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Cited by 65Epilepsy research and treatmentNanoparticle-Based Drug DeliveryAdvanced Drug Delivery Systems

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Electroresponsive Nanoparticles Improve Antiseizure Effect of Phenytoin in Generalized Tonic-Clonic Seizures

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Wang, Yi, Ying, Xiaoying, Chen, Liying, Liu, Yao, Wang, Ying, Liang, Jiao, Xu, Cenglin, Guo, Yi, Wang, Shuang, Hu, Weiwei, Du, Yongzhong, Chen, Zhong·2016·Neurotherapeutics
DOI 10.1007/s13311-016-0431-9PMC PMC4965401
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Abstract

Previously, we developed electroresponsive hydrogel nanoparticles (ERHNPs) modified with angiopep-2 (ANG) to facilitate the delivery of the antiseizure drug phenytoin sodium (PHT). However, the electroresponsive characteristics were not verified directly in epileptic mice and the optimal preparation formula for electroresponsive ability is still unclear. Here, we further synthesized PHT-loaded ANG-ERHNPs (ANG-PHT-HNPs) and PHT-loaded nonelectroresponsive hydrogel nanoparticles (ANG-PHT-HNPs) by changing the content of sodium 4-vinylbenzene sulfonate in the preparation formulae. In vivo microdialysis analysis showed that ANG-PHT-ERHNPs not only have the characteristics of a higher distribution in the central nervous system, but also have electroresponsive ability, which resulted in a strong release of nonprotein-bound PHT during seizures. In both electrical- (maximal electrical shock) and chemical-induced (pentylenetetrazole and pilocarpine) seizure models, ANG-PHT-ERHNPs lowered the effective therapeutic doses of PHT and demonstrated the improved antiseizure effects compared with ANG-PHT-HNPs or PHT solution. These results demonstrate that ANG-ERHNPs are able to transport PHT into the brain efficiently and release them when epileptiform activity occurred, which is due to the content of sodium 4-vinylbenzene sulfonate in formula. This may change the therapeutic paradigm of existing drug treatment for epilepsy into a type of on-demand control for epilepsy in the future.

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  • Functionalization of electro-responsive nanogels with angiopep-2, a dual-targeting ligand towards LRP-1, significantly improved brain accumulation.

    “The brain accumulation of electro-responsive nanogels was significantly improved by the functionalization.”

    From The blood–brain barrier: Structure, regulation and drug delivery (2023) · cites this paper as [182]

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Metadata

Authors
Wang, Y., Ying, X., Chen, L., Liu, Y., Wang, Y., Liang, J., Xu, C., Guo, Y., Wang, S., Hu, W., Du, Y., & Chen, Z.
Affiliations
  • Zhejiang University (CN)
  • Second Affiliated Hospital of Zhejiang University (CN)
Corresponding author
Chen, Zhong
ORCID
Venue
Neurotherapeutics
Publisher
Elsevier BV
Published
2016-06
Volume
13
Issue
3
Pages
603-613
ISSN
1878-7479 (ISSN-L)
DOI
10.1007/s13311-016-0431-9
PMC
PMC4965401
OpenAlex
W2345829405
Cited by
65
References
0
Citations by year
2026: 3 · 2025: 6 · 2024: 12 · 2023: 7 · 2022: 10 · 2021: 6 · 2020: 6 · 2019: 7 · 2018: 5 · 2017: 1 · 2016: 2
FWCI
4.44
Type
journal article
Language
en
Open access
Licence
Locations
  • Neurotherapeutics (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (91332202, 81273492, 81202478, 81471316)
Topics
  • Health Sciences › Medicine › Clinical Neurology › Epilepsy research and treatment
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
Keywords
phenytoin, Angiopep-2, epilepsy, generalized tonic-clonic seizures, drug delivery, on-demand drug release, central nervous system drug distribution, pentylenetetrazole-induced seizures, pilocarpine-induced seizures, maximal electroshock seizures, antiseizure therapy
MeSH terms
Animals, Anticonvulsants, Brain, Disease Models, Animal, Epilepsy, Tonic-Clonic, Male, Phenytoin, Drug Delivery Systems, Rats, Sprague-Dawley, Hydrogel, Polyethylene Glycol Dimethacrylate, Rats, Nanoparticles

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