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Ocular Co-Delivery of Timolol and Brimonidine from a Self-Assembling Peptide Hydrogel for the Treatment of Glaucoma: In Vitro and Ex Vivo Evaluation

Effective pharmacotherapy during glaucoma treatment depends on interventions that reduce intraocular pressure (IOP) and retain the IOP lowering effect for sufficient time so as to reduce dosing frequency and enhance patient adherence. Combination anti-glaucoma therapy and dosage forms that increase...

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Autores principales: Taka, Elissavet, Karavasili, Christina, Bouropoulos, Nikolaos, Moschakis, Thomas, Andreadis, Dimitrios D., Zacharis, Constantinos K., Fatouros, Dimitrios G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344471/
https://www.ncbi.nlm.nih.gov/pubmed/32575910
http://dx.doi.org/10.3390/ph13060126
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author Taka, Elissavet
Karavasili, Christina
Bouropoulos, Nikolaos
Moschakis, Thomas
Andreadis, Dimitrios D.
Zacharis, Constantinos K.
Fatouros, Dimitrios G.
author_facet Taka, Elissavet
Karavasili, Christina
Bouropoulos, Nikolaos
Moschakis, Thomas
Andreadis, Dimitrios D.
Zacharis, Constantinos K.
Fatouros, Dimitrios G.
author_sort Taka, Elissavet
collection PubMed
description Effective pharmacotherapy during glaucoma treatment depends on interventions that reduce intraocular pressure (IOP) and retain the IOP lowering effect for sufficient time so as to reduce dosing frequency and enhance patient adherence. Combination anti-glaucoma therapy and dosage forms that increase precorneal residence time could therefore constitute a promising therapeutic intervention. The in-situ gel forming self-assembling peptide ac-(RADA)(4)-CONH(2) was evaluated as carrier for the ocular co-delivery of timolol maleate (TM) and brimonidine tartrate (BR). The hydrogel’s microstructure and mechanical properties were assessed with atomic force microscopy and rheology, respectively. Drug diffusion from the hydrogel was evaluated in vitro in simulated tear fluid and ex vivo across porcine corneas and its effect on the treated corneas was assessed through physicochemical characterization and histological analysis. Results indicated that TM and BR co-delivery affected hydrogel’s microstructure resulting in shorter nanofibers and a less rigid hydrogel matrix. Rapid and complete release of both drugs was achieved within 8 h, while a 2.8-fold and 5.4-fold higher corneal permeability was achieved for TM and BR, respectively. No significant alterations were induced in the structural integrity of the corneas treated with the hydrogel formulation, suggesting that self-assembling peptide hydrogels might serve as promising systems for combination anti-glaucoma therapy.
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spelling pubmed-73444712020-07-14 Ocular Co-Delivery of Timolol and Brimonidine from a Self-Assembling Peptide Hydrogel for the Treatment of Glaucoma: In Vitro and Ex Vivo Evaluation Taka, Elissavet Karavasili, Christina Bouropoulos, Nikolaos Moschakis, Thomas Andreadis, Dimitrios D. Zacharis, Constantinos K. Fatouros, Dimitrios G. Pharmaceuticals (Basel) Article Effective pharmacotherapy during glaucoma treatment depends on interventions that reduce intraocular pressure (IOP) and retain the IOP lowering effect for sufficient time so as to reduce dosing frequency and enhance patient adherence. Combination anti-glaucoma therapy and dosage forms that increase precorneal residence time could therefore constitute a promising therapeutic intervention. The in-situ gel forming self-assembling peptide ac-(RADA)(4)-CONH(2) was evaluated as carrier for the ocular co-delivery of timolol maleate (TM) and brimonidine tartrate (BR). The hydrogel’s microstructure and mechanical properties were assessed with atomic force microscopy and rheology, respectively. Drug diffusion from the hydrogel was evaluated in vitro in simulated tear fluid and ex vivo across porcine corneas and its effect on the treated corneas was assessed through physicochemical characterization and histological analysis. Results indicated that TM and BR co-delivery affected hydrogel’s microstructure resulting in shorter nanofibers and a less rigid hydrogel matrix. Rapid and complete release of both drugs was achieved within 8 h, while a 2.8-fold and 5.4-fold higher corneal permeability was achieved for TM and BR, respectively. No significant alterations were induced in the structural integrity of the corneas treated with the hydrogel formulation, suggesting that self-assembling peptide hydrogels might serve as promising systems for combination anti-glaucoma therapy. MDPI 2020-06-21 /pmc/articles/PMC7344471/ /pubmed/32575910 http://dx.doi.org/10.3390/ph13060126 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Taka, Elissavet
Karavasili, Christina
Bouropoulos, Nikolaos
Moschakis, Thomas
Andreadis, Dimitrios D.
Zacharis, Constantinos K.
Fatouros, Dimitrios G.
Ocular Co-Delivery of Timolol and Brimonidine from a Self-Assembling Peptide Hydrogel for the Treatment of Glaucoma: In Vitro and Ex Vivo Evaluation
title Ocular Co-Delivery of Timolol and Brimonidine from a Self-Assembling Peptide Hydrogel for the Treatment of Glaucoma: In Vitro and Ex Vivo Evaluation
title_full Ocular Co-Delivery of Timolol and Brimonidine from a Self-Assembling Peptide Hydrogel for the Treatment of Glaucoma: In Vitro and Ex Vivo Evaluation
title_fullStr Ocular Co-Delivery of Timolol and Brimonidine from a Self-Assembling Peptide Hydrogel for the Treatment of Glaucoma: In Vitro and Ex Vivo Evaluation
title_full_unstemmed Ocular Co-Delivery of Timolol and Brimonidine from a Self-Assembling Peptide Hydrogel for the Treatment of Glaucoma: In Vitro and Ex Vivo Evaluation
title_short Ocular Co-Delivery of Timolol and Brimonidine from a Self-Assembling Peptide Hydrogel for the Treatment of Glaucoma: In Vitro and Ex Vivo Evaluation
title_sort ocular co-delivery of timolol and brimonidine from a self-assembling peptide hydrogel for the treatment of glaucoma: in vitro and ex vivo evaluation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344471/
https://www.ncbi.nlm.nih.gov/pubmed/32575910
http://dx.doi.org/10.3390/ph13060126
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