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Transferrin-Modified Osthole PEGylated Liposomes Travel the Blood-Brain Barrier and Mitigate Alzheimer’s Disease-Related Pathology in APP/PS-1 Mice

INTRODUCTION: Osthole (Ost) is a coumarin compound that strengthens hippocampal neurons and neural stem cells against Aβ oligomer-induced neurotoxicity in mice, and is a potential drug for the treatment of Alzheimer's disease (AD). However, the effectiveness of the drug is limited by its solubi...

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Autores principales: Kong, Liang, Li, Xue-tao, Ni, Ying-nan, Xiao, Hong-he, Yao, Ying-jia, Wang, Yuan-yuan, Ju, Rui-jun, Li, Hong-yan, Liu, Jing-jing, Fu, Min, Wu, Yu-tong, Yang, Jing-xian, Cheng, Lan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186891/
https://www.ncbi.nlm.nih.gov/pubmed/32425521
http://dx.doi.org/10.2147/IJN.S239608
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author Kong, Liang
Li, Xue-tao
Ni, Ying-nan
Xiao, Hong-he
Yao, Ying-jia
Wang, Yuan-yuan
Ju, Rui-jun
Li, Hong-yan
Liu, Jing-jing
Fu, Min
Wu, Yu-tong
Yang, Jing-xian
Cheng, Lan
author_facet Kong, Liang
Li, Xue-tao
Ni, Ying-nan
Xiao, Hong-he
Yao, Ying-jia
Wang, Yuan-yuan
Ju, Rui-jun
Li, Hong-yan
Liu, Jing-jing
Fu, Min
Wu, Yu-tong
Yang, Jing-xian
Cheng, Lan
author_sort Kong, Liang
collection PubMed
description INTRODUCTION: Osthole (Ost) is a coumarin compound that strengthens hippocampal neurons and neural stem cells against Aβ oligomer-induced neurotoxicity in mice, and is a potential drug for the treatment of Alzheimer's disease (AD). However, the effectiveness of the drug is limited by its solubility and bioavailability, as well as by the low permeability of the blood-brain barrier (BBB). In this study, a kind of transferrin-modified Ost liposomes (Tf-Ost-Lip) was constructed, which could improve the bioavailability and enhance brain targeting. METHODS: Tf-Ost-Lip was prepared by thin-film hydration method. The ability of liposomal formulations to translocate across BBB was investigated using in vitro BBB model. And the protective effect of Tf-Ost-Lip was evaluated in APP-SH-SY5Y cells. In addition, we performed pharmacokinetics study and brain tissue distribution analysis of liposomal formulations in vivo. We also observed the neuroprotective effect of the varying formulations in APP/PS-1 mice. RESULTS: In vitro studies reveal that Tf-Ost-Lip could increase the intracellular uptake of hCMEC/D3 cells and APP-SH-SY5Y cells, and increase the drug concentration across the BBB. Additionally, Tf-Ost-Lip was found to exert a protective effect on APP-SH-SY5Y cells. In vivo studies of pharmacokinetics and the Ost distribution in brain tissue indicate that Tf-Ost-Lip prolonged the cycle time in mice and increased the accumulation of Ost in the brain. Furthermore, Tf-Ost-Lip was also found to enhance the effect of Ost on the alleviation of Alzheimer’s disease-related pathology. CONCLUSION: Transferrin-modified liposomes for delivery of Ost has great potential for AD treatment.
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spelling pubmed-71868912020-05-18 Transferrin-Modified Osthole PEGylated Liposomes Travel the Blood-Brain Barrier and Mitigate Alzheimer’s Disease-Related Pathology in APP/PS-1 Mice Kong, Liang Li, Xue-tao Ni, Ying-nan Xiao, Hong-he Yao, Ying-jia Wang, Yuan-yuan Ju, Rui-jun Li, Hong-yan Liu, Jing-jing Fu, Min Wu, Yu-tong Yang, Jing-xian Cheng, Lan Int J Nanomedicine Original Research INTRODUCTION: Osthole (Ost) is a coumarin compound that strengthens hippocampal neurons and neural stem cells against Aβ oligomer-induced neurotoxicity in mice, and is a potential drug for the treatment of Alzheimer's disease (AD). However, the effectiveness of the drug is limited by its solubility and bioavailability, as well as by the low permeability of the blood-brain barrier (BBB). In this study, a kind of transferrin-modified Ost liposomes (Tf-Ost-Lip) was constructed, which could improve the bioavailability and enhance brain targeting. METHODS: Tf-Ost-Lip was prepared by thin-film hydration method. The ability of liposomal formulations to translocate across BBB was investigated using in vitro BBB model. And the protective effect of Tf-Ost-Lip was evaluated in APP-SH-SY5Y cells. In addition, we performed pharmacokinetics study and brain tissue distribution analysis of liposomal formulations in vivo. We also observed the neuroprotective effect of the varying formulations in APP/PS-1 mice. RESULTS: In vitro studies reveal that Tf-Ost-Lip could increase the intracellular uptake of hCMEC/D3 cells and APP-SH-SY5Y cells, and increase the drug concentration across the BBB. Additionally, Tf-Ost-Lip was found to exert a protective effect on APP-SH-SY5Y cells. In vivo studies of pharmacokinetics and the Ost distribution in brain tissue indicate that Tf-Ost-Lip prolonged the cycle time in mice and increased the accumulation of Ost in the brain. Furthermore, Tf-Ost-Lip was also found to enhance the effect of Ost on the alleviation of Alzheimer’s disease-related pathology. CONCLUSION: Transferrin-modified liposomes for delivery of Ost has great potential for AD treatment. Dove 2020-04-23 /pmc/articles/PMC7186891/ /pubmed/32425521 http://dx.doi.org/10.2147/IJN.S239608 Text en © 2020 Kong et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Kong, Liang
Li, Xue-tao
Ni, Ying-nan
Xiao, Hong-he
Yao, Ying-jia
Wang, Yuan-yuan
Ju, Rui-jun
Li, Hong-yan
Liu, Jing-jing
Fu, Min
Wu, Yu-tong
Yang, Jing-xian
Cheng, Lan
Transferrin-Modified Osthole PEGylated Liposomes Travel the Blood-Brain Barrier and Mitigate Alzheimer’s Disease-Related Pathology in APP/PS-1 Mice
title Transferrin-Modified Osthole PEGylated Liposomes Travel the Blood-Brain Barrier and Mitigate Alzheimer’s Disease-Related Pathology in APP/PS-1 Mice
title_full Transferrin-Modified Osthole PEGylated Liposomes Travel the Blood-Brain Barrier and Mitigate Alzheimer’s Disease-Related Pathology in APP/PS-1 Mice
title_fullStr Transferrin-Modified Osthole PEGylated Liposomes Travel the Blood-Brain Barrier and Mitigate Alzheimer’s Disease-Related Pathology in APP/PS-1 Mice
title_full_unstemmed Transferrin-Modified Osthole PEGylated Liposomes Travel the Blood-Brain Barrier and Mitigate Alzheimer’s Disease-Related Pathology in APP/PS-1 Mice
title_short Transferrin-Modified Osthole PEGylated Liposomes Travel the Blood-Brain Barrier and Mitigate Alzheimer’s Disease-Related Pathology in APP/PS-1 Mice
title_sort transferrin-modified osthole pegylated liposomes travel the blood-brain barrier and mitigate alzheimer’s disease-related pathology in app/ps-1 mice
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186891/
https://www.ncbi.nlm.nih.gov/pubmed/32425521
http://dx.doi.org/10.2147/IJN.S239608
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