Carter Renee T, Swetledge Sean, Navarro Sara, Liu Chin-C, Ineck Nikole, Lewin Andrew C, Donnarumma Fabrizio, Bodoki Ede, Stout Rhett W, Astete Carlos, Jung Jangwook P, Sabliov Cristina M
Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, United States of America.
Department of Biological and Agricultural Engineering, Louisiana State University, Baton Rouge, Louisiana, United States of America.
PLoS One. 2024 Aug 1;19(8):e0306640. doi: 10.1371/journal.pone.0306640. eCollection 2024.
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.
抗氧化疗法在预防和治疗诸如白内障等眼部疾病方面具有重要意义。尽管这是一个备受关注的活跃领域，但用于治疗白内障的抗氧化剂局部疗法却因多种眼部解剖屏障、产品稳定性和溶解性而变得复杂。将抗氧化剂包裹于聚乳酸 - 乙醇酸共聚物纳米颗粒中并进行递送，可能是应对这些挑战的一种解决方案，然而，关于它们在体外或体内的作用，人们了解甚少。我们的首要目标是研究空白及负载叶黄素的聚乳酸 - 乙醇酸共聚物纳米颗粒对体外晶状体上皮细胞活力及活性氧生成的影响。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生成情况。接下来，利用体内亚硒酸盐模型诱导啮齿动物形成白内障。用不同浓度的游离叶黄素和负载叶黄素的纳米颗粒（LNP）对眼睛进行局部治疗。监测眼睛前段变化和白内障形成情况。通过对房水样本进行液相色谱 - 质谱联用以及对晶状体进行液相色谱 - 串联质谱联用（靶向LC - MS/MS），评估纳米递送叶黄素到达眼前段的能力。在短暴露时间框架（24小时）内且浓度<0.2μg LNP/μl时，LNP对晶状体上皮细胞活力的影响极小。还观察到活性氧生成的显著减少。用相当于1278μg /mL叶黄素浓度的LNP处理的动物，白内障评分降低幅度最大。通过对房水和晶状体样本的评估，证实了叶黄素向眼前段的递送。当每日应用一次，持续一周时，局部治疗与继发性角膜炎或前葡萄膜炎的发生无关。LNP可能是治疗白内障的有效方法。
