Topical ocular delivery of nanoparticles with epoetin beta in Wistar Hannover rats
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10451/59204 |
Resumo: | Topical instillation of drugs targeting the posterior ocular segment is an expanding area of research. 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 (EPOβ) to the posterior segment of the eye in a chitosan-hyaluronic acid (CS/HA-EPOβ) 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-EPOβ 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 = 3) were euthanized and both eyes enucleated. Retinal morphology and EPOβ 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 EPOβ in the retina 12 h after the administration, its presence still being detectable at day 21. In conclusion, CS/HA nanoparticles could efficiently deliver EPOβ to the retina of WH rats after topical instillation, being considered biologically safe. Topical administration of this nanoformulation could be a valuable tool for retinal neuroprotection, decreasing risks associated with more invasive routes of administration, being cost effective and also increasing long-term patients’ compliance. |
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Topical ocular delivery of nanoparticles with epoetin beta in Wistar Hannover ratsTopical instillation of drugs targeting the posterior ocular segment is an expanding area of research. 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 (EPOβ) to the posterior segment of the eye in a chitosan-hyaluronic acid (CS/HA-EPOβ) 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-EPOβ 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 = 3) were euthanized and both eyes enucleated. Retinal morphology and EPOβ 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 EPOβ in the retina 12 h after the administration, its presence still being detectable at day 21. In conclusion, CS/HA nanoparticles could efficiently deliver EPOβ to the retina of WH rats after topical instillation, being considered biologically safe. Topical administration of this nanoformulation could be a valuable tool for retinal neuroprotection, decreasing risks associated with more invasive routes of administration, being cost effective and also increasing long-term patients’ compliance.This research was funded by the Fundação para a Ciência e a Tecnologia (FCT), Portugal (UID/DTP/04138/2019 and UIDB/04138/2020 to iMed.ULisboa, and is has also been funded by national funds through FCT-Fundação para a Ciência e a Tecnologia, I.P., under the Project UIDB/00276/2020 for CIISA and the Project LA/P/0059/2020 for AL4AnimalS); principal investigator grants CEECIND/03143/2017 (L. M. Gonçalves) and Beatriz Silva thanks to FCT for her fellowship SFRH/BD/130476/2017.Springer NatureRepositório da Universidade de LisboaSilva, BeatrizGonçalves, LídiaBraz, Berta SãoDelgado, Esmeralda2023-09-11T15:50:12Z2023-01-272023-02-27T14:09:38Z2023-01-27T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/59204engSilva B, Gonçalves LM, São Braz B, Delgado E. Topical ocular delivery of nanoparticles with epoetin beta in Wistar Hannover rats. Sci Rep [Internet]. 27 de janeiro de 2023;13(1):1559. Disponível em: https://www.nature.com/articles/s41598-023-28845-02045-2322cv-prod-314757210.1038/s41598-023-28845-0info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:04:02Zoai:repositorio.ul.pt:10451/59204Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:06:59.110243Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Topical ocular delivery of nanoparticles with epoetin beta in Wistar Hannover rats |
title |
Topical ocular delivery of nanoparticles with epoetin beta in Wistar Hannover rats |
spellingShingle |
Topical ocular delivery of nanoparticles with epoetin beta in Wistar Hannover rats Silva, Beatriz |
title_short |
Topical ocular delivery of nanoparticles with epoetin beta in Wistar Hannover rats |
title_full |
Topical ocular delivery of nanoparticles with epoetin beta in Wistar Hannover rats |
title_fullStr |
Topical ocular delivery of nanoparticles with epoetin beta in Wistar Hannover rats |
title_full_unstemmed |
Topical ocular delivery of nanoparticles with epoetin beta in Wistar Hannover rats |
title_sort |
Topical ocular delivery of nanoparticles with epoetin beta in Wistar Hannover rats |
author |
Silva, Beatriz |
author_facet |
Silva, Beatriz Gonçalves, Lídia Braz, Berta São Delgado, Esmeralda |
author_role |
author |
author2 |
Gonçalves, Lídia Braz, Berta São Delgado, Esmeralda |
author2_role |
author author author |
dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
dc.contributor.author.fl_str_mv |
Silva, Beatriz Gonçalves, Lídia Braz, Berta São Delgado, Esmeralda |
description |
Topical instillation of drugs targeting the posterior ocular segment is an expanding area of research. 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 (EPOβ) to the posterior segment of the eye in a chitosan-hyaluronic acid (CS/HA-EPOβ) 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-EPOβ 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 = 3) were euthanized and both eyes enucleated. Retinal morphology and EPOβ 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 EPOβ in the retina 12 h after the administration, its presence still being detectable at day 21. In conclusion, CS/HA nanoparticles could efficiently deliver EPOβ to the retina of WH rats after topical instillation, being considered biologically safe. Topical administration of this nanoformulation could be a valuable tool for retinal neuroprotection, decreasing risks associated with more invasive routes of administration, being cost effective and also increasing long-term patients’ compliance. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-09-11T15:50:12Z 2023-01-27 2023-02-27T14:09:38Z 2023-01-27T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/59204 |
url |
http://hdl.handle.net/10451/59204 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Silva B, Gonçalves LM, São Braz B, Delgado E. Topical ocular delivery of nanoparticles with epoetin beta in Wistar Hannover rats. Sci Rep [Internet]. 27 de janeiro de 2023;13(1):1559. Disponível em: https://www.nature.com/articles/s41598-023-28845-0 2045-2322 cv-prod-3147572 10.1038/s41598-023-28845-0 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Springer Nature |
publisher.none.fl_str_mv |
Springer Nature |
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