The comparison of biodistribution of glutathione PEGylated nanoliposomal doxorubicin formulations prepared by pre‐insertion and post‐insertion methods for brain delivery in normal mice

Abstract Several obstacles limit the efficacy of brain tumour treatment, most notably the blood‐brain barrier (BBB), which prevents the brain uptake of the majority of accessible medicines due to tight junctions. The presence of glutathione (GSH) receptors on the BBB surface has been demonstrated in...

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Main Authors: Amin Mehrabian, Saba Dadpour, Mohammad Mashreghi, Javad Zarqi, Anis Askarizadeh, Ali Badiee, Leila Arabi, Seyedeh Alia Moosavian, Mahmoud Reza Jaafari
Format: Article
Language:English
Published: Wiley 2023-04-01
Series:IET Nanobiotechnology
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Online Access:https://doi.org/10.1049/nbt2.12111
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author Amin Mehrabian
Saba Dadpour
Mohammad Mashreghi
Javad Zarqi
Anis Askarizadeh
Ali Badiee
Leila Arabi
Seyedeh Alia Moosavian
Mahmoud Reza Jaafari
author_facet Amin Mehrabian
Saba Dadpour
Mohammad Mashreghi
Javad Zarqi
Anis Askarizadeh
Ali Badiee
Leila Arabi
Seyedeh Alia Moosavian
Mahmoud Reza Jaafari
author_sort Amin Mehrabian
collection DOAJ
description Abstract Several obstacles limit the efficacy of brain tumour treatment, most notably the blood‐brain barrier (BBB), which prevents the brain uptake of the majority of accessible medicines due to tight junctions. The presence of glutathione (GSH) receptors on the BBB surface has been demonstrated in numerous papers; consequently, products containing glutathione as a targeting ligand coupled with nanoliposomes are used to enhance drug delivery across the BBB. Here, the 5% pre‐inserted PEG2000‐GSH PEGylated liposomal doxorubicin was conducted according to 2B3‐101 being tested in clinical trials. In addition, PEGylated nanoliposomal doxorubicin connected to the spacer‐GSH targeting ligand (GSGGCE) and the PEG3400 was conducted using post‐insertion method. Next, in vivo biodistribution of the produced formulations was tested on healthy mice to see if GSGGCE, as the targeted ligand, could cross the BBB compared to 5% pre‐inserted PEG2000‐GSH and Caelyx®. Compared to the pre‐inserted formulation and Caelyx®, the post‐inserted formulations' concentration was lower in the heart and higher in brain tissues, resulting in boosting the brain concentration of accumulated doxorubicin with fewer possible side effects, including cardiotoxicity. In comparison to the pre‐insertion procedure, the post‐insertion method is easier, faster, and more cost‐effective. Moreover, employing PEG3400 and the post‐insertion approach in the PEG3400‐GSGGCE liposomal formulations was found to be effective in crossing the BBB.
