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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Main Authors: Jiao Wang, Liang Kong, Rui-Bo Guo, Si-Yu He, Xin-Ze Liu, Lu Zhang, Yang Liu, Yang Yu, Xue-Tao Li, Lan Cheng
Format: Article
Language:English
Published: Taylor & Francis Group 2022-12-01
Series:Drug Delivery
Subjects:
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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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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