A tailored phytosomes based nose-to-brain drug delivery strategy: Silver bullet for Alzheimer's disease

With the aging of the population, the incidence of Alzheimer's disease (AD) has increased dramatically, causing severe medical, care, and economic burdens on society and families. The efficacy of rivastigmine hydrogen tartrate (RHT), the first-line clinical treatment, is severely limited by the...

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Main Authors: Xiao Yue, Haihua Guo, Guanlin Wang, Jieyun Li, Zizhao Zhai, Zeting Wang, Wenhao Wang, Ziyu Zhao, Xiao Xia, Chuangxin Chen, Yingtong Cui, Chuanbin Wu, Zhengwei Huang, Xuejuan Zhang
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-02-01
Series:Bioactive Materials
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Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X24004420
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author Xiao Yue
Haihua Guo
Guanlin Wang
Jieyun Li
Zizhao Zhai
Zeting Wang
Wenhao Wang
Ziyu Zhao
Xiao Xia
Chuangxin Chen
Yingtong Cui
Chuanbin Wu
Zhengwei Huang
Xuejuan Zhang
author_facet Xiao Yue
Haihua Guo
Guanlin Wang
Jieyun Li
Zizhao Zhai
Zeting Wang
Wenhao Wang
Ziyu Zhao
Xiao Xia
Chuangxin Chen
Yingtong Cui
Chuanbin Wu
Zhengwei Huang
Xuejuan Zhang
author_sort Xiao Yue
collection DOAJ
description With the aging of the population, the incidence of Alzheimer's disease (AD) has increased dramatically, causing severe medical, care, and economic burdens on society and families. The efficacy of rivastigmine hydrogen tartrate (RHT), the first-line clinical treatment, is severely limited by the complex and multiple pathogenesis of AD and low brain bioavailability caused by the blood-brain barrier (BBB). Confronting such two bottlenecks, the development of multi-target agents encapsulated BBB-bypassing drug delivery systems offer tremendous therapeutics possibilities for AD. In this study, a tailored phytosomes based nose-to-brain drug delivery system with appropriate plume was successfully designed and developed. On the one hand, Ginseng RG3-based phytosomes loaded with RHT was designed for the co-delivery of GRg3 and RHT, achieving the multi-target pharmacology for AD treatment. On the other hand, a tailored nose-to-brain drug delivery system was established for the satisfactory nose-to-brain delivery efficiency, avoiding the obstacle of BBB through bypassing it. In the pharmacodynamic study based on AD rat model, GRg3@RHT exhibited obviously synergic effect, effectively break the vicious cycle of AD progression, ultimately markedly ameliorating learning and memory ability as well as behavioral dysfunctions, and delaying the neurodegenerative process associated with AD. In addition, the strong correlation of viscosity-droplet size-plume geometry-olfactory deposition was also established, and further proved by the in vivo pharmacokinetic study, which is proposed to provide evidence to enhance nose-to-brain delivery efficiency. This study is anticipated to provide novel insights into AD treatment strategies while offering innovative ideas for drug delivery approaches targeting nervous system disorders.
