Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery : LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects
INTRODUCTION: Efficient delivery of rotigotine into the brain is crucial for obtaining maximum therapeutic efficacy for Parkinson's disease (PD). Therefore, in the present study, we prepared lactoferrin-modified rotigotine nanoparticles (Lf-R-NPs) and studied their biodistribution, pharmacodynamics, and neuroprotective effects following nose-to-brain delivery in the rat 6-hydroxydopamine model of PD.
MATERIALS AND METHODS: The biodistribution of rotigotine nanoparticles (R-NPs) and Lf-R-NPs after intranasal administration was assessed by liquid extraction surface analysis coupled with tandem mass spectrometry. Contralateral rotations were quantified to evaluate pharmacodynamics. Tyrosine hydroxylase and dopamine transporter immunohistochemistry were performed to compare the neuroprotective effects of levodopa, R-NPs, and Lf-R-NPs.
RESULTS: Liquid extraction surface analysis coupled with tandem mass spectrometry analysis, used to examine rotigotine biodistribution, showed that Lf-R-NPs more efficiently supplied rotigotine to the brain (with a greater sustained amount of the drug delivered to this organ, and with more effective targeting to the striatum) than R-NPs. The pharmacodynamic study revealed a significant difference (P<0.05) in contralateral rotations between rats treated with Lf-R-NPs and those treated with R-NPs. Furthermore, Lf-R-NPs significantly alleviated nigrostriatal dopaminergic neurodegeneration in the rat model of 6-hydroxydopamine-induced PD.
CONCLUSION: Our findings show that Lf-R-NPs deliver rotigotine more efficiently to the brain, thereby enhancing efficacy. Therefore, Lf-R-NPs might have therapeutic potential for the treatment of PD.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
International journal of nanomedicine - 13(2018) vom: 21., Seite 273-281 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yan, Xiuju [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 29.05.2018 Date Revised 11.03.2022 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.2147/IJN.S151475 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM280517394 |
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| 100 | 1 | |a Yan, Xiuju |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery |b LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects |
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| 500 | |a Date Revised 11.03.2022 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a INTRODUCTION: Efficient delivery of rotigotine into the brain is crucial for obtaining maximum therapeutic efficacy for Parkinson's disease (PD). Therefore, in the present study, we prepared lactoferrin-modified rotigotine nanoparticles (Lf-R-NPs) and studied their biodistribution, pharmacodynamics, and neuroprotective effects following nose-to-brain delivery in the rat 6-hydroxydopamine model of PD | ||
| 520 | |a MATERIALS AND METHODS: The biodistribution of rotigotine nanoparticles (R-NPs) and Lf-R-NPs after intranasal administration was assessed by liquid extraction surface analysis coupled with tandem mass spectrometry. Contralateral rotations were quantified to evaluate pharmacodynamics. Tyrosine hydroxylase and dopamine transporter immunohistochemistry were performed to compare the neuroprotective effects of levodopa, R-NPs, and Lf-R-NPs | ||
| 520 | |a RESULTS: Liquid extraction surface analysis coupled with tandem mass spectrometry analysis, used to examine rotigotine biodistribution, showed that Lf-R-NPs more efficiently supplied rotigotine to the brain (with a greater sustained amount of the drug delivered to this organ, and with more effective targeting to the striatum) than R-NPs. The pharmacodynamic study revealed a significant difference (P<0.05) in contralateral rotations between rats treated with Lf-R-NPs and those treated with R-NPs. Furthermore, Lf-R-NPs significantly alleviated nigrostriatal dopaminergic neurodegeneration in the rat model of 6-hydroxydopamine-induced PD | ||
| 520 | |a CONCLUSION: Our findings show that Lf-R-NPs deliver rotigotine more efficiently to the brain, thereby enhancing efficacy. Therefore, Lf-R-NPs might have therapeutic potential for the treatment of PD | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Parkinson’s disease | |
| 650 | 4 | |a drug biodistribution | |
| 650 | 4 | |a lactoferrin-modified rotigotine nanoparticles | |
| 650 | 4 | |a neuroprotective effects | |
| 650 | 4 | |a nose to brain | |
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| 700 | 1 | |a Xu, Lixiao |e verfasserin |4 aut | |
| 700 | 1 | |a Bi, Chenchen |e verfasserin |4 aut | |
| 700 | 1 | |a Duan, Dongyu |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, Liuxiang |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Zimei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Aiping |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Kaoxiang |e verfasserin |4 aut | |
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