The role of size in PEGylated liposomal doxorubicin biodistribution and anti‐tumour activity

Abstract The size of nanoliposome‐encapsulated drugs significantly affects their therapeutic efficacy, biodistribution, targeting ability, and toxicity profile for the cancer treatment. In the present study, the biodistribution and anti‐tumoral activity of PEGylated liposomal Doxorubicin (PLD) formu...

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Main Authors: Saba Dadpour, Amin Mehrabian, Mahdieh Arabsalmani, Elaheh Mirhadi, Anis Askarizadeh, Mohammad Mashreghi, Mahmoud Reza Jaafari
Format: Article
Language:English
Published: Wiley 2022-09-01
Series:IET Nanobiotechnology
Subjects:
Online Access:https://doi.org/10.1049/nbt2.12094
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author Saba Dadpour
Amin Mehrabian
Mahdieh Arabsalmani
Elaheh Mirhadi
Anis Askarizadeh
Mohammad Mashreghi
Mahmoud Reza Jaafari
author_facet Saba Dadpour
Amin Mehrabian
Mahdieh Arabsalmani
Elaheh Mirhadi
Anis Askarizadeh
Mohammad Mashreghi
Mahmoud Reza Jaafari
author_sort Saba Dadpour
collection DOAJ
description Abstract The size of nanoliposome‐encapsulated drugs significantly affects their therapeutic efficacy, biodistribution, targeting ability, and toxicity profile for the cancer treatment. In the present study, the biodistribution and anti‐tumoral activity of PEGylated liposomal Doxorubicin (PLD) formulations with different sizes were investigated. First, 100, 200, and 400 nm PLDs were prepared by remote loading procedure and characterised for their size, zeta potential, encapsulation efficacy, and release properties. Then, in vitro cellular uptake and cytotoxicity were studied by flow cytometry and MTT assay, and compared with commercially available PLD Caelyx®. In vivo studies were applied on BALB/c mice bearing C26 colon carcinoma. The cytotoxicity and cellular uptake tests did not demonstrate any statistically significant differences between PLDs. The biodistribution results showed that Caelyx® and 100 nm liposomal formulations had the most doxorubicin (Dox) accumulation in the tumour tissue and, as a result, considerably suppressed tumour growth compared with 200 and 400 nm PLDs. In contrast, larger nanoparticles (200 and 400 nm formulations) had more accumulation in the liver and spleen. This study revealed that 90 nm Caelyx® biodistribution profile led to the stronger anti‐tumour activity of the drug and hence significant survival extension, and showed the importance of vesicle size in the targeting of nanoparticles to the tumour microenvironment for the treatment of cancer.
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spelling doaj-art-976762e36fb642269d4acca83f69b3d42025-02-03T06:47:36ZengWileyIET Nanobiotechnology1751-87411751-875X2022-09-01167-825927210.1049/nbt2.12094The role of size in PEGylated liposomal doxorubicin biodistribution and anti‐tumour activitySaba Dadpour0Amin Mehrabian1Mahdieh Arabsalmani2Elaheh Mirhadi3Anis Askarizadeh4Mohammad Mashreghi5Mahmoud Reza Jaafari6Nanotechnology Research Center Student Research Committee Faculty of Pharmacy Mashhad University of Medical Sciences Mashhad IranNanotechnology Research Center Pharmaceutical Technology Institute Mashhad University of Medical Sciences Mashhad IranNanotechnology Research Center Pharmaceutical Technology Institute Mashhad University of Medical Sciences Mashhad IranNanotechnology Research Center Pharmaceutical Technology Institute Mashhad University of Medical Sciences Mashhad IranNanotechnology Research Center Pharmaceutical Technology Institute Mashhad University of Medical Sciences Mashhad IranNanotechnology Research Center Pharmaceutical Technology Institute Mashhad University of Medical Sciences Mashhad IranNanotechnology Research Center Pharmaceutical Technology Institute Mashhad University of Medical Sciences Mashhad IranAbstract The size of nanoliposome‐encapsulated drugs significantly affects their therapeutic efficacy, biodistribution, targeting ability, and toxicity profile for the cancer treatment. In the present study, the biodistribution and anti‐tumoral activity of PEGylated liposomal Doxorubicin (PLD) formulations with different sizes were investigated. First, 100, 200, and 400 nm PLDs were prepared by remote loading procedure and characterised for their size, zeta potential, encapsulation efficacy, and release properties. Then, in vitro cellular uptake and cytotoxicity were studied by flow cytometry and MTT assay, and compared with commercially available PLD Caelyx®. In vivo studies were applied on BALB/c mice bearing C26 colon carcinoma. The cytotoxicity and cellular uptake tests did not demonstrate any statistically significant differences between PLDs. The biodistribution results showed that Caelyx® and 100 nm liposomal formulations had the most doxorubicin (Dox) accumulation in the tumour tissue and, as a result, considerably suppressed tumour growth compared with 200 and 400 nm PLDs. In contrast, larger nanoparticles (200 and 400 nm formulations) had more accumulation in the liver and spleen. This study revealed that 90 nm Caelyx® biodistribution profile led to the stronger anti‐tumour activity of the drug and hence significant survival extension, and showed the importance of vesicle size in the targeting of nanoparticles to the tumour microenvironment for the treatment of cancer.https://doi.org/10.1049/nbt2.12094BiodistributionCancerEPR effectNanoparticle sizePEGylated liposomal doxorubicinTherapeutic efficacy
spellingShingle Saba Dadpour
Amin Mehrabian
Mahdieh Arabsalmani
Elaheh Mirhadi
Anis Askarizadeh
Mohammad Mashreghi
Mahmoud Reza Jaafari
The role of size in PEGylated liposomal doxorubicin biodistribution and anti‐tumour activity
IET Nanobiotechnology
Biodistribution
Cancer
EPR effect
Nanoparticle size
PEGylated liposomal doxorubicin
Therapeutic efficacy
title The role of size in PEGylated liposomal doxorubicin biodistribution and anti‐tumour activity
title_full The role of size in PEGylated liposomal doxorubicin biodistribution and anti‐tumour activity
title_fullStr The role of size in PEGylated liposomal doxorubicin biodistribution and anti‐tumour activity
title_full_unstemmed The role of size in PEGylated liposomal doxorubicin biodistribution and anti‐tumour activity
title_short The role of size in PEGylated liposomal doxorubicin biodistribution and anti‐tumour activity
title_sort role of size in pegylated liposomal doxorubicin biodistribution and anti tumour activity
topic Biodistribution
Cancer
EPR effect
Nanoparticle size
PEGylated liposomal doxorubicin
Therapeutic efficacy
url https://doi.org/10.1049/nbt2.12094
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