{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T05:46:22Z","timestamp":1778046382447,"version":"3.51.4"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012429","name":"Louisiana State University, School of Veterinary Medicine","doi-asserted-by":"crossref","award":["Corp Grant"],"award-info":[{"award-number":["Corp Grant"]}],"id":[{"id":"10.13039\/100012429","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>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-<jats:italic>co<\/jats:italic>-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 &lt; 0.2 \u03bcg LNP\/\u03bcl. 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 \u03bcg \/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.<\/jats:p>","DOI":"10.1371\/journal.pone.0306640","type":"journal-article","created":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T17:27:10Z","timestamp":1722533230000},"page":"e0306640","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["The impact of lutein-loaded poly(lactic-co-glycolic acid) nanoparticles following topical application: An in vitro and in vivo study"],"prefix":"10.1371","volume":"19","author":[{"given":"Renee T.","family":"Carter","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean","family":"Swetledge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Navarro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0723-8313","authenticated-orcid":true,"given":"Chin-C.","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikole","family":"Ineck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5671-3948","authenticated-orcid":true,"given":"Andrew C.","family":"Lewin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabrizio","family":"Donnarumma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ede","family":"Bodoki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rhett W.","family":"Stout","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Astete","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5783-4549","authenticated-orcid":true,"given":"Jangwook P.","family":"Jung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6992-8304","authenticated-orcid":true,"given":"Cristina M.","family":"Sabliov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,8,1]]},"reference":[{"issue":"2","key":"pone.0306640.ref001","doi-asserted-by":"crossref","first-page":"e144","DOI":"10.1016\/S2214-109X(20)30489-7","article-title":"Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: the Right to Sight: an analysis for the Global Burden of Disease Study","volume":"9","author":"GBD 2019 Blindness and Vision Impairment Collaborators","year":"2021","journal-title":"Lancet Glob Health"},{"key":"pone.0306640.ref002","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S0140-6736(22)01839-6","article-title":"Cataracts","volume":"401","author":"MV Cicinelli","year":"2023","journal-title":"Lancet"},{"issue":"11","key":"pone.0306640.ref003","doi-asserted-by":"crossref","first-page":"4639","DOI":"10.1167\/iovs.03-0011","article-title":"Lens opacities in a rural population of southern India: the Aravind Comprehensive Eye Study","volume":"44","author":"PK Nirmalan","year":"2003","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"10094","key":"pone.0306640.ref004","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/S0140-6736(17)30544-5","article-title":"Cataracts","volume":"390","author":"Y-C Liu","year":"2017","journal-title":"The Lancet"},{"issue":"12","key":"pone.0306640.ref005","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1096\/fasebj.9.12.7672510","article-title":"Oxidative stress-induced cataract: mechanism of action","volume":"9","author":"A. 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Miller","year":"2018","journal-title":"Am J Vet Res"},{"issue":"4","key":"pone.0306640.ref042","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1006\/exer.1996.0241","article-title":"Confocal microscopy of cataracts from animal model systems: relevance to human nuclear cataract","volume":"64","author":"DL Boyle","year":"1997","journal-title":"Exp Eye Res"},{"issue":"2","key":"pone.0306640.ref043","doi-asserted-by":"crossref","first-page":"113","DOI":"10.4103\/0975-8453.75042","article-title":"Ophthalmic drug delivery system: challenges and approaches","volume":"1","author":"PB Patel","year":"2010","journal-title":"Systematic Rev Pharmacy"},{"issue":"3","key":"pone.0306640.ref044","first-page":"627","article-title":"Characterization of paracellular and aqueous penetration routes in cornea, conjunctiva and sclera","volume":"38","author":"KM Hamalainen","year":"1997","journal-title":"Inves Ophthalmol Vis 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