Cargando…
Ocular Inserts for Sustained Release of the Angiotensin-Converting Enzyme 2 Activator, Diminazene Aceturate, to Treat Glaucoma in Rats
The aim of this study was to develop and evaluate the effects of chitosan inserts for sustained release of the angiotensin-converting enzyme 2 (ACE2) activator, diminazene aceturate (DIZE), in experimental glaucoma. Monolayer DIZE loaded inserts (D+I) were prepared and characterized through swelling...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4512709/ https://www.ncbi.nlm.nih.gov/pubmed/26204514 http://dx.doi.org/10.1371/journal.pone.0133149 |
_version_ | 1782382549304082432 |
---|---|
author | Foureaux, Giselle Franca, Juçara Ribeiro Nogueira, José Carlos Fulgêncio, Gustavo de Oliveira Ribeiro, Tatiana Gomes Castilho, Rachel Oliveira Yoshida, Maria Irene Fuscaldi, Leonardo Lima Fernandes, Simone Odília Antunes Cardoso, Valbert Nascimento Cronemberger, Sebastião Faraco, André Augusto Gomes Ferreira, Anderson José |
author_facet | Foureaux, Giselle Franca, Juçara Ribeiro Nogueira, José Carlos Fulgêncio, Gustavo de Oliveira Ribeiro, Tatiana Gomes Castilho, Rachel Oliveira Yoshida, Maria Irene Fuscaldi, Leonardo Lima Fernandes, Simone Odília Antunes Cardoso, Valbert Nascimento Cronemberger, Sebastião Faraco, André Augusto Gomes Ferreira, Anderson José |
author_sort | Foureaux, Giselle |
collection | PubMed |
description | The aim of this study was to develop and evaluate the effects of chitosan inserts for sustained release of the angiotensin-converting enzyme 2 (ACE2) activator, diminazene aceturate (DIZE), in experimental glaucoma. Monolayer DIZE loaded inserts (D+I) were prepared and characterized through swelling, attenuated total reflectance Fourier transformed infrared spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC) and in vitro drug release. Functionally, the effects of D+I were tested in glaucomatous rats. Glaucoma was induced by weekly injections of hyaluronic acid (HA) into the anterior chamber and intraocular pressure (IOP) measurements were performed. Retinal ganglion cells (RGC) and optic nerve head cupping were evaluated in histological sections. Biodistribution of the drug was accessed by scintigraphic images and ex vivo radiation counting. We found that DIZE increased the swelling index of the inserts. Also, it was molecularly dispersed and interspersed in the polymeric matrix as a freebase. DIZE did not lose its chemical integrity and activity when loaded in the inserts. The functional evaluation demonstrated that D+I decreased the IOP and maintained the IOP lowered for up to one month (last week: 11.0±0.7 mmHg). This effect of D+I prevented the loss of RGC and degeneration of the optic nerve. No toxic effects in the eyes related to application of the inserts were observed. Moreover, biodistribution studies showed that D+I prolonged the retention of DIZE in the corneal site. We concluded that D+I provided sustained DIZE delivery in vivo, thereby evidencing the potential application of polymeric-based DIZE inserts for glaucoma management. |
format | Online Article Text |
id | pubmed-4512709 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-45127092015-07-24 Ocular Inserts for Sustained Release of the Angiotensin-Converting Enzyme 2 Activator, Diminazene Aceturate, to Treat Glaucoma in Rats Foureaux, Giselle Franca, Juçara Ribeiro Nogueira, José Carlos Fulgêncio, Gustavo de Oliveira Ribeiro, Tatiana Gomes Castilho, Rachel Oliveira Yoshida, Maria Irene Fuscaldi, Leonardo Lima Fernandes, Simone Odília Antunes Cardoso, Valbert Nascimento Cronemberger, Sebastião Faraco, André Augusto Gomes Ferreira, Anderson José PLoS One Research Article The aim of this study was to develop and evaluate the effects of chitosan inserts for sustained release of the angiotensin-converting enzyme 2 (ACE2) activator, diminazene aceturate (DIZE), in experimental glaucoma. Monolayer DIZE loaded inserts (D+I) were prepared and characterized through swelling, attenuated total reflectance Fourier transformed infrared spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC) and in vitro drug release. Functionally, the effects of D+I were tested in glaucomatous rats. Glaucoma was induced by weekly injections of hyaluronic acid (HA) into the anterior chamber and intraocular pressure (IOP) measurements were performed. Retinal ganglion cells (RGC) and optic nerve head cupping were evaluated in histological sections. Biodistribution of