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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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Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects
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Journal Article
Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects
2018
Overview
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.
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.
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 (
<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.
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.
Publisher
Dove Medical Press Limited,Taylor & Francis Ltd,Dove Medical Press
Subject
/ Analysis
/ Animals
/ Dopamine
/ Dopamine Agonists - administration & dosage
/ Dopamine Agonists - pharmacokinetics
/ Dopamine Agonists - pharmacology
/ Drug Carriers - administration & dosage
/ Drug Delivery Systems - methods
/ Drugs
/ L-dopa
/ lactoferrin-modified rotigotine nanoparticles
/ Male
/ Nanoparticles - administration & dosage
/ Neuroprotective Agents - administration & dosage
/ Neuroprotective Agents - pharmacokinetics
/ Neuroprotective Agents - pharmacology
/ Parkinson Disease - drug therapy
/ Phenols (Class of compounds)
/ Studies
/ Tetrahydronaphthalenes - administration & dosage
/ Tetrahydronaphthalenes - pharmacokinetics
/ Thiophenes - administration & dosage
/ Thiophenes - pharmacokinetics
/ Tyrosine
