Kumar Gourav, Kalita Aians H, Ahmed Jabin, Saxena Shubhi, Sharma Subhi, Mehta Astha, Sharma Amit, Das Kurmi Balak, Das Gupta Ghanshyam, Thakur Shubham
Department of Pharmaceutics, ISF College of Pharmacy, Moga, 142001, Punjab, India.
Department of Quality Assurance, ISF College of Pharmacy, Moga, 142001, Punjab, India.
Naunyn Schmiedebergs Arch Pharmacol. 2025 May 17. doi: 10.1007/s00210-025-04268-8.
Fungal keratitis (FK) is a serious, vision-threatening ocular infection caused by various fungal species. Poor outcomes often leave patients with corneal opacification and loss of vision, occasionally advancing to enucleation due to the lack of effective treatment options. Several health agencies have outlined topical antifungal medications as first-line approaches in treating FK. Commercially available topical antifungal formulations are natamycin (5%), voriconazole (1%), fluconazole (0.2-0.5%), itraconazole (1%), and amphotericin B (0.15%). Different molecules remain effective against various species of fungus. However, amphotericin B (Am-B) is a broad-spectrum antifungal agent, and when all other medications fail, Am-B is the only drug of choice. However, its clinical application is hindered due to the non-availability of ophthalmic marketed products because of its poor pharmaco-technical factors (low solubility, poor permeation, unstable in solutions of pH 3-10, etc.). Therefore, clinicians are forced to use Am-B injectables off-label by preparing the diluted concentrations of Am-B for ophthalmic use. These solutions have limitations, viz., poor stability, rapid precorneal clearance, and limited drug retention. Thus, it is highly essential for the development of advanced ophthalmic novel drug delivery systems so that the therapeutic and toxic profiles of drugs might improve. Therefore, the present review explores the limitations of conventional Am-B therapy and highlights the transformative potential of nanocarrier-based delivery systems in FK management. It discusses various nanocarrier strategies, their pharmacokinetics, and preclinical and clinical advancements. By bridging the gap between conventional treatments and modern nanotechnology, this review underscores the potential of nanocarriers to revolutionize FK treatment, offering more effective and patient-friendly therapeutic solutions.
真菌性角膜炎(FK)是一种由多种真菌引起的严重的、威胁视力的眼部感染。治疗效果不佳常常导致患者角膜混浊和视力丧失,由于缺乏有效的治疗选择,偶尔会发展到眼球摘除。几家卫生机构已将局部抗真菌药物列为治疗FK的一线方法。市售的局部抗真菌制剂有那他霉素(5%)、伏立康唑(1%)、氟康唑(0.2 - 0.5%)、伊曲康唑(1%)和两性霉素B(0.15%)。不同的分子对各种真菌都有疗效。然而,两性霉素B(Am - B)是一种广谱抗真菌剂,当所有其他药物都无效时,Am - B是唯一的选择药物。然而,由于其药学技术因素不佳(低溶解度、渗透性差、在pH 3 - 10的溶液中不稳定等),市面上没有眼科用产品,其临床应用受到阻碍。因此,临床医生被迫超说明书使用Am - B注射剂,通过配制稀释浓度的Am - B用于眼科。这些溶液有局限性,即稳定性差、角膜前清除快和药物滞留有限。因此,开发先进的眼科新型药物递送系统非常必要,这样药物的治疗和毒性特征可能会得到改善。因此,本综述探讨了传统Am - B疗法的局限性,并强调了基于纳米载体的递送系统在FK治疗中的变革潜力。它讨论了各种纳米载体策略、它们的药代动力学以及临床前和临床进展。通过弥合传统治疗与现代纳米技术之间的差距,本综述强调了纳米载体在FK治疗方面进行变革的潜力,提供了更有效且对患者更友好的治疗方案。
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