Bimatoprost-loaded ocular inserts as sustained release drug delivery systems for glaucoma treatment: in vitro and in vivo evaluation.
The purpose of the present study was to develop and assess a novel sustained-release drug delivery system of Bimatoprost (BIM). Chitosan polymeric inserts were prepared using the solvent casting method and characterized by swelling studies, infrared spectroscopy, differential scanning calorimetry, d...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4005758?pdf=render |
| _version_ | 1819327321430032384 |
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| author | Juçara Ribeiro Franca Giselle Foureaux Leonardo Lima Fuscaldi Tatiana Gomes Ribeiro Lívia Bomfim Rodrigues Renata Bravo Rachel Oliveira Castilho Maria Irene Yoshida Valbert Nascimento Cardoso Simone Odília Fernandes Sebastião Cronemberger Anderson José Ferreira André Augusto Gomes Faraco |
| author_facet | Juçara Ribeiro Franca Giselle Foureaux Leonardo Lima Fuscaldi Tatiana Gomes Ribeiro Lívia Bomfim Rodrigues Renata Bravo Rachel Oliveira Castilho Maria Irene Yoshida Valbert Nascimento Cardoso Simone Odília Fernandes Sebastião Cronemberger Anderson José Ferreira André Augusto Gomes Faraco |
| author_sort | Juçara Ribeiro Franca |
| collection | DOAJ |
| description | The purpose of the present study was to develop and assess a novel sustained-release drug delivery system of Bimatoprost (BIM). Chitosan polymeric inserts were prepared using the solvent casting method and characterized by swelling studies, infrared spectroscopy, differential scanning calorimetry, drug content, scanning electron microscopy and in vitro drug release. Biodistribution of 99mTc-BIM eye drops and 99mTc-BIM-loaded inserts, after ocular administration in Wistar rats, was accessed by ex vivo radiation counting. The inserts were evaluated for their therapeutic efficacy in glaucomatous Wistar rats. Glaucoma was induced by weekly intracameral injection of hyaluronic acid. BIM-loaded inserts (equivalent to 9.0 µg BIM) were administered once into conjunctival sac, after ocular hypertension confirmation. BIM eye drop was topically instilled in a second group of glaucomatous rats for 15 days days, while placebo inserts were administered once in a third group. An untreated glaucomatous group was used as control. Intraocular pressure (IOP) was monitored for four consecutive weeks after treatment began. At the end of the experiment, retinal ganglion cells and optic nerve head cupping were evaluated in the histological eye sections. Characterization results revealed that the drug physically interacted, but did not chemically react with the polymeric matrix. Inserts sustainedly released BIM in vitro during 8 hours. Biodistribution studies showed that the amount of 99mTc-BIM that remained in the eye was significantly lower after eye drop instillation than after chitosan insert implantation. BIM-loaded inserts lowered IOP for 4 weeks, after one application, while IOP values remained significantly high for the placebo and untreated groups. Eye drops were only effective during the daily treatment period. IOP results were reflected in RGC counting and optic nerve head cupping damage. BIM-loaded inserts provided sustained release of BIM and seem to be a promising system for glaucoma management. |
| first_indexed | 2024-12-24T13:08:59Z |
| format | Article |
| id | doaj.art-39e25685b2524a57ba662d9214c0c86c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-24T13:08:59Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-39e25685b2524a57ba662d9214c0c86c2022-12-21T16:53:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9546110.1371/journal.pone.0095461Bimatoprost-loaded ocular inserts as sustained release drug delivery systems for glaucoma treatment: in vitro and in vivo evaluation.Juçara Ribeiro FrancaGiselle FoureauxLeonardo Lima FuscaldiTatiana Gomes RibeiroLívia Bomfim RodriguesRenata BravoRachel Oliveira CastilhoMaria Irene YoshidaValbert Nascimento CardosoSimone Odília FernandesSebastião CronembergerAnderson José FerreiraAndré Augusto Gomes FaracoThe purpose of the present study was to develop and assess a novel sustained-release drug delivery system of Bimatoprost (BIM). Chitosan polymeric inserts were prepared using the solvent casting method and characterized by swelling studies, infrared spectroscopy, differential scanning calorimetry, drug content, scanning electron microscopy and in vitro drug release. Biodistribution of 99mTc-BIM eye drops and 99mTc-BIM-loaded inserts, after ocular administration in Wistar rats, was accessed by ex vivo radiation counting. The inserts were evaluated for their therapeutic efficacy in glaucomatous Wistar rats. Glaucoma was induced by weekly intracameral injection of hyaluronic acid. BIM-loaded inserts (equivalent to 9.0 µg BIM) were administered once into conjunctival sac, after ocular hypertension confirmation. BIM eye drop was topically instilled in a second group of glaucomatous rats for 15 days days, while placebo inserts were administered once in a third group. An untreated glaucomatous group was used as control. Intraocular pressure (IOP) was monitored for four consecutive weeks after treatment began. At the end of the experiment, retinal ganglion cells and optic nerve head cupping were evaluated in the histological eye sections. Characterization results revealed that the drug physically interacted, but did not chemically react with the polymeric matrix. Inserts sustainedly released BIM in vitro during 8 hours. Biodistribution studies showed that the amount of 99mTc-BIM that remained in the eye was significantly lower after eye drop instillation than after chitosan insert implantation. BIM-loaded inserts lowered IOP for 4 weeks, after one application, while IOP values remained significantly high for the placebo and untreated groups. Eye drops were only effective during the daily treatment period. IOP results were reflected in RGC counting and optic nerve head cupping damage. BIM-loaded inserts provided sustained release of BIM and seem to be a promising system for glaucoma management.http://europepmc.org/articles/PMC4005758?pdf=render |
| spellingShingle | Juçara Ribeiro Franca Giselle Foureaux Leonardo Lima Fuscaldi Tatiana Gomes Ribeiro Lívia Bomfim Rodrigues Renata Bravo Rachel Oliveira Castilho Maria Irene Yoshida Valbert Nascimento Cardoso Simone Odília Fernandes Sebastião Cronemberger Anderson José Ferreira André Augusto Gomes Faraco Bimatoprost-loaded ocular inserts as sustained release drug delivery systems for glaucoma treatment: in vitro and in vivo evaluation. PLoS ONE |
| title | Bimatoprost-loaded ocular inserts as sustained release drug delivery systems for glaucoma treatment: in vitro and in vivo evaluation. |
| title_full | Bimatoprost-loaded ocular inserts as sustained release drug delivery systems for glaucoma treatment: in vitro and in vivo evaluation. |
| title_fullStr | Bimatoprost-loaded ocular inserts as sustained release drug delivery systems for glaucoma treatment: in vitro and in vivo evaluation. |
| title_full_unstemmed | Bimatoprost-loaded ocular inserts as sustained release drug delivery systems for glaucoma treatment: in vitro and in vivo evaluation. |
| title_short | Bimatoprost-loaded ocular inserts as sustained release drug delivery systems for glaucoma treatment: in vitro and in vivo evaluation. |
| title_sort | bimatoprost loaded ocular inserts as sustained release drug delivery systems for glaucoma treatment in vitro and in vivo evaluation |
| url | http://europepmc.org/articles/PMC4005758?pdf=render |
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