Topical Administration of a Nanoformulation of Chitosan-Hyaluronic Acid-Epoetin Beta in a Rat Model of Glaucoma

The present work investigates the effects of chitosan-hyaluronic acid-epoetin beta (CS/HA-EPOβ) nanoparticles after topical ocular administration in a rat glaucoma model. Wistar Hannover rats (<i>n</i> = 24) were submitted to a complete ophthalmological examination and electroretinograph...

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Main Authors: Beatriz Silva, Lídia M. Gonçalves, Berta São Braz, Esmeralda Delgado
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Pharmaceuticals
Subjects:
Online Access:https://www.mdpi.com/1424-8247/16/2/164
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author Beatriz Silva
Lídia M. Gonçalves
Berta São Braz
Esmeralda Delgado
author_facet Beatriz Silva
Lídia M. Gonçalves
Berta São Braz
Esmeralda Delgado
author_sort Beatriz Silva
collection DOAJ
description The present work investigates the effects of chitosan-hyaluronic acid-epoetin beta (CS/HA-EPOβ) nanoparticles after topical ocular administration in a rat glaucoma model. Wistar Hannover rats (<i>n</i> = 24) were submitted to a complete ophthalmological examination and electroretinography, followed by glaucoma induction in their right eye on day 1 of the study. Treatment group (T) received CS/HA-EPOβ nanocarriers (<i>n</i> = 12), while the control group (C) received only empty ones. Electroretinography was repeated on day 3 (<i>n</i> = 24) and before euthanasia on day 7 (<i>n</i> = 8), 14 (<i>n</i> = 8), and 21 (<i>n</i> = 8), followed by bilateral enucleation and histological assessment. The animals showed good tolerance to the nanoformulation. Maximum IOP values on the right eye occurred shortly after glaucoma induction (T = 62.6 ± 8.3 mmHg; C = 63.6 ± 7.9 mmHg). Animals from the treated group presented a tendency for faster recovery of retinal electrical activity (<i>p</i> > 0.05). EPOβ was detected on the retina of all treated eyes using immunofluorescence. Control animals presented with thinner retinas compared to the treated ones (<i>p</i> < 0.05). Therefore, topical ocular administration of CS/HA-EPOβ nanoparticles enabled EPOβ delivery to the retina of glaucomatous rats and promoted an earlier retinal recovery, confirming EPOβ’s neuroprotective effects. The encouraging results of this preclinical study pave the way for new strategies for topical ocular administration of neuroprotective compounds.
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spelling doaj.art-1f19d5ac502349b7b26e71274b08f0cd2023-11-16T22:35:54ZengMDPI AGPharmaceuticals1424-82472023-01-0116216410.3390/ph16020164Topical Administration of a Nanoformulation of Chitosan-Hyaluronic Acid-Epoetin Beta in a Rat Model of GlaucomaBeatriz Silva0Lídia M. Gonçalves1Berta São Braz2Esmeralda Delgado3CIISA—Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, Universidade de Lisboa Avenida da Universidade Técnica, 1300-477 Lisbon, PortugalResearch Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, PortugalCIISA—Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, Universidade de Lisboa Avenida da Universidade Técnica, 1300-477 Lisbon, PortugalCIISA—Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, Universidade de Lisboa Avenida da Universidade Técnica, 1300-477 Lisbon, PortugalThe present work investigates the effects of chitosan-hyaluronic acid-epoetin beta (CS/HA-EPOβ) nanoparticles after topical ocular administration in a rat glaucoma model. Wistar Hannover rats (<i>n</i> = 24) were submitted to a complete ophthalmological examination and electroretinography, followed by glaucoma induction in their right eye on day 1 of the study. Treatment group (T) received CS/HA-EPOβ nanocarriers (<i>n</i> = 12), while the control group (C) received only empty ones. Electroretinography was repeated on day 3 (<i>n</i> = 24) and before euthanasia on day 7 (<i>n</i> = 8), 14 (<i>n</i> = 8), and 21 (<i>n</i> = 8), followed by bilateral enucleation and histological assessment. The animals showed good tolerance to the nanoformulation. Maximum IOP values on the right eye occurred shortly after glaucoma induction (T = 62.6 ± 8.3 mmHg; C = 63.6 ± 7.9 mmHg). Animals from the treated group presented a tendency for faster recovery of retinal electrical activity (<i>p</i> > 0.05). EPOβ was detected on the retina of all treated eyes using immunofluorescence. Control animals presented with thinner retinas compared to the treated ones (<i>p</i> < 0.05). Therefore, topical ocular administration of CS/HA-EPOβ nanoparticles enabled EPOβ delivery to the retina of glaucomatous rats and promoted an earlier retinal recovery, confirming EPOβ’s neuroprotective effects. The encouraging results of this preclinical study pave the way for new strategies for topical ocular administration of neuroprotective compounds.https://www.mdpi.com/1424-8247/16/2/164glaucomaneuroprotectionnanoparticlesepoetin betachitosanhyaluronic acid
spellingShingle Beatriz Silva
Lídia M. Gonçalves
Berta São Braz
Esmeralda Delgado
Topical Administration of a Nanoformulation of Chitosan-Hyaluronic Acid-Epoetin Beta in a Rat Model of Glaucoma
Pharmaceuticals
glaucoma
neuroprotection
nanoparticles
epoetin beta
chitosan
hyaluronic acid
title Topical Administration of a Nanoformulation of Chitosan-Hyaluronic Acid-Epoetin Beta in a Rat Model of Glaucoma
title_full Topical Administration of a Nanoformulation of Chitosan-Hyaluronic Acid-Epoetin Beta in a Rat Model of Glaucoma
title_fullStr Topical Administration of a Nanoformulation of Chitosan-Hyaluronic Acid-Epoetin Beta in a Rat Model of Glaucoma
title_full_unstemmed Topical Administration of a Nanoformulation of Chitosan-Hyaluronic Acid-Epoetin Beta in a Rat Model of Glaucoma
title_short Topical Administration of a Nanoformulation of Chitosan-Hyaluronic Acid-Epoetin Beta in a Rat Model of Glaucoma
title_sort topical administration of a nanoformulation of chitosan hyaluronic acid epoetin beta in a rat model of glaucoma
topic glaucoma
neuroprotection
nanoparticles
epoetin beta
chitosan
hyaluronic acid
url https://www.mdpi.com/1424-8247/16/2/164
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AT bertasaobraz topicaladministrationofananoformulationofchitosanhyaluronicacidepoetinbetainaratmodelofglaucoma
AT esmeraldadelgado topicaladministrationofananoformulationofchitosanhyaluronicacidepoetinbetainaratmodelofglaucoma