• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

靶向脂质体共递送多巴胺与3-正丁基苯酞对小鼠帕金森病模型的有效治疗作用

Targeted Liposomal Co-Delivery Dopamine with 3-n-Butylphthalide for Effective Against Parkinson's Disease in Mice Model.

作者信息

Liang Yi, Feng Liping, Zheng Yue, Gao Yunzhen, Shi Rongying, Zhang Zhirong, Ying Xue, Zeng Yingchun

机构信息

School of Pharmacy, Chengdu Medical College, Chengdu, 610500, People's Republic of China.

Key Laboratory of Drug-Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, 610041, People's Republic of China.

出版信息

Int J Nanomedicine. 2024 Nov 30;19:12851-12870. doi: 10.2147/IJN.S483595. eCollection 2024.

DOI:10.2147/IJN.S483595
PMID:39640048
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11618862/
Abstract

INTRODUCTION

Parkinson's disease (PD) is a multifactor-induced neurodegenerative disease with high incidence in the elderly population. We found for the first time that the combination of dopamine (DA) and 3-n-butylphthalide (NBP) has great potential for the synergistic treatment of PD. To further improve the therapeutic performance of the drugs, a brain-targeting liposomal co-delivery system encapsulating NBP and DA ((NBP+DA)-Lips-RVG29) was designed using a rabies virus polypeptide with 29 amino acids (RVG29) as the targeting ligand.

METHODS

The synergistic neuroprotective effects of NBP and DA were assessed in 6-OHDA-induced PC12 cells. Then, (NBP+DA)-Lips-RVG29 loading with NBP and DA at an optimal ratio was prepared using the thin-film hydration and sonication method. The physicochemical and biological characterization of (NBP+DA)-Lips-RVG29 were systemically investigated, and the therapeutic efficiency and underlying mechanisms of (NBP+DA)-Lips-RVG29 were also explored in vitro and in vivo. Finally, the safety of (NBP+DA)-Lips-RVG29 was evaluated.

RESULTS

The synergistic effects of NBP and DA peaked at 1:1 (NBP/DA, mol/mol). The functionalized liposomes showed significantly higher uptake efficiency and blood-brain barrier (BBB) penetration efficiency in vitro. After systemic administration, (NBP+DA)-Lips-RVG29 prolonged the blood circulation of drugs, enhanced BBB penetration and increased drug accumulation in the striatum, substantia nigra and hippocampus. Moreover, (NBP+DA)-Lips-RVG29 showed excellent neuroprotective effects in a cellular PD model of PC12 cells and improved therapeutic efficacy in a PD mouse model. Furthermore, the safety evaluation of (NBP+DA)-Lips-RVG29 revealed no systemic toxicity.

CONCLUSION

NBP and DA exhibited the synergistic anti-PD effects. The RVG29-modified liposomes encapsulating NBP and DA contributed to the accumulation of drugs in the brain lesions area of PD and further improved treatment efficacy. Therefore, (NBP+DA)-Lips-RVG29 represents a promising strategy for the treatment of PD and other neurodegenerative diseases.

摘要

引言

帕金森病（PD）是一种多因素诱发的神经退行性疾病，在老年人群中发病率较高。我们首次发现多巴胺（DA）与3-正丁基苯酞（NBP）联合使用在协同治疗PD方面具有巨大潜力。为进一步提高药物的治疗效果，以29个氨基酸的狂犬病毒多肽（RVG29）为靶向配体，设计了一种包封NBP和DA的脑靶向脂质体共递送系统（(NBP+DA)-Lips-RVG29）。

方法

在6-羟基多巴胺（6-OHDA）诱导的PC12细胞中评估NBP和DA的协同神经保护作用。然后，采用薄膜水化和超声法制备以最佳比例负载NBP和DA的(NBP+DA)-Lips-RVG29。系统研究了(NBP+DA)-Lips-RVG29的理化性质和生物学特性，并在体外和体内探索了(NBP+DA)-Lips-RVG29的治疗效果及潜在机制。最后，评估了(NBP+DA)-Lips-RVG29的安全性。

结果

NBP和DA的协同作用在1:1（NBP/DA，摩尔/摩尔）时达到峰值。功能化脂质体在体外显示出显著更高的摄取效率和血脑屏障（BBB）穿透效率。全身给药后，(NBP+DA)-Lips-RVG29延长了药物的血液循环时间，增强了BBB穿透能力，并增加了药物在纹状体、黑质和海马体中的蓄积。此外，(NBP+DA)-Lips-RVG29在PC12细胞的细胞性PD模型中显示出优异的神经保护作用，并在PD小鼠模型中提高了治疗效果。此外，(NBP+DA)-Lips-RVG29的安全性评估显示无全身毒性。

