Intranasal delivery of phenytoin loaded layered double hydroxide nanoparticles improves therapeutic effect on epileptic seizures

Abstract Improving the efficiency of antiseizure medication entering the brain is the key to reducing its peripheral toxicity. A combination of intranasal administration and nanomedicine presents a practical approach for treating epileptic seizures via bypassing the blood-brain barrier. In this stud...

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Main Authors: Jingxin Zhang, Huali Zuo, Yanlu Fu, Yina Cao, Qiwei Li, Qi Zhang, Yuyi Zheng, Yi Wang, Di Wu, Weiyu Chen, Jiajia Fang
Format: Article
Language:English
Published: BMC 2024-04-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:https://doi.org/10.1186/s12951-024-02405-8
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author Jingxin Zhang
Huali Zuo
Yanlu Fu
Yina Cao
Qiwei Li
Qi Zhang
Yuyi Zheng
Yi Wang
Di Wu
Weiyu Chen
Jiajia Fang
author_facet Jingxin Zhang
Huali Zuo
Yanlu Fu
Yina Cao
Qiwei Li
Qi Zhang
Yuyi Zheng
Yi Wang
Di Wu
Weiyu Chen
Jiajia Fang
author_sort Jingxin Zhang
collection DOAJ
description Abstract Improving the efficiency of antiseizure medication entering the brain is the key to reducing its peripheral toxicity. A combination of intranasal administration and nanomedicine presents a practical approach for treating epileptic seizures via bypassing the blood-brain barrier. In this study, phenytoin (PHT) loaded layered double hydroxide nanoparticles (BSA-LDHs-PHT) were fabricated via a coprecipitation − hydrothermal method for epileptic seizure control. In this study, we expound on the preparation method and characterization of BSA-LDHs-PHT. In-vitro drug release experiment shows both rapid and continuous drug release from BSA-LDHs-PHT, which is crucial for acute seizure control and chronic epilepsy therapy. In-vivo biodistribution assays after intranasal administration indicate excellent brain targeting ability of BSA-LDHs. Compared to BSA-Cyanine5.5, BSA-LDHs-Cyanine5.5 were associated with a higher brain/peripheral ratio across all tested time points. Following intranasal delivery with small doses of BSA-LDHs-PHT, the latency of seizures in the pentylenetetrazole-induced mouse models was effectively improved. Collectively, the present study successfully designed and applied BSA-LDHs-PHT as a promising strategy for treating epileptic seizures with an enhanced therapeutic effect.
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spelling doaj.art-427bdbdd70e247fe9845372085b90a532024-04-07T11:29:19ZengBMCJournal of Nanobiotechnology1477-31552024-04-0122111410.1186/s12951-024-02405-8Intranasal delivery of phenytoin loaded layered double hydroxide nanoparticles improves therapeutic effect on epileptic seizuresJingxin Zhang0Huali Zuo1Yanlu Fu2Yina Cao3Qiwei Li4Qi Zhang5Yuyi Zheng6Yi Wang7Di Wu8Weiyu Chen9Jiajia Fang10Department of Neurology, The Fourth Affiliated Hospital, Zhejiang University School of MedicineThe Fourth Affiliated Hospital, Zhejiang University School of MedicineDepartment of Neurology, The Fourth Affiliated Hospital, Zhejiang University School of MedicineDepartment of Neurology, The Fourth Affiliated Hospital, Zhejiang University School of MedicineDepartment of Neurology, The Fourth Affiliated Hospital, Zhejiang University School of MedicineKey Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, School of Pharmaceutical Sciences, Zhejiang Chinese Medical UniversityKey Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, School of Pharmaceutical Sciences, Zhejiang Chinese Medical UniversityKey Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, School of Pharmaceutical Sciences, Zhejiang Chinese Medical UniversityKey Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, School of Pharmaceutical Sciences, Zhejiang Chinese Medical UniversityDepartment of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital, Zhejiang University School of MedicineDepartment of Neurology, The Fourth Affiliated Hospital, Zhejiang University School of MedicineAbstract Improving the efficiency of antiseizure medication entering the brain is the key to reducing its peripheral toxicity. A combination of intranasal administration and nanomedicine presents a practical approach for treating epileptic seizures via bypassing the blood-brain barrier. In this study, phenytoin (PHT) loaded layered double hydroxide nanoparticles (BSA-LDHs-PHT) were fabricated via a coprecipitation − hydrothermal method for epileptic seizure control. In this study, we expound on the preparation method and characterization of BSA-LDHs-PHT. In-vitro drug release experiment shows both rapid and continuous drug release from BSA-LDHs-PHT, which is crucial for acute seizure control and chronic epilepsy therapy. In-vivo biodistribution assays after intranasal administration indicate excellent brain targeting ability of BSA-LDHs. Compared to BSA-Cyanine5.5, BSA-LDHs-Cyanine5.5 were associated with a higher brain/peripheral ratio across all tested time points. Following intranasal delivery with small doses of BSA-LDHs-PHT, the latency of seizures in the pentylenetetrazole-induced mouse models was effectively improved. Collectively, the present study successfully designed and applied BSA-LDHs-PHT as a promising strategy for treating epileptic seizures with an enhanced therapeutic effect.https://doi.org/10.1186/s12951-024-02405-8EpilepsyPhenytoinIntranasal deliveryLayered double hydroxide nanoparticles
spellingShingle Jingxin Zhang
Huali Zuo
Yanlu Fu
Yina Cao
Qiwei Li
Qi Zhang
Yuyi Zheng
Yi Wang
Di Wu
Weiyu Chen
Jiajia Fang
Intranasal delivery of phenytoin loaded layered double hydroxide nanoparticles improves therapeutic effect on epileptic seizures
Journal of Nanobiotechnology
Epilepsy
Phenytoin
Intranasal delivery
Layered double hydroxide nanoparticles
title Intranasal delivery of phenytoin loaded layered double hydroxide nanoparticles improves therapeutic effect on epileptic seizures
title_full Intranasal delivery of phenytoin loaded layered double hydroxide nanoparticles improves therapeutic effect on epileptic seizures
title_fullStr Intranasal delivery of phenytoin loaded layered double hydroxide nanoparticles improves therapeutic effect on epileptic seizures
title_full_unstemmed Intranasal delivery of phenytoin loaded layered double hydroxide nanoparticles improves therapeutic effect on epileptic seizures
title_short Intranasal delivery of phenytoin loaded layered double hydroxide nanoparticles improves therapeutic effect on epileptic seizures
title_sort intranasal delivery of phenytoin loaded layered double hydroxide nanoparticles improves therapeutic effect on epileptic seizures
topic Epilepsy
Phenytoin
Intranasal delivery
Layered double hydroxide nanoparticles
url https://doi.org/10.1186/s12951-024-02405-8
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