Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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
_version_ 1783435299312893952
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
work_keys_str_mv AT marangocinarcisa bcyclodextrinasafunctionalexcipientusedforenhancingthediminazeneaceturatebioavailability
AT timpudaniel bcyclodextrinasafunctionalexcipientusedforenhancingthediminazeneaceturatebioavailability
AT corciovaandreia bcyclodextrinasafunctionalexcipientusedforenhancingthediminazeneaceturatebioavailability
AT mirceacornelia bcyclodextrinasafunctionalexcipientusedforenhancingthediminazeneaceturatebioavailability
AT petroviciancaroxana bcyclodextrinasafunctionalexcipientusedforenhancingthediminazeneaceturatebioavailability
AT nicolescualina bcyclodextrinasafunctionalexcipientusedforenhancingthediminazeneaceturatebioavailability
AT ursuelenalaura bcyclodextrinasafunctionalexcipientusedforenhancingthediminazeneaceturatebioavailability
AT nastasavalentin bcyclodextrinasafunctionalexcipientusedforenhancingthediminazeneaceturatebioavailability
AT bostanaruandracristina bcyclodextrinasafunctionalexcipientusedforenhancingthediminazeneaceturatebioavailability
AT maresmihai bcyclodextrinasafunctionalexcipientusedforenhancingthediminazeneaceturatebioavailability
AT perteamihaela bcyclodextrinasafunctionalexcipientusedforenhancingthediminazeneaceturatebioavailability
AT pintealamariana bcyclodextrinasafunctionalexcipientusedforenhancingthediminazeneaceturatebioavailability