结论

NBP和DA表现出协同抗PD作用。包封NBP和DA的RVG29修饰脂质体有助于药物在PD脑损伤区域的蓄积，并进一步提高治疗效果。因此，(NBP+DA)-Lips-RVG29是治疗PD和其他神经退行性疾病的一种有前景的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/581b/11618862/e5823ed40afc/IJN-19-12851-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/581b/11618862/83b8be1a0d68/IJN-19-12851-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/581b/11618862/66dac3b5a998/IJN-19-12851-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/581b/11618862/d1259c406d9f/IJN-19-12851-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/581b/11618862/d45cbfb685ab/IJN-19-12851-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/581b/11618862/b1023d497be7/IJN-19-12851-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/581b/11618862/3ad874d68740/IJN-19-12851-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/581b/11618862/c5b6936444ff/IJN-19-12851-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/581b/11618862/e21eb104e409/IJN-19-12851-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/581b/11618862/e5823ed40afc/IJN-19-12851-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/581b/11618862/83b8be1a0d68/IJN-19-12851-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/581b/11618862/66dac3b5a998/IJN-19-12851-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/581b/11618862/d1259c406d9f/IJN-19-12851-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/581b/11618862/d45cbfb685ab/IJN-19-12851-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/581b/11618862/b1023d497be7/IJN-19-12851-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/581b/11618862/3ad874d68740/IJN-19-12851-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/581b/11618862/c5b6936444ff/IJN-19-12851-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/581b/11618862/e21eb104e409/IJN-19-12851-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/581b/11618862/e5823ed40afc/IJN-19-12851-g0009.jpg

相似文献

1
Targeted Liposomal Co-Delivery Dopamine with 3-n-Butylphthalide for Effective Against Parkinson's Disease in Mice Model.靶向脂质体共递送多巴胺与3-正丁基苯酞对小鼠帕金森病模型的有效治疗作用
Int J Nanomedicine. 2024 Nov 30;19:12851-12870. doi: 10.2147/IJN.S483595. eCollection 2024.
2
A brain targeting functionalized liposomes of the dopamine derivative N-3,4-bis(pivaloyloxy)-dopamine for treatment of Parkinson's disease.用于治疗帕金森病的多巴胺衍生物 N-3,4-双（特戊酰氧基）-多巴胺脑靶向功能化脂质体。
J Control Release. 2018 May 10;277:173-182. doi: 10.1016/j.jconrel.2018.03.019. Epub 2018 Mar 26.
3
Use of PEGylated Immunoliposomes to Deliver Dopamine Across the Blood-Brain Barrier in a Rat Model of Parkinson's Disease.聚乙二醇化免疫脂质体在帕金森病大鼠模型中用于跨越血脑屏障递送多巴胺的研究。
CNS Neurosci Ther. 2016 Oct;22(10):817-23. doi: 10.1111/cns.12580. Epub 2016 Jun 27.
4
Rapid and improved oral absorption of N-butylphthalide by sodium cholate-appended liposomes for efficient ischemic stroke therapy.胆酸钠修饰的脂质体提高丁苯酞的口服吸收用于有效治疗缺血性脑卒中。
Drug Deliv. 2021 Dec;28(1):2469-2479. doi: 10.1080/10717544.2021.2000678.
5
Key Lipoprotein Receptor Targeted Echinacoside-Liposomes Effective Against Parkinson's Disease in Mice Model.靶向关键脂蛋白受体的毛菊苣苷脂质体对小鼠帕金森病模型有效。
Int J Nanomedicine. 2024 Aug 19;19:8463-8483. doi: 10.2147/IJN.S468942. eCollection 2024.
6
Trojan Horse Delivery of 4,4'-Dimethoxychalcone for Parkinsonian Neuroprotection.4,4'-二甲氧基查耳酮经木马载体传递用于帕金森病神经保护。
Adv Sci (Weinh). 2021 Mar 3;8(9):2004555. doi: 10.1002/advs.202004555. eCollection 2021 May.
7
Combining nanoscale magnetic nimodipine liposomes with magnetic resonance image for Parkinson's disease targeting therapy.将纳米级磁性尼莫地平脂质体与磁共振成像相结合，用于帕金森病的靶向治疗。
Nanomedicine (Lond). 2017 Feb;12(3):237-253. doi: 10.2217/nnm-2016-0267. Epub 2017 Jan 17.
8
Dl-3-n-Butylphthalide Rescues Dopaminergic Neurons in Parkinson's Disease Models by Inhibiting the NLRP3 Inflammasome and Ameliorating Mitochondrial Impairment.DL-3-正丁基苯酞通过抑制 NLRP3 炎性小体和改善线粒体损伤来拯救帕金森病模型中的多巴胺能神经元。
Front Immunol. 2021 Dec 1;12:794770. doi: 10.3389/fimmu.2021.794770. eCollection 2021.
9
Parkinson Disease -Targeted Nanocapsules for Synergistic Treatment: Combining Dopamine Replacement and Neuroinflammation Mitigation.帕金森病——用于协同治疗的靶向纳米胶囊：结合多巴胺替代与神经炎症缓解
Adv Sci (Weinh). 2024 Dec;11(46):e2404717. doi: 10.1002/advs.202404717. Epub 2024 Oct 21.
10
Dl-3-n-butylphthalide, a natural antioxidant, protects dopamine neurons in rotenone models for Parkinson's disease.二丁基苯酞，一种天然抗氧化剂，可保护鱼藤酮诱导的帕金森病模型中的多巴胺神经元。
Neurobiol Aging. 2012 Aug;33(8):1777-91. doi: 10.1016/j.neurobiolaging.2011.03.007. Epub 2011 Apr 23.