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spelling doaj-art-217e6d1e96484ad4ad5ce3263cd3a8952024-12-14T06:31:39ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-02-014497115A tailored phytosomes based nose-to-brain drug delivery strategy: Silver bullet for Alzheimer's diseaseXiao Yue0Haihua Guo1Guanlin Wang2Jieyun Li3Zizhao Zhai4Zeting Wang5Wenhao Wang6Ziyu Zhao7Xiao Xia8Chuangxin Chen9Yingtong Cui10Chuanbin Wu11Zhengwei Huang12Xuejuan Zhang13State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, 510006, PR China; College of Pharmacy, Jinan University, Guangzhou, 510006, Guangdong, PR ChinaKey Lab of Yuebei Food & Medicine Resources Utilization, Medical School, Shaoguan University, Shaoguan, 512005, PR ChinaSchool of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, Guangdong, PR ChinaSchool of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, Guangdong, PR ChinaState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, 510006, PR China; College of Pharmacy, Jinan University, Guangzhou, 510006, Guangdong, PR ChinaState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, 510006, PR China; College of Pharmacy, Jinan University, Guangzhou, 510006, Guangdong, PR ChinaSchool of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, Guangdong, PR China; Corresponding author. School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, Guangdong, PR China.State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, 510006, PR China; College of Pharmacy, Jinan University, Guangzhou, 510006, Guangdong, PR ChinaState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, 510006, PR China; College of Pharmacy, Jinan University, Guangzhou, 510006, Guangdong, PR ChinaState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, 510006, PR China; College of Pharmacy, Jinan University, Guangzhou, 510006, Guangdong, PR ChinaSchool of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, Guangdong, PR ChinaState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, 510006, PR China; College of Pharmacy, Jinan University, Guangzhou, 510006, Guangdong, PR ChinaState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, 510006, PR China; College of Pharmacy, Jinan University, Guangzhou, 510006, Guangdong, PR China; Corresponding author. College of Pharmacy, Jinan University, Guangzhou, 510006, Guangdong, PR China.State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, 510006, PR China; College of Pharmacy, Jinan University, Guangzhou, 510006, Guangdong, PR China; Corresponding author. College of Pharmacy, Jinan University, Guangzhou, 510006, Guangdong, PR China.With the aging of the population, the incidence of Alzheimer's disease (AD) has increased dramatically, causing severe medical, care, and economic burdens on society and families. The efficacy of rivastigmine hydrogen tartrate (RHT), the first-line clinical treatment, is severely limited by the complex and multiple pathogenesis of AD and low brain bioavailability caused by the blood-brain barrier (BBB). Confronting such two bottlenecks, the development of multi-target agents encapsulated BBB-bypassing drug delivery systems offer tremendous therapeutics possibilities for AD. In this study, a tailored phytosomes based nose-to-brain drug delivery system with appropriate plume was successfully designed and developed. On the one hand, Ginseng RG3-based phytosomes loaded with RHT was designed for the co-delivery of GRg3 and RHT, achieving the multi-target pharmacology for AD treatment. On the other hand, a tailored nose-to-brain drug delivery system was established for the satisfactory nose-to-brain delivery efficiency, avoiding the obstacle of BBB through bypassing it. In the pharmacodynamic study based on AD rat model, GRg3@RHT exhibited obviously synergic effect, effectively break the vicious cycle of AD progression, ultimately markedly ameliorating learning and memory ability as well as behavioral dysfunctions, and delaying the neurodegenerative process associated with AD. In addition, the strong correlation of viscosity-droplet size-plume geometry-olfactory deposition was also established, and further proved by the in vivo pharmacokinetic study, which is proposed to provide evidence to enhance nose-to-brain delivery efficiency. This study is anticipated to provide novel insights into AD treatment strategies while offering innovative ideas for drug delivery approaches targeting nervous system disorders.http://www.sciencedirect.com/science/article/pii/S2452199X24004420Alzheimer's diseasePhytosomesGinseng RG3Nose-to-brain drug delivery systemMulti-target pharmacology
spellingShingle Xiao Yue
Haihua Guo
Guanlin Wang
Jieyun Li
Zizhao Zhai
Zeting Wang
Wenhao Wang
Ziyu Zhao
Xiao Xia
Chuangxin Chen
Yingtong Cui
Chuanbin Wu
Zhengwei Huang
Xuejuan Zhang
A tailored phytosomes based nose-to-brain drug delivery strategy: Silver bullet for Alzheimer's disease
Bioactive Materials
Alzheimer's disease
Phytosomes
Ginseng RG3
Nose-to-brain drug delivery system
Multi-target pharmacology
title A tailored phytosomes based nose-to-brain drug delivery strategy: Silver bullet for Alzheimer's disease
title_full A tailored phytosomes based nose-to-brain drug delivery strategy: Silver bullet for Alzheimer's disease
title_fullStr A tailored phytosomes based nose-to-brain drug delivery strategy: Silver bullet for Alzheimer's disease
title_full_unstemmed A tailored phytosomes based nose-to-brain drug delivery strategy: Silver bullet for Alzheimer's disease
title_short A tailored phytosomes based nose-to-brain drug delivery strategy: Silver bullet for Alzheimer's disease
title_sort tailored phytosomes based nose to brain drug delivery strategy silver bullet for alzheimer s disease
topic Alzheimer's disease
Phytosomes
Ginseng RG3
Nose-to-brain drug delivery system
Multi-target pharmacology
url http://www.sciencedirect.com/science/article/pii/S2452199X24004420
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