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β-Cyclodextrin as a Functional Excipient Used for Enhancing the Diminazene Aceturate Bioavailability
In this study, we proposed formulations of diminazene aceturate (DA) designed to improve its bioavailability and to maximize the therapeutic index in animals by overcoming the rapid degradation under the acidic pH of the stomach. An important consequence is the fact that its amount in the bloodstrea...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630424/ https://www.ncbi.nlm.nih.gov/pubmed/31234525 http://dx.doi.org/10.3390/pharmaceutics11060295 |
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author | Marangoci, Narcisa Timpu, Daniel Corciova, Andreia Mircea, Cornelia Petrovici, Anca-Roxana Nicolescu, Alina Ursu, Elena-Laura Nastasa, Valentin Bostanaru, Andra-Cristina Mares, Mihai Pertea, Mihaela Pinteala, Mariana |
author_facet | Marangoci, Narcisa Timpu, Daniel Corciova, Andreia Mircea, Cornelia Petrovici, Anca-Roxana Nicolescu, Alina Ursu, Elena-Laura Nastasa, Valentin Bostanaru, Andra-Cristina Mares, Mihai Pertea, Mihaela Pinteala, Mariana |
author_sort | Marangoci, Narcisa |
collection | PubMed |
description | In this study, we proposed formulations of diminazene aceturate (DA) designed to improve its bioavailability and to maximize the therapeutic index in animals by overcoming the rapid degradation under the acidic pH of the stomach. An important consequence is the fact that its amount in the bloodstream is close to the administered dose. This was made possible by incorporating DA into the β-cyclodextrin’s (βCD) cavity in a molar ratio of 1:1. The structure of the resulted inclusion complex was established by Raman, DSC, and Wide-Angle X ray Diffraction (WAXD) in solid state and by (1)H-NMR and H-H ROESY in aqueous solutions. The stoichiometry of the DA:βCD inclusion complex was obtained by using the continuous variation method (Job’s plot), considering the chemical shifts variations of protons from both DA and βCD compounds in (1)H-NMR spectra. The biological activity was estimated in vitro by antioxidant activity and in vivo by comparing the bioavailability of parent DA and its inclusion complexes after a single dose administration in Wistar rats by using the HPLC method on their blood plasma. In vitro tests showed an improved antioxidant activity. In vivo tests have shown that the DA concentration is always much higher in blood plasma of rats when DA:βCD inclusion complex of 1:1 molar ratio was administered (i.e., at 60 min, DA is around 11 and 3 times higher when DA:βCD inclusion complex of 1:1 molar ratio was administered than the parent DA one and DA:βCD lyophilized mixture of 1:2 molar ratio, respectively). |
format | Online Article Text |
id | pubmed-6630424 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-66304242019-08-19 β-Cyclodextrin as a Functional Excipient Used for Enhancing the Diminazene Aceturate Bioavailability Marangoci, Narcisa Timpu, Daniel Corciova, Andreia Mircea, Cornelia Petrovici, Anca-Roxana Nicolescu, Alina Ursu, Elena-Laura Nastasa, Valentin Bostanaru, Andra-Cristina Mares, Mihai Pertea, Mihaela Pinteala, Mariana Pharmaceutics Article In this study, we proposed formulations of diminazene aceturate (DA) designed to improve its bioavailability and to maximize the therapeutic index in animals by overcoming the rapid degradation under the acidic pH of the stomach. An important consequence is the fact that its amount in the bloodstream is close to the administered dose. This was made possible by incorporating DA into the β-cyclodextrin’s (βCD) cavity in a molar ratio of 1:1. The structure of the resulted inclusion complex was established by Raman, DSC, and Wide-Angle X ray Diffraction (WAXD) in solid state and by (1)H-NMR and H-H ROESY in aqueous solutions. The stoichiometry of the DA:βCD inclusion complex was obtained by using the continuous variation method (Job’s plot), considering the chemical shifts variations of protons from both DA and βCD compounds in (1)H-NMR spectra. The biological activity was estimated in vitro by antioxidant activity and in vivo by comparing the bioavailability of parent DA and its inclusion complexes after a single dose administration in Wistar rats by using the HPLC method on their blood plasma. In vitro tests showed an improved antioxidant activity. In vivo tests have shown that the DA concentration is always much higher in blood plasma of rats when DA:βCD inclusion complex of 1:1 molar ratio was administered (i.e., at 60 min, DA is around 11 and 3 times higher when DA:βCD inclusion complex of 1:1 molar ratio was administered than the parent DA one and DA:βCD lyophilized mixture of 1:2 molar ratio, respectively). MDPI 2019-06-22 /pmc/articles/PMC6630424/ /pubmed/31234525 http://dx.doi.org/10.3390/pharmaceutics11060295 Text en © 2019 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 Marangoci, Narcisa Timpu, Daniel Corciova, Andreia Mircea, Cornelia Petrovici, Anca-Roxana Nicolescu, Alina Ursu, Elena-Laura Nastasa, Valentin Bostanaru, Andra-Cristina Mares, Mihai Pertea, Mihaela Pinteala, Mariana β-Cyclodextrin as a Functional Excipient Used for Enhancing the Diminazene Aceturate Bioavailability |
title | β-Cyclodextrin as a Functional Excipient Used for Enhancing the Diminazene Aceturate Bioavailability |
title_full | β-Cyclodextrin as a Functional Excipient Used for Enhancing the Diminazene Aceturate Bioavailability |
title_fullStr | β-Cyclodextrin as a Functional Excipient Used for Enhancing the Diminazene Aceturate Bioavailability |
title_full_unstemmed | β-Cyclodextrin as a Functional Excipient Used for Enhancing the Diminazene Aceturate Bioavailability |
title_short | β-Cyclodextrin as a Functional Excipient Used for Enhancing the Diminazene Aceturate Bioavailability |
title_sort | β-cyclodextrin as a functional excipient used for enhancing the diminazene aceturate bioavailability |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630424/ https://www.ncbi.nlm.nih.gov/pubmed/31234525 http://dx.doi.org/10.3390/pharmaceutics11060295 |
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