本文引用的文献

1
Interaction of RAGE with α-synuclein fibrils mediates inflammatory response of microglia.RAGE 与α-突触核蛋白纤维相互作用介导小胶质细胞的炎症反应。
Cell Rep. 2022 Sep 20;40(12):111401. doi: 10.1016/j.celrep.2022.111401.
2
Brain Co-Delivery of Temozolomide and Cisplatin for Combinatorial Glioblastoma Chemotherapy.脑内共递送替莫唑胺和顺铂用于胶质母细胞瘤联合化疗。
Adv Mater. 2022 Aug;34(33):e2203958. doi: 10.1002/adma.202203958. Epub 2022 Jul 17.
3
Initiation and progression of α-synuclein pathology in Parkinson's disease.帕金森病中α-突触核蛋白病的起始和进展。
Cell Mol Life Sci. 2022 Mar 26;79(4):210. doi: 10.1007/s00018-022-04240-2.
4
Nanoreactor for cascade reaction between SOD and CAT and its tissue regeneration effect.用于超氧化物歧化酶（SOD）与过氧化氢酶（CAT）之间级联反应的纳米反应器及其组织再生效果。
J Control Release. 2022 Apr;344:160-172. doi: 10.1016/j.jconrel.2022.02.033. Epub 2022 Mar 3.
5
Inflammation and immune dysfunction in Parkinson disease.帕金森病中的炎症和免疫功能障碍。
Nat Rev Immunol. 2022 Nov;22(11):657-673. doi: 10.1038/s41577-022-00684-6. Epub 2022 Mar 4.
6
Dl-3-n-Butylphthalide Rescues Dopaminergic Neurons in Parkinson's Disease Models by Inhibiting the NLRP3 Inflammasome and Ameliorating Mitochondrial Impairment.DL-3-正丁基苯酞通过抑制 NLRP3 炎性小体和改善线粒体损伤来拯救帕金森病模型中的多巴胺能神经元。
Front Immunol. 2021 Dec 1;12:794770. doi: 10.3389/fimmu.2021.794770. eCollection 2021.
7
Parkinson's Disease Dementia: Synergistic Effects of Alpha-Synuclein, Tau, Beta-Amyloid, and Iron.帕金森病痴呆：α-突触核蛋白、tau蛋白、β-淀粉样蛋白和铁的协同作用
Front Aging Neurosci. 2021 Oct 11;13:743754. doi: 10.3389/fnagi.2021.743754. eCollection 2021.
8
Current Therapies in Clinical Trials of Parkinson's Disease: A 2021 Update.帕金森病临床试验的当前疗法：2021年更新
Pharmaceuticals (Basel). 2021 Jul 25;14(8):717. doi: 10.3390/ph14080717.
9
Novel brain-targeting 3-n-butylphthalide prodrugs for ischemic stroke treatment.新型脑靶向 3-正丁基苯酞前药治疗缺血性脑卒中。
J Control Release. 2021 Jul 10;335:498-514. doi: 10.1016/j.jconrel.2021.05.045. Epub 2021 Jun 1.
10
Trojan Horse Delivery of 4,4'-Dimethoxychalcone for Parkinsonian Neuroprotection.4,4'-二甲氧基查耳酮经木马载体传递用于帕金森病神经保护。
Adv Sci (Weinh). 2021 Mar 3;8(9):2004555. doi: 10.1002/advs.202004555. eCollection 2021 May.