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Preparation, characterization, and biodistribution of glutathione PEGylated nanoliposomal doxorubicin for brain drug delivery with a post-insertion approach
OBJECTIVE(S): Brain cancer treatments have mainly failed due to their inability to cross the blood-brain barrier. Several studies have confirmed the presence of glutathione (GSH) receptors on BBB’s surface, as a result, products like 2B3-101, which contain over 5% pre-inserted GSH PEGylated liposoma...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Mashhad University of Medical Sciences
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9148397/ https://www.ncbi.nlm.nih.gov/pubmed/35656188 http://dx.doi.org/10.22038/IJBMS.2022.60306.13369 |
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author | Mehrabian, Amin Vakili-Ghartavol, Roghayyeh Mashreghi, Mohammad Shokooh Saremi, Sara Badiee, Ali Arabi, Leila Alavizadeh, Seyedeh Hoda Moosavian, Seyedeh Alia Jaafari, Mahmoud Reza |
author_facet | Mehrabian, Amin Vakili-Ghartavol, Roghayyeh Mashreghi, Mohammad Shokooh Saremi, Sara Badiee, Ali Arabi, Leila Alavizadeh, Seyedeh Hoda Moosavian, Seyedeh Alia Jaafari, Mahmoud Reza |
author_sort | Mehrabian, Amin |
collection | PubMed |
description | OBJECTIVE(S): Brain cancer treatments have mainly failed due to their inability to cross the blood-brain barrier. Several studies have confirmed the presence of glutathione (GSH) receptors on BBB’s surface, as a result, products like 2B3-101, which contain over 5% pre-inserted GSH PEGylated liposomal doxorubicin, are being tested in clinical trials. Here we conducted the PEGylated nanoliposomal doxorubicin particles that are covalently attached to the glutathione using the post-insertion technique. Compared with the pre-insertion approach, the post-insertion method is notably simpler, faster, and more cost-effective, making it ideal for large-scale pharmaceutical manufacturing. MATERIALS AND METHODS: The ligands of the DSPE PEG(2000) Maleimide-GSH were introduced in the amounts of 25, 50, 100, 200, and 400 on the available Caelyx. Following physicochemical evaluations, animal experiments such as biodistribution, fluorescence microscopy, and pharmacokinetics were done. RESULTS: In comparison with Caelyx, the 200L and 400L treatment arms were the most promising formulations. We showed that nanocarriers containing 40 times fewer GSH micelles than 2B3-101 significantly increased blood-brain barrier penetrance. Due to the expressed GSH receptors on tissues as an endogenous antioxidant, doxorubicin will likely concentrate in the liver, spleen, heart, and lung in comparison with Caelyx, according to other tissue analyses. CONCLUSION: The post-insertion technique was found a successful approach with more pharmaceutical aspects for large-scale production. Moreover, further investigations are highly recommended to determine the efficacy of 5% post-inserted GSH targeted nanoliposomes versus 2B3-101 as a similar formulation with a different preparation method. |
format | Online Article Text |
id | pubmed-9148397 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Mashhad University of Medical Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-91483972022-06-01 Preparation, characterization, and biodistribution of glutathione PEGylated nanoliposomal doxorubicin for brain drug delivery with a post-insertion approach Mehrabian, Amin Vakili-Ghartavol, Roghayyeh Mashreghi, Mohammad Shokooh Saremi, Sara Badiee, Ali Arabi, Leila Alavizadeh, Seyedeh Hoda Moosavian, Seyedeh Alia Jaafari, Mahmoud Reza Iran J Basic Med Sci Original Article OBJECTIVE(S): Brain cancer treatments have mainly failed due to their inability to cross the blood-brain barrier. Several studies have confirmed the presence of glutathione (GSH) receptors on BBB’s surface, as a result, products like 2B3-101, which contain over 5% pre-inserted GSH PEGylated liposomal doxorubicin, are being tested in clinical trials. Here we conducted the PEGylated nanoliposomal doxorubicin particles that are covalently attached to the glutathione using the post-insertion technique. Compared with the pre-insertion approach, the post-insertion method is notably simpler, faster, and more cost-effective, making it ideal for large-scale pharmaceutical manufacturing. MATERIALS AND METHODS: The ligands of the DSPE PEG(2000) Maleimide-GSH were introduced in the amounts of 25, 50, 100, 200, and 400 on the available Caelyx. Following physicochemical evaluations, animal experiments such as biodistribution, fluorescence microscopy, and pharmacokinetics were done. RESULTS: In comparison with Caelyx, the 200L and 400L treatment arms were the most promising formulations. We showed that nanocarriers containing 40 times fewer GSH micelles than 2B3-101 significantly increased blood-brain barrier penetrance. Due to the expressed GSH receptors on tissues as an endogenous antioxidant, doxorubicin will likely concentrate in the liver, spleen, heart, and lung in comparison with Caelyx, according to other tissue analyses. CONCLUSION: The post-insertion technique was found a successful approach with more pharmaceutical aspects for large-scale production. Moreover, further investigations are highly recommended to determine the efficacy of 5% post-inserted GSH targeted nanoliposomes versus 2B3-101 as a similar formulation with a different preparation method. Mashhad University of Medical Sciences 2022-03 /pmc/articles/PMC9148397/ /pubmed/35656188 http://dx.doi.org/10.22038/IJBMS.2022.60306.13369 Text en https://creativecommons.org/licenses/by/3.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/ (https://creativecommons.org/licenses/by/3.0/) ) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Mehrabian, Amin Vakili-Ghartavol, Roghayyeh Mashreghi, Mohammad Shokooh Saremi, Sara Badiee, Ali Arabi, Leila Alavizadeh, Seyedeh Hoda Moosavian, Seyedeh Alia Jaafari, Mahmoud Reza Preparation, characterization, and biodistribution of glutathione PEGylated nanoliposomal doxorubicin for brain drug delivery with a post-insertion approach |
title | Preparation, characterization, and biodistribution of glutathione PEGylated nanoliposomal doxorubicin for brain drug delivery with a post-insertion approach |
title_full | Preparation, characterization, and biodistribution of glutathione PEGylated nanoliposomal doxorubicin for brain drug delivery with a post-insertion approach |
title_fullStr | Preparation, characterization, and biodistribution of glutathione PEGylated nanoliposomal doxorubicin for brain drug delivery with a post-insertion approach |
title_full_unstemmed | Preparation, characterization, and biodistribution of glutathione PEGylated nanoliposomal doxorubicin for brain drug delivery with a post-insertion approach |
title_short | Preparation, characterization, and biodistribution of glutathione PEGylated nanoliposomal doxorubicin for brain drug delivery with a post-insertion approach |
title_sort | preparation, characterization, and biodistribution of glutathione pegylated nanoliposomal doxorubicin for brain drug delivery with a post-insertion approach |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9148397/ https://www.ncbi.nlm.nih.gov/pubmed/35656188 http://dx.doi.org/10.22038/IJBMS.2022.60306.13369 |
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