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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BMC
2024-04-01
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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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id | doaj.art-427bdbdd70e247fe9845372085b90a53 |
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issn | 1477-3155 |
language | English |
last_indexed | 2024-04-24T12:35:59Z |
publishDate | 2024-04-01 |
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series | Journal of Nanobiotechnology |
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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