Transferrin-Modified Osthole PEGylated Liposomes Travel the Blood-Brain Barrier and Mitigate Alzheimer’s Disease-Related Pathology in APP/PS-1 Mice
Liang Kong,1 Xue-tao Li,1 Ying-nan Ni,1 Hong-he Xiao,1 Ying-jia Yao,2 Yuan-yuan Wang,3 Rui-jun Ju,4 Hong-yan Li,1 Jing-jing Liu,1 Min Fu,1 Yu-tong Wu,1 Jing-xian Yang,1 Lan Cheng1 1School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, People’s Republic of...
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Dove Medical Press
2020
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oai:doaj.org-article:61738217a6dc4499aa0d1e60044c00012021-12-02T09:41:56ZTransferrin-Modified Osthole PEGylated Liposomes Travel the Blood-Brain Barrier and Mitigate Alzheimer’s Disease-Related Pathology in APP/PS-1 Mice1178-2013https://doaj.org/article/61738217a6dc4499aa0d1e60044c00012020-04-01T00:00:00Zhttps://www.dovepress.com/transferrin-modified-osthole-pegylated-liposomes-travel-the-blood-brai-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Liang Kong,1 Xue-tao Li,1 Ying-nan Ni,1 Hong-he Xiao,1 Ying-jia Yao,2 Yuan-yuan Wang,3 Rui-jun Ju,4 Hong-yan Li,1 Jing-jing Liu,1 Min Fu,1 Yu-tong Wu,1 Jing-xian Yang,1 Lan Cheng1 1School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, People’s Republic of China; 2College of Life and Health Sciences, Northeastern University, Shenyang 110819, People’s Republic of China; 3Department of Pharmacy, The Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning 116001, People’s Republic of China; 4Department of Pharmaceutical Engineering, Beijing Institute of Petrochemical Technology, Beijing 102617, People’s Republic of ChinaCorrespondence: Jing-xian Yang; Lan Cheng Email jingxianyang0520@163.com; sychenglan@163.comIntroduction: 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.Keywords: transferrin, osthole, liposomes, blood-brain barrier, Alzheimer’s diseaseKong LLi XNi YXiao HYao YWang YJu RLi HLiu JFu MWu YYang JCheng LDove Medical Pressarticletransferrinostholeliposomesblood-brain barrieralzheimer’s diseaseMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 2841-2858 (2020) |
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transferrin osthole liposomes blood-brain barrier alzheimer’s disease Medicine (General) R5-920 |
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transferrin osthole liposomes blood-brain barrier alzheimer’s disease Medicine (General) R5-920 Kong L Li X Ni Y Xiao H Yao Y Wang Y Ju R Li H Liu J Fu M Wu Y Yang J Cheng L Transferrin-Modified Osthole PEGylated Liposomes Travel the Blood-Brain Barrier and Mitigate Alzheimer’s Disease-Related Pathology in APP/PS-1 Mice |
| description |
Liang Kong,1 Xue-tao Li,1 Ying-nan Ni,1 Hong-he Xiao,1 Ying-jia Yao,2 Yuan-yuan Wang,3 Rui-jun Ju,4 Hong-yan Li,1 Jing-jing Liu,1 Min Fu,1 Yu-tong Wu,1 Jing-xian Yang,1 Lan Cheng1 1School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, People’s Republic of China; 2College of Life and Health Sciences, Northeastern University, Shenyang 110819, People’s Republic of China; 3Department of Pharmacy, The Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning 116001, People’s Republic of China; 4Department of Pharmaceutical Engineering, Beijing Institute of Petrochemical Technology, Beijing 102617, People’s Republic of ChinaCorrespondence: Jing-xian Yang; Lan Cheng
Email jingxianyang0520@163.com; sychenglan@163.comIntroduction: 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.Keywords: transferrin, osthole, liposomes, blood-brain barrier, Alzheimer’s disease |
| format |
article |
| author |
Kong L Li X Ni Y Xiao H Yao Y Wang Y Ju R Li H Liu J Fu M Wu Y Yang J Cheng L |
| author_facet |
Kong L Li X Ni Y Xiao H Yao Y Wang Y Ju R Li H Liu J Fu M Wu Y Yang J Cheng L |
| author_sort |
Kong L |
| title |
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_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_sort |
transferrin-modified osthole pegylated liposomes travel the blood-brain barrier and mitigate alzheimer’s disease-related pathology in app/ps-1 mice |
| publisher |
Dove Medical Press |
| publishDate |
2020 |
| url |
https://doaj.org/article/61738217a6dc4499aa0d1e60044c0001 |
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