Poly(lactic-co-glycolic acid) Nanoparticles Encapsulating the Prenylated Flavonoid, Xanthohumol, Protect Corneal Epithelial Cells from Dry Eye Disease-Associated Oxidative Stress.
Poly(lactic-co-glycolic acid) Nanoparticles Encapsulating the Prenylated Flavonoid, Xanthohumol, Protect Corneal Epithelial Cells from Dry Eye Disease-Associated Oxidative Stress.
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DOI：
10.3390/pharmaceutics13091362
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发表时间：
2021-08-30
期刊：
影响因子：
5.4
通讯作者：
Kaja S
中科院分区：
文献类型：
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作者：
Ghosh AK;Thapa R;Hariani HN;Volyanyuk M;Ogle SD;Orloff KA;Ankireddy S;Lai K;Žiniauskaitė A;Stubbs EB Jr;Kalesnykas G;Hakkarainen JJ;Langert KA;Kaja S
氧化应激是干眼病病理生理学进展的已知贡献者，并且先前的研究已经表明，抗氧化剂干预是一种有前途的治疗方法，可以减轻疾病负担并减缓疾病进展。在这项研究中，我们评估了天然存在的异戊二烯化查耳酮，黄腐酚，在干眼病的临床前模型的药理学疗效。黄腐酚通过促进II相抗氧化酶的转录起作用。在这项研究中，黄腐酚防止叔丁基过氧化氢诱导的人角膜上皮（HCE-T）细胞的细胞活力的损失，在剂量依赖性的方式，并导致转录因子核因子红细胞2相关因子2（Nrf2），第二阶段内源性抗氧化酶的主调节因子的表达显着增加。体外实验表明，黄腐酚包封的聚乳酸-羟基乙酸纳米粒（PLGA NP）具有抗氧化作用，并在干眼病的小鼠干燥应激/东莨菪碱模型中显著降低眼表损伤和角膜上皮细胞中氧化应激相关的DNA损伤。PLGA NP代表了用于将疏水性小分子递送至眼表面的安全且有效的药物递送载体。以最小化滴注频率为目标的NP基抗氧化剂制剂的优化可能代表干眼病和相关眼表疾病的未来治疗选择。
Oxidative stress is a known contributor to the progression of dry eye disease pathophysiology, and previous studies have shown that antioxidant intervention is a promising therapeutic approach to reduce the disease burden and slow disease progression. In this study, we evaluated the pharmacological efficacy of the naturally occurring prenylated chalconoid, xanthohumol, in preclinical models for dry eye disease. Xanthohumol acts by promoting the transcription of phase II antioxidant enzymes. In this study, xanthohumol prevented tert-butyl hydroperoxide-induced loss of cell viability in human corneal epithelial (HCE-T) cells in a dose-dependent manner and resulted in a significant increase in expression of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), the master regulator of phase II endogenous antioxidant enzymes. Xanthohumol-encapsulating poly(lactic-co-glycolic acid) nanoparticles (PLGA NP) were cytoprotective against oxidative stress in vitro, and significantly reduced ocular surface damage and oxidative stress-associated DNA damage in corneal epithelial cells in the mouse desiccating stress/scopolamine model for dry eye disease in vivo. PLGA NP represent a safe and efficacious drug delivery vehicle for hydrophobic small molecules to the ocular surface. Optimization of NP-based antioxidant formulations with the goal to minimize instillation frequency may represent future therapeutic options for dry eye disease and related ocular surface disease.