{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:45:33Z","timestamp":1788284733696,"version":"build-2803163510"},"reference-count":37,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T00:00:00Z","timestamp":1645142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT), Portugal","award":["UID\/DTP\/04138\/2019 and UIDB\/04138\/2020 to iMed.ULisboa, and by national funds through FCT, I.P., Project UIDB\/00276\/2020.); principal investigator grants CEECIND\/03143\/2017 (L. M.G) & SFRH\/BD\/130476\/2017 (B.S.)"],"award-info":[{"award-number":["UID\/DTP\/04138\/2019 and UIDB\/04138\/2020 to iMed.ULisboa, and by national funds through FCT, I.P., Project UIDB\/00276\/2020.); principal investigator grants CEECIND\/03143\/2017 (L. M.G) & SFRH\/BD\/130476\/2017 (B.S.)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Neuroprotection in glaucoma using epoetin beta (EPO\u03b2) has yielded promising results. Our team has developed chitosan-hyaluronic acid nanoparticles (CS\/HA) designed to carry EPO\u03b2 into the ocular globe, improving the drug\u2019s mucoadhesion and retention time on the ocular surface to increase its bioavailability. In the present in vivo study, we explored the possibility of delivering EPO\u03b2 to the eye through subconjunctival administration of chitosan-hyaluronic acid-EPO\u03b2 (CS\/HA-EPO\u03b2) nanoparticles. Healthy Wistar Hannover rats (n = 21) were split into 7 groups and underwent complete ophthalmological examinations, including electroretinography and microhematocrit evaluations before and after the subconjunctival administrations. CS\/HA-EPO\u03b2 nanoparticles were administered to the right eye (OD), and the contralateral eye (OS) served as control. At selected timepoints, animals from each group (n = 3) were euthanized, and both eyes were enucleated for histological evaluation (immunofluorescence and HE). No adverse ocular signs, no changes in the microhematocrits (\u224845%), and no deviations in the electroretinographies in both photopic and scotopic exams were observed after the administrations (p &lt; 0.05). Intraocular pressure remained in the physiological range during the assays (11\u201322 mmHg). EPO\u03b2 was detected in the retina by immunofluorescence 12 h after the subconjunctival administration and remained detectable until day 21. We concluded that CS\/HA nanoparticles could efficiently deliver EPO\u03b2 into the retina, and this alternative was considered biologically safe. This nanoformulation could be a promising tool for treating retinopathies, namely optic nerve degeneration associated with glaucoma.<\/jats:p>","DOI":"10.3390\/md20020151","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T08:22:19Z","timestamp":1645431739000},"page":"151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Chitosan and Hyaluronic Acid Nanoparticles as Vehicles of Epoetin Beta for Subconjunctival Ocular Delivery"],"prefix":"10.3390","volume":"20","author":[{"given":"Beatriz","family":"Silva","sequence":"first","affiliation":[{"name":"CIISA\u2014Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade T\u00e9cnica, 1300-477 Lisbon, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal"},{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, 1600-277 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6799-2740","authenticated-orcid":false,"given":"L\u00eddia M.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, 1600-277 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2688-0459","authenticated-orcid":false,"given":"Berta S\u00e3o","family":"Braz","sequence":"additional","affiliation":[{"name":"CIISA\u2014Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade T\u00e9cnica, 1300-477 Lisbon, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9383-1310","authenticated-orcid":false,"given":"Esmeralda","family":"Delgado","sequence":"additional","affiliation":[{"name":"CIISA\u2014Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade T\u00e9cnica, 1300-477 Lisbon, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2011.08.001","article-title":"Understanding glaucomatous damage: Anatomical and functional data from ocular hypertensive rodent retinas","volume":"31","year":"2012","journal-title":"Prog. 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