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Chitosan and hyaluronic acid have remarkable mucoadhesive properties and potentially enhance pre-corneal retention time after topical instillation. Bearing this in mind, we explored the possibility of delivering epoetin beta (EPO\u03b2) to the posterior segment of the eye in a chitosan-hyaluronic acid (CS\/HA-EPO\u03b2) nanoparticulate system using the topical route of administration. Complete ophthalmological examinations, electroretinography and microhematocrit evaluations were performed in Wistar Hannover (WH) rats, before and after topical administration of nanoparticles. The right eye received CS\/HA-EPO\u03b2 and the left eye received only empty nanocarriers (control). Animals were split into 6 groups and at designated timepoints, all animals from each group (n\u2009=\u20093) were euthanized and both eyes enucleated. Retinal morphology and EPO\u03b2 ocular distribution were assessed, respectively, through hematoxylin and eosin (HE) and immunofluorescence staining. After topical administration, no adverse ocular signs were noted and no significant changes either in microhematocrits nor in electroretinographies were detected. During the study, intraocular pressure (IOP) was always kept within physiological range bilaterally. No histological changes were detected in any of the ocular globes. Immunofluorescence enabled the identification of EPO\u03b2 in the retina 12\u00a0h after the administration, its presence still being detectable at day 21. In conclusion, CS\/HA nanoparticles could efficiently deliver EPO\u03b2 to the retina of WH rats after topical instillation, being considered biologically safe. Topical administration of this nanoformulation could be a\u00a0valuable tool for\u00a0retinal neuroprotection, decreasing risks associated with more invasive routes of administration, being cost effective and also increasing long-term patients\u2019 compliance.<\/jats:p>","DOI":"10.1038\/s41598-023-28845-0","type":"journal-article","created":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T19:05:49Z","timestamp":1674846349000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Topical ocular delivery of nanoparticles with epoetin beta in Wistar Hannover rats"],"prefix":"10.1038","volume":"13","author":[{"given":"Beatriz","family":"Silva","sequence":"first","affiliation":[]},{"given":"L\u00eddia M.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[]},{"given":"Berta","family":"S\u00e3o Braz","sequence":"additional","affiliation":[]},{"given":"Esmeralda","family":"Delgado","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2023,1,27]]},"reference":[{"key":"28845_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.preteyeres.2011.08.001","volume":"31","author":"M Vidal-Sanz","year":"2012","unstructured":"Vidal-Sanz, M. et al. 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