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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...

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Autores principales: 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
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
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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.
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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
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