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Article

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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Graduate Program in Biochemistry and Molecular Biology, Health Sciences Campus, Loyola University Chicago, Maywood, IL 60153, USA
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Visual Neurobiology and Signal Transduction Laboratory, Department of Ophthalmology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA
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Research Service, Edward Hines Jr. VA Hospital, Hines, IL 60141, USA
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Research & Development Division, Experimentica Ltd., 70211 Kuopio, Finland
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Graduate Program in Neuroscience, Health Sciences Campus, Loyola University Chicago, Maywood, IL 60153, USA
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Department of Molecular Pharmacology & Neuroscience, Loyola University Chicago, Maywood, IL 60153, USA
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State Research Institute Centre for Innovative Medicine, Santariskiu 5, LT-08406 Vilnius, Lithuania
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Department of Ophthalmology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA
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Research & Development Division, UAB Experimentica, LT-10223 Vilnius, Lithuania
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North Texas Eye Research Institute, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX 76107, USA
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Author to whom correspondence should be addressed.
Academic Editors: Anuj Chauhan, Laurence Fitzhenry, Ana Paula Serro and Montse Mitjans Arnal
Pharmaceutics 2021, 13(9), 1362; https://doi.org/10.3390/pharmaceutics13091362
Received: 5 May 2021 / Revised: 12 August 2021 / Accepted: 24 August 2021 / Published: 30 August 2021
(This article belongs to the Special Issue Recent Advances in Ophthalmic Drug Delivery)
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. View Full-Text
Keywords: ocular surface disease; dry eye disease; antioxidant; xanthohumol; drug delivery; PLGA nanoparticles ocular surface disease; dry eye disease; antioxidant; xanthohumol; drug delivery; PLGA nanoparticles
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MDPI and ACS Style

Ghosh, A.K.; Thapa, R.; Hariani, H.N.; Volyanyuk, M.; Ogle, S.D.; Orloff, K.A.; Ankireddy, S.; Lai, K.; Žiniauskaitė, A.; Stubbs, E.B., Jr.; Kalesnykas, G.; Hakkarainen, J.J.; Langert, K.A.; Kaja, S. Poly(lactic-co-glycolic acid) Nanoparticles Encapsulating the Prenylated Flavonoid, Xanthohumol, Protect Corneal Epithelial Cells from Dry Eye Disease-Associated Oxidative Stress. Pharmaceutics 2021, 13, 1362. https://doi.org/10.3390/pharmaceutics13091362

AMA Style

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. Poly(lactic-co-glycolic acid) Nanoparticles Encapsulating the Prenylated Flavonoid, Xanthohumol, Protect Corneal Epithelial Cells from Dry Eye Disease-Associated Oxidative Stress. Pharmaceutics. 2021; 13(9):1362. https://doi.org/10.3390/pharmaceutics13091362

Chicago/Turabian Style

Ghosh, Anita K., Rubina Thapa, Harsh N. Hariani, Michael Volyanyuk, Sean D. Ogle, Karoline A. Orloff, Samatha Ankireddy, Karen Lai, Agnė Žiniauskaitė, Evan B. Stubbs Jr., Giedrius Kalesnykas, Jenni J. Hakkarainen, Kelly A. Langert, and Simon Kaja. 2021. "Poly(lactic-co-glycolic acid) Nanoparticles Encapsulating the Prenylated Flavonoid, Xanthohumol, Protect Corneal Epithelial Cells from Dry Eye Disease-Associated Oxidative Stress" Pharmaceutics 13, no. 9: 1362. https://doi.org/10.3390/pharmaceutics13091362

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