Multifunctional icariin and tanshinone IIA co-delivery liposomes with potential application for Alzheimer’s disease
The blood–brain barrier (BBB) is a protective barrier for brain safety, but it is also a major obstacle to the delivery of drugs to the cerebral parenchyma such as the hippocampus, hindering the treatment of central nervous system diseases such as Alzheimer’s disease (AD). In this work, an anti-AD b...
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Taylor & Francis Group
2022-12-01
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Series: | Drug Delivery |
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Online Access: | https://www.tandfonline.com/doi/10.1080/10717544.2022.2072543 |
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author | Jiao Wang Liang Kong Rui-Bo Guo Si-Yu He Xin-Ze Liu Lu Zhang Yang Liu Yang Yu Xue-Tao Li Lan Cheng |
author_facet | Jiao Wang Liang Kong Rui-Bo Guo Si-Yu He Xin-Ze Liu Lu Zhang Yang Liu Yang Yu Xue-Tao Li Lan Cheng |
author_sort | Jiao Wang |
collection | DOAJ |
description | The blood–brain barrier (BBB) is a protective barrier for brain safety, but it is also a major obstacle to the delivery of drugs to the cerebral parenchyma such as the hippocampus, hindering the treatment of central nervous system diseases such as Alzheimer’s disease (AD). In this work, an anti-AD brain-targeted nanodrug delivery system by co-loading icariin (ICA) and tanshinone IIA (TSIIA) into Aniopep-2-modified long-circulating (Ang2-ICA/TSIIA) liposomes was developed. Low-density lipoprotein receptor-related protein-1 (LRP1) was a receptor overexpressed on the BBB. Angiopep-2, a specific ligand of LRP1, exhibited a high binding efficiency with LRP1. Additionally, ICA and TSIIA, drugs with neuroprotective effects are loaded into the liposomes, so that the liposomes not only have an effective BBB penetration effect, but also have a potential anti-AD effect. The prepared Ang2-ICA/TSIIA liposomes appeared narrow dispersity and good stability with a diameter of 110 nm, and a round morphology. Cell uptake observations, BBB models in vitro, and imaging analysis in vivo showed that Ang2-ICA/TSIIA liposomes not only penetrate the BBB through endocytosis, but also accumulate in N2a cells or brain tissue. The pharmacodynamic analysis in vivo demonstrated that Ang2-ICA/TSIIA liposomes could improve AD-like pathological features in APP/PS1 mice, including inhibiting neuroinflammation and oxidative stress, reducing apoptosis, protecting neurons, and improving cognitive function. Therefore, Ang2-ICA/TSIIA liposomes are considered a potentially effective therapeutic strategy for AD. |
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language | English |
last_indexed | 2024-12-12T09:02:43Z |
publishDate | 2022-12-01 |
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series | Drug Delivery |
spelling | doaj.art-6d9a6f9b1105415ab5242db5c0e05d4e2022-12-22T00:29:46ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642022-12-012911648166210.1080/10717544.2022.2072543Multifunctional icariin and tanshinone IIA co-delivery liposomes with potential application for Alzheimer’s diseaseJiao Wang0Liang Kong1Rui-Bo Guo2Si-Yu He3Xin-Ze Liu4Lu Zhang5Yang Liu6Yang Yu7Xue-Tao Li8Lan Cheng9School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, ChinaSchool of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, ChinaSchool of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, ChinaSchool of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, ChinaSchool of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, ChinaSchool of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, ChinaSchool of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, ChinaSchool of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, ChinaSchool of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, ChinaSchool of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, ChinaThe blood–brain barrier (BBB) is a protective barrier for brain safety, but it is also a major obstacle to the delivery of drugs to the cerebral parenchyma such as the hippocampus, hindering the treatment of central nervous system diseases such as Alzheimer’s disease (AD). In this work, an anti-AD brain-targeted nanodrug delivery system by co-loading icariin (ICA) and tanshinone IIA (TSIIA) into Aniopep-2-modified long-circulating (Ang2-ICA/TSIIA) liposomes was developed. Low-density lipoprotein receptor-related protein-1 (LRP1) was a receptor overexpressed on the BBB. Angiopep-2, a specific ligand of LRP1, exhibited a high binding efficiency with LRP1. Additionally, ICA and TSIIA, drugs with neuroprotective effects are loaded into the liposomes, so that the liposomes not only have an effective BBB penetration effect, but also have a potential anti-AD effect. The prepared Ang2-ICA/TSIIA liposomes appeared narrow dispersity and good stability with a diameter of 110 nm, and a round morphology. Cell uptake observations, BBB models in vitro, and imaging analysis in vivo showed that Ang2-ICA/TSIIA liposomes not only penetrate the BBB through endocytosis, but also accumulate in N2a cells or brain tissue. The pharmacodynamic analysis in vivo demonstrated that Ang2-ICA/TSIIA liposomes could improve AD-like pathological features in APP/PS1 mice, including inhibiting neuroinflammation and oxidative stress, reducing apoptosis, protecting neurons, and improving cognitive function. Therefore, Ang2-ICA/TSIIA liposomes are considered a potentially effective therapeutic strategy for AD.https://www.tandfonline.com/doi/10.1080/10717544.2022.2072543Angiopep-2icariintanshinone IIAliposomesAlzheimer’s disease |
spellingShingle | Jiao Wang Liang Kong Rui-Bo Guo Si-Yu He Xin-Ze Liu Lu Zhang Yang Liu Yang Yu Xue-Tao Li Lan Cheng Multifunctional icariin and tanshinone IIA co-delivery liposomes with potential application for Alzheimer’s disease Drug Delivery Angiopep-2 icariin tanshinone IIA liposomes Alzheimer’s disease |
title | Multifunctional icariin and tanshinone IIA co-delivery liposomes with potential application for Alzheimer’s disease |
title_full | Multifunctional icariin and tanshinone IIA co-delivery liposomes with potential application for Alzheimer’s disease |
title_fullStr | Multifunctional icariin and tanshinone IIA co-delivery liposomes with potential application for Alzheimer’s disease |
title_full_unstemmed | Multifunctional icariin and tanshinone IIA co-delivery liposomes with potential application for Alzheimer’s disease |
title_short | Multifunctional icariin and tanshinone IIA co-delivery liposomes with potential application for Alzheimer’s disease |
title_sort | multifunctional icariin and tanshinone iia co delivery liposomes with potential application for alzheimer s disease |
topic | Angiopep-2 icariin tanshinone IIA liposomes Alzheimer’s disease |
url | https://www.tandfonline.com/doi/10.1080/10717544.2022.2072543 |
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