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spelling doaj-art-daff2480ef8942baacd8e408881c310b2025-02-03T06:47:34ZengWileyIET Nanobiotechnology1751-87411751-875X2023-04-0117211212410.1049/nbt2.12111The comparison of biodistribution of glutathione PEGylated nanoliposomal doxorubicin formulations prepared by pre‐insertion and post‐insertion methods for brain delivery in normal miceAmin Mehrabian0Saba Dadpour1Mohammad Mashreghi2Javad Zarqi3Anis Askarizadeh4Ali Badiee5Leila Arabi6Seyedeh Alia Moosavian7Mahmoud Reza Jaafari8Department of Pharmaceutical Nanotechnology School of Pharmacy Mashhad University of Medical Sciences Mashhad IranDepartment of Pharmaceutical Nanotechnology School of Pharmacy Mashhad University of Medical Sciences Mashhad IranDepartment of Pharmaceutical Nanotechnology School of Pharmacy Mashhad University of Medical Sciences Mashhad IranDepartment of Pharmaceutical Nanotechnology School of Pharmacy Mashhad University of Medical Sciences Mashhad IranDepartment of Pharmaceutical Nanotechnology School of Pharmacy Mashhad University of Medical Sciences Mashhad IranDepartment of Pharmaceutical Nanotechnology School of Pharmacy Mashhad University of Medical Sciences Mashhad IranDepartment of Pharmaceutical Nanotechnology School of Pharmacy Mashhad University of Medical Sciences Mashhad IranDepartment of Pharmaceutical Nanotechnology School of Pharmacy Mashhad University of Medical Sciences Mashhad IranDepartment of Pharmaceutical Nanotechnology School of Pharmacy Mashhad University of Medical Sciences Mashhad IranAbstract Several obstacles limit the efficacy of brain tumour treatment, most notably the blood‐brain barrier (BBB), which prevents the brain uptake of the majority of accessible medicines due to tight junctions. The presence of glutathione (GSH) receptors on the BBB surface has been demonstrated in numerous papers; consequently, products containing glutathione as a targeting ligand coupled with nanoliposomes are used to enhance drug delivery across the BBB. Here, the 5% pre‐inserted PEG2000‐GSH PEGylated liposomal doxorubicin was conducted according to 2B3‐101 being tested in clinical trials. In addition, PEGylated nanoliposomal doxorubicin connected to the spacer‐GSH targeting ligand (GSGGCE) and the PEG3400 was conducted using post‐insertion method. Next, in vivo biodistribution of the produced formulations was tested on healthy mice to see if GSGGCE, as the targeted ligand, could cross the BBB compared to 5% pre‐inserted PEG2000‐GSH and Caelyx®. Compared to the pre‐inserted formulation and Caelyx®, the post‐inserted formulations' concentration was lower in the heart and higher in brain tissues, resulting in boosting the brain concentration of accumulated doxorubicin with fewer possible side effects, including cardiotoxicity. In comparison to the pre‐insertion procedure, the post‐insertion method is easier, faster, and more cost‐effective. Moreover, employing PEG3400 and the post‐insertion approach in the PEG3400‐GSGGCE liposomal formulations was found to be effective in crossing the BBB.https://doi.org/10.1049/nbt2.12111braindrug delivery systemsnanomedicinenanoparticles
spellingShingle Amin Mehrabian
Saba Dadpour
Mohammad Mashreghi
Javad Zarqi
Anis Askarizadeh
Ali Badiee
Leila Arabi
Seyedeh Alia Moosavian
Mahmoud Reza Jaafari
The comparison of biodistribution of glutathione PEGylated nanoliposomal doxorubicin formulations prepared by pre‐insertion and post‐insertion methods for brain delivery in normal mice
IET Nanobiotechnology
brain
drug delivery systems
nanomedicine
nanoparticles
title The comparison of biodistribution of glutathione PEGylated nanoliposomal doxorubicin formulations prepared by pre‐insertion and post‐insertion methods for brain delivery in normal mice
title_full The comparison of biodistribution of glutathione PEGylated nanoliposomal doxorubicin formulations prepared by pre‐insertion and post‐insertion methods for brain delivery in normal mice
title_fullStr The comparison of biodistribution of glutathione PEGylated nanoliposomal doxorubicin formulations prepared by pre‐insertion and post‐insertion methods for brain delivery in normal mice
title_full_unstemmed The comparison of biodistribution of glutathione PEGylated nanoliposomal doxorubicin formulations prepared by pre‐insertion and post‐insertion methods for brain delivery in normal mice
title_short The comparison of biodistribution of glutathione PEGylated nanoliposomal doxorubicin formulations prepared by pre‐insertion and post‐insertion methods for brain delivery in normal mice
title_sort comparison of biodistribution of glutathione pegylated nanoliposomal doxorubicin formulations prepared by pre insertion and post insertion methods for brain delivery in normal mice
topic brain
drug delivery systems
nanomedicine
nanoparticles
url https://doi.org/10.1049/nbt2.12111
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