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Non-toxic polymer nanovectors for improved delivery of dexamethasone

Dexamethasone (Dex) is a highly insoluble front-line drug used in cancer therapy. Data from clinical trials indicates that the pharmacokinetics of Dex vary considerably between patients and prolonging drug exposure rather than increasing absolute dose may improve efficacy. Non-toxic, fully biodegrad...

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Autores principales: Ede, Benjamin C., Diamanti, Paraskevi, Williams, David S., Blair, Allison
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390661/
https://www.ncbi.nlm.nih.gov/pubmed/34446801
http://dx.doi.org/10.1038/s41598-021-96797-4
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author Ede, Benjamin C.
Diamanti, Paraskevi
Williams, David S.
Blair, Allison
author_facet Ede, Benjamin C.
Diamanti, Paraskevi
Williams, David S.
Blair, Allison
author_sort Ede, Benjamin C.
collection PubMed
description Dexamethasone (Dex) is a highly insoluble front-line drug used in cancer therapy. Data from clinical trials indicates that the pharmacokinetics of Dex vary considerably between patients and prolonging drug exposure rather than increasing absolute dose may improve efficacy. Non-toxic, fully biodegradable Dex loaded nanovectors (NV) were formulated, via simple direct hydration within 10 min, as a vehicle to extend exposure and distribution in vivo. Dex-NV were just as effective as the free drug against primary human leukemia cells in vitro and in vivo. Importantly, high levels of DMSO solvent were not required in the NV formulations. Broad distribution of NV was seen rapidly following inoculation into mice. NV accumulated in major organs, including bone marrow and brain, known sanctuary sites for ALL. The study describes a non-toxic, more easily scalable system for improving Dex solubility for use in cancer and can be applied to other medical conditions associated with inflammation.
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spelling pubmed-83906612021-09-01 Non-toxic polymer nanovectors for improved delivery of dexamethasone Ede, Benjamin C. Diamanti, Paraskevi Williams, David S. Blair, Allison Sci Rep Article Dexamethasone (Dex) is a highly insoluble front-line drug used in cancer therapy. Data from clinical trials indicates that the pharmacokinetics of Dex vary considerably between patients and prolonging drug exposure rather than increasing absolute dose may improve efficacy. Non-toxic, fully biodegradable Dex loaded nanovectors (NV) were formulated, via simple direct hydration within 10 min, as a vehicle to extend exposure and distribution in vivo. Dex-NV were just as effective as the free drug against primary human leukemia cells in vitro and in vivo. Importantly, high levels of DMSO solvent were not required in the NV formulations. Broad distribution of NV was seen rapidly following inoculation into mice. NV accumulated in major organs, including bone marrow and brain, known sanctuary sites for ALL. The study describes a non-toxic, more easily scalable system for improving Dex solubility for use in cancer and can be applied to other medical conditions associated with inflammation. Nature Publishing Group UK 2021-08-26 /pmc/articles/PMC8390661/ /pubmed/34446801 http://dx.doi.org/10.1038/s41598-021-96797-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ede, Benjamin C.
Diamanti, Paraskevi
Williams, David S.
Blair, Allison
Non-toxic polymer nanovectors for improved delivery of dexamethasone
title Non-toxic polymer nanovectors for improved delivery of dexamethasone
title_full Non-toxic polymer nanovectors for improved delivery of dexamethasone
title_fullStr Non-toxic polymer nanovectors for improved delivery of dexamethasone
title_full_unstemmed Non-toxic polymer nanovectors for improved delivery of dexamethasone
title_short Non-toxic polymer nanovectors for improved delivery of dexamethasone
title_sort non-toxic polymer nanovectors for improved delivery of dexamethasone
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390661/
https://www.ncbi.nlm.nih.gov/pubmed/34446801
http://dx.doi.org/10.1038/s41598-021-96797-4
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