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Pharmacokinetics and Toxicity Evaluation of a PLGA and Chitosan-Based Micro-Implant for Sustained Release of Methotrexate in Rabbit Vitreous

The present research investigates the pharmacokinetics and toxicity of a chitosan (CS) and poly(lactic-co-glycolic) acid (PLGA)-based methotrexate (MTX) intravitreal micro-implant in normal rabbit eyes. PLGA and CS-based micro-implants containing 400 µg of MTX were surgically inserted in the vitreou...

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Autores principales: Manna, Soumyarwit, Donnell, Anna M., Faraj, Rafaela Q. Caixeta, Riemann, Blanca I., Riemann, Christopher D., Augsburger, James J., Correa, Zelia M., Banerjee, Rupak K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398642/
https://www.ncbi.nlm.nih.gov/pubmed/34452188
http://dx.doi.org/10.3390/pharmaceutics13081227
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author Manna, Soumyarwit
Donnell, Anna M.
Faraj, Rafaela Q. Caixeta
Riemann, Blanca I.
Riemann, Christopher D.
Augsburger, James J.
Correa, Zelia M.
Banerjee, Rupak K.
author_facet Manna, Soumyarwit
Donnell, Anna M.
Faraj, Rafaela Q. Caixeta
Riemann, Blanca I.
Riemann, Christopher D.
Augsburger, James J.
Correa, Zelia M.
Banerjee, Rupak K.
author_sort Manna, Soumyarwit
collection PubMed
description The present research investigates the pharmacokinetics and toxicity of a chitosan (CS) and poly(lactic-co-glycolic) acid (PLGA)-based methotrexate (MTX) intravitreal micro-implant in normal rabbit eyes. PLGA and CS-based micro-implants containing 400 µg of MTX were surgically inserted in the vitreous of twenty-four New Zealand rabbits using minimally invasive procedures. The PLGA-coated CS-MTX micro-implant and the placebo micro-implant were inserted in the right eye and in the left eye, respectively, of each rabbit. The intravitreal MTX concentration was evaluated on Days 1, 3, 7, 14, 28 and 56. A therapeutic concentration of MTX (0.1–1.0 µM) in the rabbit vitreous was observed for 56 days. The release of MTX in the therapeutic release phase followed first-order kinetics. Histopathologic evaluation on Days 14, 28 and 56 of the enucleated eyes demonstrated no signs of toxicity or any anatomical irregularity in the vitreoretinal domain. Additionally, the micro-implants were stationary at the position of their implantation throughout the duration of the study. The PLGA-coated CS-MTX micro-implant can serve as a potential alternative to the current treatment modality of intravitreal MTX injections based on its performance, thereby avoiding associated complications and the treatment burden of multiple injections.
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spelling pubmed-83986422021-08-29 Pharmacokinetics and Toxicity Evaluation of a PLGA and Chitosan-Based Micro-Implant for Sustained Release of Methotrexate in Rabbit Vitreous Manna, Soumyarwit Donnell, Anna M. Faraj, Rafaela Q. Caixeta Riemann, Blanca I. Riemann, Christopher D. Augsburger, James J. Correa, Zelia M. Banerjee, Rupak K. Pharmaceutics Article The present research investigates the pharmacokinetics and toxicity of a chitosan (CS) and poly(lactic-co-glycolic) acid (PLGA)-based methotrexate (MTX) intravitreal micro-implant in normal rabbit eyes. PLGA and CS-based micro-implants containing 400 µg of MTX were surgically inserted in the vitreous of twenty-four New Zealand rabbits using minimally invasive procedures. The PLGA-coated CS-MTX micro-implant and the placebo micro-implant were inserted in the right eye and in the left eye, respectively, of each rabbit. The intravitreal MTX concentration was evaluated on Days 1, 3, 7, 14, 28 and 56. A therapeutic concentration of MTX (0.1–1.0 µM) in the rabbit vitreous was observed for 56 days. The release of MTX in the therapeutic release phase followed first-order kinetics. Histopathologic evaluation on Days 14, 28 and 56 of the enucleated eyes demonstrated no signs of toxicity or any anatomical irregularity in the vitreoretinal domain. Additionally, the micro-implants were stationary at the position of their implantation throughout the duration of the study. The PLGA-coated CS-MTX micro-implant can serve as a potential alternative to the current treatment modality of intravitreal MTX injections based on its performance, thereby avoiding associated complications and the treatment burden of multiple injections. MDPI 2021-08-09 /pmc/articles/PMC8398642/ /pubmed/34452188 http://dx.doi.org/10.3390/pharmaceutics13081227 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Manna, Soumyarwit
Donnell, Anna M.
Faraj, Rafaela Q. Caixeta
Riemann, Blanca I.
Riemann, Christopher D.
Augsburger, James J.
Correa, Zelia M.
Banerjee, Rupak K.
Pharmacokinetics and Toxicity Evaluation of a PLGA and Chitosan-Based Micro-Implant for Sustained Release of Methotrexate in Rabbit Vitreous
title Pharmacokinetics and Toxicity Evaluation of a PLGA and Chitosan-Based Micro-Implant for Sustained Release of Methotrexate in Rabbit Vitreous
title_full Pharmacokinetics and Toxicity Evaluation of a PLGA and Chitosan-Based Micro-Implant for Sustained Release of Methotrexate in Rabbit Vitreous
title_fullStr Pharmacokinetics and Toxicity Evaluation of a PLGA and Chitosan-Based Micro-Implant for Sustained Release of Methotrexate in Rabbit Vitreous
title_full_unstemmed Pharmacokinetics and Toxicity Evaluation of a PLGA and Chitosan-Based Micro-Implant for Sustained Release of Methotrexate in Rabbit Vitreous
title_short Pharmacokinetics and Toxicity Evaluation of a PLGA and Chitosan-Based Micro-Implant for Sustained Release of Methotrexate in Rabbit Vitreous
title_sort pharmacokinetics and toxicity evaluation of a plga and chitosan-based micro-implant for sustained release of methotrexate in rabbit vitreous
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398642/
https://www.ncbi.nlm.nih.gov/pubmed/34452188
http://dx.doi.org/10.3390/pharmaceutics13081227
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