PDF(Pubmed)
Abstract：
The most prevalent conditions among ocular surgery and COVID-19 patients are fungal eye infections, which may cause inflammation and dry eye, and may cause ocular morbidity. Amphotericin-B eye drops are commonly used in the treatment of ocular fungal infections. Lactoferrin is an iron-binding glycoprotein with broad-spectrum antimicrobial activity and is used for the treatment of dry eye, conjunctivitis, and ocular inflammation. However, poor aqueous stability and excessive nasolacrimal duct draining impede these agens\' efficiency. The aim of this study was to examine the effect of Amphotericin-B, as an antifungal against Candida albicans, Fusarium, and Aspergillus flavus, and Lactoferrin, as an anti-inflammatory and anti-dry eye, when co-loaded in triblock polymers PLGA-PEG-PEI nanoparticles embedded in P188-P407 ophthalmic thermosensitive gel. The nanoparticles were prepared by a double emulsion solvent evaporation method. The optimized formula showed particle size (177.0 ± 0.3 nm), poly-dispersity index (0.011 ± 0.01), zeta-potential (31.9 ± 0.3 mV), and entrapment% (90.9 ± 0.5) with improved ex-vivo pharmacokinetic parameters and ex-vivo trans-corneal penetrability, compared with drug solution. Confocal laser scanning revealed valuable penetration of fluoro-labeled nanoparticles. Irritation tests (Draize Test), Atomic force microscopy, cell culture and animal tests including histopathological analysis revealed superiority of the nanoparticles in reducing signs of inflammation and eradication of fungal infection in rabbits, without causing any damage to rabbit eyeballs. The nanoparticles exhibited favorable pharmacodynamic features with sustained release profile, and is neither cytotoxic nor irritating in-vitro or in-vivo. The developed formulation might provide a new and safe nanotechnology for treating eye problems, like inflammation and fungal infections.
摘要：
眼科手术和COVID-19患者中最常见的疾病是真菌性眼部感染，这可能会导致炎症和干眼症，并可能导致眼部发病。两性霉素B滴眼液通常用于治疗眼部真菌感染。乳铁蛋白是一种具有广谱抗微生物活性的铁结合糖蛋白，用于治疗干眼症，结膜炎,和眼部炎症。然而,不良的房水稳定性和过度的鼻泪管引流阻碍了这些药物的效率。这项研究的目的是检查两性霉素B的作用，作为抗白色念珠菌的抗真菌药，镰刀菌,还有黄曲霉,和乳铁蛋白，作为抗炎和抗干眼症，当共负载三嵌段聚合物PLGA-PEG-PEI纳米颗粒包埋在P188-P407眼科热敏凝胶中时。通过双乳液溶剂蒸发法制备纳米颗粒。优化后的配方显示粒径（177.0±0.3nm），多分散指数(0.011±0.01)，ζ电位（31.9±0.3mV），和包封%(90.9±0.5)，改善了离体药代动力学参数和离体角膜穿透性，与药物溶液相比。共聚焦激光扫描显示了氟标记的纳米颗粒的有价值的渗透。刺激试验（Draize试验），原子力显微镜,细胞培养和动物试验，包括组织病理学分析，揭示了纳米颗粒在减少炎症迹象和根除兔真菌感染方面的优越性。不会对兔子的眼球造成任何伤害。纳米颗粒表现出良好的药效学特征和持续释放曲线，并且在体外或体内既无细胞毒性也无刺激性。开发的配方可能为治疗眼部问题提供一种新的安全的纳米技术，比如炎症和真菌感染.
