PDF(Pubmed)
Abstract：
Antioxidant therapies are of interest in the prevention and management of ocular disorders such as cataracts. Although an active area of interest, topical therapy with antioxidants for the treatment of cataracts is complicated by multiple ocular anatomical barriers, product stability, and solubility. Entrapment and delivery of antioxidants with poly(lactic-co-glycolic acid) nanoparticles is a possible solution to these challenges, however, little is known regarding their effects in vitro or in vivo. Our first aim was to investigate the impact of blank and lutein loaded PLGA nanoparticles on viability and development of reactive oxygen species in lens epithelial cells in vitro. Photo-oxidative stress was induced by ultraviolet light exposure with cell viability and reactive oxygen species monitored. Next, an in vivo, selenite model was utilized to induce cataract formation in rodents. Eyes were treated topically with both free lutein and lutein loaded nanoparticles (LNP) at varying concentrations. Eyes were monitored for the development of anterior segment changes and cataract formation. The ability of nanodelivered lutein to reach the anterior segment of the eye was evaluated by liquid chromatography coupled to mass spectrometry of aqueous humor samples and liquid chromatography coupled to tandem mass spectrometry (targeted LC-MS/MS) of lenses. LNP had a minimal impact on the viability of lens epithelial cells during the short exposure timeframe (24 h) and at concentrations < 0.2 μg LNP/μl. A significant reduction in the development of reactive oxygen species was also noted. Animals treated with LNPs at an equivalent lutein concentration of 1,278 μg /mL showed the greatest reduction in cataract scores. Lutein delivery to the anterior segment was confirmed through evaluation of aqueous humor and lens sample evaluation. Topical treatment was not associated with the development of secondary keratitis or anterior uveitis when applied once daily for one week. LNPs may be an effective in the treatment of cataracts.
摘要：
抗氧化剂疗法在预防和管理眼部疾病如白内障方面是令人感兴趣的。虽然是一个活跃的兴趣领域，用抗氧化剂治疗白内障的局部治疗并发多个眼解剖障碍，产品稳定性,和溶解度。用聚(乳酸-共-乙醇酸)纳米颗粒包封和递送抗氧化剂是这些挑战的可能解决方案,然而,关于它们在体外或体内的作用知之甚少。我们的第一个目的是研究空白和叶黄素负载的PLGA纳米颗粒对体外晶状体上皮细胞中活性氧簇的活力和发育的影响。通过紫外线照射诱导光氧化应激，并监测细胞活力和活性氧。接下来,体内，亚硒酸盐模型用于诱导啮齿动物的白内障形成。用不同浓度的游离叶黄素和装载叶黄素的纳米颗粒(LNP)局部处理眼睛。监测眼睛的前节变化和白内障形成的发展。通过与房水样品的质谱联用的液相色谱和与晶状体的串联质谱联用的液相色谱(靶向LC-MS/MS)来评估纳米递送的叶黄素到达眼前段的能力。LNP在短暴露时间范围内(24小时)和浓度<0.2μgLNP/μl时对晶状体上皮细胞的活力影响最小。还注意到活性氧的发展显着减少。用相同叶黄素浓度为1,278μg/mL的LNP处理的动物显示白内障评分的最大降低。通过评估房水和晶状体样品评估来确认叶黄素向前段的递送。每天一次，持续一周，局部治疗与继发性角膜炎或前葡萄膜炎的发展无关。LNP可有效治疗白内障。
