长酮康唑释放方面非常有效。纳米颗粒表面光滑，呈球形，尺寸小于200 nm，这与光散射和扫描电子显微镜（SEM）图像获得的数据一致。数据显示，我们的凝胶制剂可显著减少药物透过皮肤的渗透，与市售乳膏38.42%的药物保留率相比，超过60%的药物保留在皮肤表面。研究表明，凝胶制剂可有效治疗感染。这项研究表明，我们的局部凝胶在持续释放药物方面可能有效，并表明其作为对抗耐药性真菌感染的一种可能策略具有潜在用途。
