Poly(lactic-co-glycolic acid) Nanoparticles Encapsulating the Prenylated Flavonoid, Xanthohumol, Protect Corneal Epithelial Cells from Dry Eye Disease-Associated Oxidative Stress

Abstract

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.

Evaluation of the Antitumour and Antiproliferative Effect of Xanthohumol-Loaded PLGA Nanoparticles on Melanoma

“…The XN AE of the formulation was about 90% (Table I), which is a remarkable achievement when compared to recent literature reporting a AE of about 13% for XN loaded into PLGA nanoparticles [ 53 ]. Again, this shows the robustness of the nanoparticle production method.…”

The mechanisms of natural products for eye disorders by targeting mitochondrial dysfunction

“…Additionally, the chalconoid structure of Xanthohumol confers direct ROS scavenging activity, thereby broadening its therapeutic potential ( Yao et al, 2015 ). As a result, Xanthohumol has exhibited cytoprotective effects in human corneal epithelial cells and a mouse desiccating stress/scopolamine model, further validating its prospective role in ocular therapeutics ( Ghosh et al, 2021 ).…”

Nanotechnology for Topical Drug Delivery to the Anterior Segment of the Eye

“…The putative irritancy of nanoparticles was examined on New Zealand white rabbits which tolerated well the topical instillations of nanoparticles suspension to the eye; moreover, nanoparticles significantly reduced the ocular edema [71]. PLGA nanoparticles encapsulating flavonoid, xanthohumol, were found to be 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 [72]. Besides, the antioxidant compound, ferulic acid, was also loaded into PLGA nanoparticles because of its poor solubility and, therefore, low therapeutic efficacy.…”