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New In Vitro Methodology for Kinetics Distribution Prediction in the Brain. An Additional Step towards an Animal-Free Approach
SIMPLE SUMMARY: The prevalence of neurological disorders in humans is rising year after year. This fact necessitates the development of new drugs for treating these pathologies. Traditionally, drugs have been tested in animals prior to use in human experiments; however, the use of animals in experim...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8697921/ https://www.ncbi.nlm.nih.gov/pubmed/34944295 http://dx.doi.org/10.3390/ani11123521 |
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author | Sánchez-Dengra, Bárbara González-Álvarez, Isabel González-Álvarez, Marta Bermejo, Marival |
author_facet | Sánchez-Dengra, Bárbara González-Álvarez, Isabel González-Álvarez, Marta Bermejo, Marival |
author_sort | Sánchez-Dengra, Bárbara |
collection | PubMed |
description | SIMPLE SUMMARY: The prevalence of neurological disorders in humans is rising year after year. This fact necessitates the development of new drugs for treating these pathologies. Traditionally, drugs have been tested in animals prior to use in human experiments; however, the use of animals in experimentation must be controlled and as low as possible. Because of that, here we proposed a new in vitro approach with which the access and distribution of drugs into the brain can be evaluated without using/killing any animals. ABSTRACT: The development of new drugs or formulations for central nervous system (CNS) diseases is a complex pharmacologic and pharmacokinetic process; it is important to evaluate their access to the CNS through the blood–brain barrier (BBB) and their distribution once they have acceded to the brain. The gold standard tool for obtaining this information is the animal microdialysis technique; however, according to 3Rs principles, it would be better to have an “animal-free” alternative technique. Because of that, the purpose of this work was to develop a new formulation to substitute the brain homogenate in the in vitro tests used for the prediction of a drug’s distribution in the brain. Fresh eggs have been used to prepare an emulsion with the same proportion in proteins and lipids as a human brain; this emulsion has proved to be able to predict both the unbound fraction of drug in the brain (f(u,brain)) and the apparent volume of distribution in the brain (V(u,brain)) when tested in in vitro permeability tests. The new formulation could be used as a screening tool; only the drugs with a proper in vitro distribution would pass to microdialysis studies, contributing to the refinement, reduction and replacement of animals in research. |
format | Online Article Text |
id | pubmed-8697921 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86979212021-12-24 New In Vitro Methodology for Kinetics Distribution Prediction in the Brain. An Additional Step towards an Animal-Free Approach Sánchez-Dengra, Bárbara González-Álvarez, Isabel González-Álvarez, Marta Bermejo, Marival Animals (Basel) Article SIMPLE SUMMARY: The prevalence of neurological disorders in humans is rising year after year. This fact necessitates the development of new drugs for treating these pathologies. Traditionally, drugs have been tested in animals prior to use in human experiments; however, the use of animals in experimentation must be controlled and as low as possible. Because of that, here we proposed a new in vitro approach with which the access and distribution of drugs into the brain can be evaluated without using/killing any animals. ABSTRACT: The development of new drugs or formulations for central nervous system (CNS) diseases is a complex pharmacologic and pharmacokinetic process; it is important to evaluate their access to the CNS through the blood–brain barrier (BBB) and their distribution once they have acceded to the brain. The gold standard tool for obtaining this information is the animal microdialysis technique; however, according to 3Rs principles, it would be better to have an “animal-free” alternative technique. Because of that, the purpose of this work was to develop a new formulation to substitute the brain homogenate in the in vitro tests used for the prediction of a drug’s distribution in the brain. Fresh eggs have been used to prepare an emulsion with the same proportion in proteins and lipids as a human brain; this emulsion has proved to be able to predict both the unbound fraction of drug in the brain (f(u,brain)) and the apparent volume of distribution in the brain (V(u,brain)) when tested in in vitro permeability tests. The new formulation could be used as a screening tool; only the drugs with a proper in vitro distribution would pass to microdialysis studies, contributing to the refinement, reduction and replacement of animals in research. MDPI 2021-12-10 /pmc/articles/PMC8697921/ /pubmed/34944295 http://dx.doi.org/10.3390/ani11123521 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 Sánchez-Dengra, Bárbara González-Álvarez, Isabel González-Álvarez, Marta Bermejo, Marival New In Vitro Methodology for Kinetics Distribution Prediction in the Brain. An Additional Step towards an Animal-Free Approach |
title | New In Vitro Methodology for Kinetics Distribution Prediction in the Brain. An Additional Step towards an Animal-Free Approach |
title_full | New In Vitro Methodology for Kinetics Distribution Prediction in the Brain. An Additional Step towards an Animal-Free Approach |
title_fullStr | New In Vitro Methodology for Kinetics Distribution Prediction in the Brain. An Additional Step towards an Animal-Free Approach |
title_full_unstemmed | New In Vitro Methodology for Kinetics Distribution Prediction in the Brain. An Additional Step towards an Animal-Free Approach |
title_short | New In Vitro Methodology for Kinetics Distribution Prediction in the Brain. An Additional Step towards an Animal-Free Approach |
title_sort | new in vitro methodology for kinetics distribution prediction in the brain. an additional step towards an animal-free approach |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8697921/ https://www.ncbi.nlm.nih.gov/pubmed/34944295 http://dx.doi.org/10.3390/ani11123521 |
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