Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects

Xiuju Yan,1,* Lixiao Xu,1,* Chenchen Bi,1 Dongyu Duan,1 Liuxiang Chu,1 Xin Yu,1 Zimei Wu,1 Aiping Wang,1,2 Kaoxiang Sun1,2 1School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology an...

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Autores principales:	Yan X, Xu L, Bi C, Duan D, Chu L, Yu X, Wu Z, Wang A, Sun K
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	lactoferrin-modified rotigotine nanoparticles nose to brain drug biodistribution pharmacodynamics neuroprotective effects Parkinson’s disease Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/0632cb91d97a4d2cbb5c29aab52f0d36
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spelling	oai:doaj.org-article:0632cb91d97a4d2cbb5c29aab52f0d362021-12-02T02:10:28ZLactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects1178-2013https://doaj.org/article/0632cb91d97a4d2cbb5c29aab52f0d362018-01-01T00:00:00Zhttps://www.dovepress.com/lactoferrin-modified-rotigotine-nanoparticles-for-enhanced-nose-to-bra-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xiuju Yan,1,* Lixiao Xu,1,* Chenchen Bi,1 Dongyu Duan,1 Liuxiang Chu,1 Xin Yu,1 Zimei Wu,1 Aiping Wang,1,2 Kaoxiang Sun1,2 1School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, Shandong Province, 2State Key Laboratory of Long-Acting and Targeting Drug Delivery System, Shandong Luye Pharmaceutical Co., Ltd, Yantai, Shandong Province, People’s Republic of China *These authors contributed equally to this work 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. Keywords: lactoferrin-modified rotigotine nanoparticles, nose to brain, drug biodistribution, pharmacodynamics, neuroprotective effects, Parkinson’s diseaseYan XXu LBi CDuan DChu LYu XWu ZWang ASun KDove Medical Pressarticlelactoferrin-modified rotigotine nanoparticlesnose to braindrug biodistributionpharmacodynamicsneuroprotective effectsParkinson’s diseaseMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 273-281 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	lactoferrin-modified rotigotine nanoparticles nose to brain drug biodistribution pharmacodynamics neuroprotective effects Parkinson’s disease Medicine (General) R5-920
spellingShingle	lactoferrin-modified rotigotine nanoparticles nose to brain drug biodistribution pharmacodynamics neuroprotective effects Parkinson’s disease Medicine (General) R5-920 Yan X Xu L Bi C Duan D Chu L Yu X Wu Z Wang A Sun K Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects
description	Xiuju Yan,1,* Lixiao Xu,1,* Chenchen Bi,1 Dongyu Duan,1 Liuxiang Chu,1 Xin Yu,1 Zimei Wu,1 Aiping Wang,1,2 Kaoxiang Sun1,2 1School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, Shandong Province, 2State Key Laboratory of Long-Acting and Targeting Drug Delivery System, Shandong Luye Pharmaceutical Co., Ltd, Yantai, Shandong Province, People’s Republic of China *These authors contributed equally to this work 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. Keywords: lactoferrin-modified rotigotine nanoparticles, nose to brain, drug biodistribution, pharmacodynamics, neuroprotective effects, Parkinson’s disease
format	article
author	Yan X Xu L Bi C Duan D Chu L Yu X Wu Z Wang A Sun K
author_facet	Yan X Xu L Bi C Duan D Chu L Yu X Wu Z Wang A Sun K
author_sort	Yan X
title	Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects
title_short	Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects
title_full	Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects
title_fullStr	Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects
title_full_unstemmed	Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects
title_sort	lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: lesa-ms/ms-based drug biodistribution, pharmacodynamics, and neuroprotective effects
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/0632cb91d97a4d2cbb5c29aab52f0d36
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Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects

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