the drug was accessed by scintigraphic images and ex vivo radiation counting. We found that DIZE increased the swelling index of the inserts. Also, it was molecularly dispersed and interspersed in the polymeric matrix as a freebase. DIZE did not lose its chemical integrity and activity when loaded in the inserts. The functional evaluation demonstrated that D+I decreased the IOP and maintained the IOP lowered for up to one month (last week: 11.0±0.7 mmHg). This effect of D+I prevented the loss of RGC and degeneration of the optic nerve. No toxic effects in the eyes related to application of the inserts were observed. Moreover, biodistribution studies showed that D+I prolonged the retention of DIZE in the corneal site. We concluded that D+I provided sustained DIZE delivery in vivo, thereby evidencing the potential application of polymeric-based DIZE inserts for glaucoma management. Public Library of Science 2015-07-23 /pmc/articles/PMC4512709/ /pubmed/26204514 http://dx.doi.org/10.1371/journal.pone.0133149 Text en © 2015 Foureaux et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Foureaux, Giselle Franca, Juçara Ribeiro Nogueira, José Carlos Fulgêncio, Gustavo de Oliveira Ribeiro, Tatiana Gomes Castilho, Rachel Oliveira Yoshida, Maria Irene Fuscaldi, Leonardo Lima Fernandes, Simone Odília Antunes Cardoso, Valbert Nascimento Cronemberger, Sebastião Faraco, André Augusto Gomes Ferreira, Anderson José Ocular Inserts for Sustained Release of the Angiotensin-Converting Enzyme 2 Activator, Diminazene Aceturate, to Treat Glaucoma in Rats |
title | Ocular Inserts for Sustained Release of the Angiotensin-Converting Enzyme 2 Activator, Diminazene Aceturate, to Treat Glaucoma in Rats |
title_full | Ocular Inserts for Sustained Release of the Angiotensin-Converting Enzyme 2 Activator, Diminazene Aceturate, to Treat Glaucoma in Rats |
title_fullStr | Ocular Inserts for Sustained Release of the Angiotensin-Converting Enzyme 2 Activator, Diminazene Aceturate, to Treat Glaucoma in Rats |
title_full_unstemmed | Ocular Inserts for Sustained Release of the Angiotensin-Converting Enzyme 2 Activator, Diminazene Aceturate, to Treat Glaucoma in Rats |
title_short | Ocular Inserts for Sustained Release of the Angiotensin-Converting Enzyme 2 Activator, Diminazene Aceturate, to Treat Glaucoma in Rats |
title_sort | ocular inserts for sustained release of the angiotensin-converting enzyme 2 activator, diminazene aceturate, to treat glaucoma in rats |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4512709/ https://www.ncbi.nlm.nih.gov/pubmed/26204514 http://dx.doi.org/10.1371/journal.pone.0133149 |
work_keys_str_mv | AT foureauxgiselle ocularinsertsforsustainedreleaseoftheangiotensinconvertingenzyme2activatordiminazeneaceturatetotreatglaucomainrats AT francajucararibeiro ocularinsertsforsustainedreleaseoftheangiotensinconvertingenzyme2activatordiminazeneaceturatetotreatglaucomainrats AT nogueirajosecarlos ocularinsertsforsustainedreleaseoftheangiotensinconvertingenzyme2activatordiminazeneaceturatetotreatglaucomainrats AT fulgenciogustavodeoliveira ocularinsertsforsustainedreleaseoftheangiotensinconvertingenzyme2activatordiminazeneaceturatetotreatglaucomainrats AT ribeirotatianagomes ocularinsertsforsustainedreleaseoftheangiotensinconvertingenzyme2activatordiminazeneaceturatetotreatglaucomainrats AT castilhoracheloliveira ocularinsertsforsustainedreleaseoftheangiotensinconvertingenzyme2activatordiminazeneaceturatetotreatglaucomainrats AT yoshidamariairene ocularinsertsforsustainedreleaseoftheangiotensinconvertingenzyme2activatordiminazeneaceturatetotreatglaucomainrats AT fuscaldileonardolima ocularinsertsforsustainedreleaseoftheangiotensinconvertingenzyme2activatordiminazeneaceturatetotreatglaucomainrats AT fernandessimoneodiliaantunes ocularinsertsforsustainedreleaseoftheangiotensinconvertingenzyme2activatordiminazeneaceturatetotreatglaucomainrats AT cardosovalbertnascimento ocularinsertsforsustainedreleaseoftheangiotensinconvertingenzyme2activatordiminazeneaceturatetotreatglaucomainrats AT cronembergersebastiao ocularinsertsforsustainedreleaseoftheangiotensinconvertingenzyme2activatordiminazeneaceturatetotreatglaucomainrats AT faracoandreaugustogomes ocularinsertsforsustainedreleaseoftheangiotensinconvertingenzyme2activatordiminazeneaceturatetotreatglaucomainrats AT ferreiraandersonjose ocularinsertsforsustainedreleaseoftheangiotensinconvertingenzyme2activatordiminazeneaceturatetotreatglaucomainrats |