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Mitigation of Tacrolimus-Associated Nephrotoxicity by PLGA Nanoparticulate Delivery Following Multiple Dosing to Mice while Maintaining its Immunosuppressive Activity

The aim of this study was to assess the ability of PLGA nanoparticles (NPs) to reduce the tacrolimus (TAC)-associated nephrotoxicity following multiple dose administration. The mean diameter of prepared NPs was in the range of 227 to 263 nm with an 8.32% drug loading (w/w). Moreover, in vitro releas...

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Autores principales: Alshamsan, Aws, Binkhathlan, Ziyad, Kalam, Mohd Abul, Qamar, Wajhul, Kfouri, Hala, Alghonaim, Mohammed, Lavasanifar, Afsaneh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174389/
https://www.ncbi.nlm.nih.gov/pubmed/32317681
http://dx.doi.org/10.1038/s41598-020-63767-1
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author Alshamsan, Aws
Binkhathlan, Ziyad
Kalam, Mohd Abul
Qamar, Wajhul
Kfouri, Hala
Alghonaim, Mohammed
Lavasanifar, Afsaneh
author_facet Alshamsan, Aws
Binkhathlan, Ziyad
Kalam, Mohd Abul
Qamar, Wajhul
Kfouri, Hala
Alghonaim, Mohammed
Lavasanifar, Afsaneh
author_sort Alshamsan, Aws
collection PubMed
description The aim of this study was to assess the ability of PLGA nanoparticles (NPs) to reduce the tacrolimus (TAC)-associated nephrotoxicity following multiple dose administration. The mean diameter of prepared NPs was in the range of 227 to 263 nm with an 8.32% drug loading (w/w). Moreover, in vitro release profile of TAC-loaded NPs showed a sustained release of the drug with only less than 30% release within 12 days. Flow cytometry as well as fluorescence microscopy results confirmed the uptake of FITC-labelled PLGA NPs by dendritic cells. The ex vivo study showed that TAC-loaded NPs caused a significant suppression of the proliferation of CD4(+) and CD8(+) cells, which was comparable to the control formulation (Prograf). In vivo immunosuppressive activity as well as the kidney function were assessed following drug administration to mice. The animals received TAC subcutaneously at a daily dose of 1 mg/kg for 30 days delivered as the control formulation (Prograf) or TAC-loaded NPs. The results revealed significantly lower drug-associated toxicity with an activity comparable to Prograf for TAC-loaded PLGA NPs. These findings show a potential for PLGA NPs in reducing the nephrotoxicity of TAC while preserving the immunosuppressive activity.
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spelling pubmed-71743892020-04-24 Mitigation of Tacrolimus-Associated Nephrotoxicity by PLGA Nanoparticulate Delivery Following Multiple Dosing to Mice while Maintaining its Immunosuppressive Activity Alshamsan, Aws Binkhathlan, Ziyad Kalam, Mohd Abul Qamar, Wajhul Kfouri, Hala Alghonaim, Mohammed Lavasanifar, Afsaneh Sci Rep Article The aim of this study was to assess the ability of PLGA nanoparticles (NPs) to reduce the tacrolimus (TAC)-associated nephrotoxicity following multiple dose administration. The mean diameter of prepared NPs was in the range of 227 to 263 nm with an 8.32% drug loading (w/w). Moreover, in vitro release profile of TAC-loaded NPs showed a sustained release of the drug with only less than 30% release within 12 days. Flow cytometry as well as fluorescence microscopy results confirmed the uptake of FITC-labelled PLGA NPs by dendritic cells. The ex vivo study showed that TAC-loaded NPs caused a significant suppression of the proliferation of CD4(+) and CD8(+) cells, which was comparable to the control formulation (Prograf). In vivo immunosuppressive activity as well as the kidney function were assessed following drug administration to mice. The animals received TAC subcutaneously at a daily dose of 1 mg/kg for 30 days delivered as the control formulation (Prograf) or TAC-loaded NPs. The results revealed significantly lower drug-associated toxicity with an activity comparable to Prograf for TAC-loaded PLGA NPs. These findings show a potential for PLGA NPs in reducing the nephrotoxicity of TAC while preserving the immunosuppressive activity. Nature Publishing Group UK 2020-04-21 /pmc/articles/PMC7174389/ /pubmed/32317681 http://dx.doi.org/10.1038/s41598-020-63767-1 Text en © The Author(s) 2020 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Alshamsan, Aws
Binkhathlan, Ziyad
Kalam, Mohd Abul
Qamar, Wajhul
Kfouri, Hala
Alghonaim, Mohammed
Lavasanifar, Afsaneh
Mitigation of Tacrolimus-Associated Nephrotoxicity by PLGA Nanoparticulate Delivery Following Multiple Dosing to Mice while Maintaining its Immunosuppressive Activity
title Mitigation of Tacrolimus-Associated Nephrotoxicity by PLGA Nanoparticulate Delivery Following Multiple Dosing to Mice while Maintaining its Immunosuppressive Activity
title_full Mitigation of Tacrolimus-Associated Nephrotoxicity by PLGA Nanoparticulate Delivery Following Multiple Dosing to Mice while Maintaining its Immunosuppressive Activity
title_fullStr Mitigation of Tacrolimus-Associated Nephrotoxicity by PLGA Nanoparticulate Delivery Following Multiple Dosing to Mice while Maintaining its Immunosuppressive Activity
title_full_unstemmed Mitigation of Tacrolimus-Associated Nephrotoxicity by PLGA Nanoparticulate Delivery Following Multiple Dosing to Mice while Maintaining its Immunosuppressive Activity
title_short Mitigation of Tacrolimus-Associated Nephrotoxicity by PLGA Nanoparticulate Delivery Following Multiple Dosing to Mice while Maintaining its Immunosuppressive Activity
title_sort mitigation of tacrolimus-associated nephrotoxicity by plga nanoparticulate delivery following multiple dosing to mice while maintaining its immunosuppressive activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174389/
https://www.ncbi.nlm.nih.gov/pubmed/32317681
http://dx.doi.org/10.1038/s41598-020-63767-1
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