Levodopa-loaded nanoparticles for the treatment of Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) resulting in dopamine (DA) deficiency, which manifests itself in motor symptoms including tremors, rigidity and bradykinesia. Current PD tr...

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Bibliographic Details
Published in:Journal of controlled release 2023-08, Vol.360, p.212-224
Main Authors: van Vliet, Emile F., Knol, Maarten J., Schiffelers, Raymond M., Caiazzo, Massimiliano, Fens, Marcel H.A.M.
Format: Article
Language:English
Subjects:
Blood-brain barrier
Drug delivery
Intranasal brain delivery
Lipid nanoparticles
Polymeric nanoparticles
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Summary:Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) resulting in dopamine (DA) deficiency, which manifests itself in motor symptoms including tremors, rigidity and bradykinesia. Current PD treatments aim at symptom reduction through oral delivery of levodopa (L-DOPA), a precursor of DA. However, L-DOPA delivery to the brain is inefficient and increased dosages are required as the disease progresses, resulting in serious side effects like dyskinesias. To improve PD treatment efficacy and to reduce side effects, recent research focuses on the encapsulation of L-DOPA into polymeric- and lipid-based nanoparticles (NPs). These formulations can protect L-DOPA from systemic decarboxylation into DA and improve L-DOPA delivery to the central nervous system. Additionally, NPs can be modified with proteins, peptides and antibodies specifically targeting the blood-brain barrier (BBB), thereby reducing required dosages and free systemic DA. Alternative delivery approaches for NP-encapsulated L-DOPA include intravenous (IV) administration, transdermal delivery using adhesive patches and direct intranasal administration, facilitating increased therapeutic DA concentrations in the brain. This review provides an overview of the recent advances for NP-mediated L-DOPA delivery to the brain, and debates challenges and future perspectives on the field. [Display omitted] •We review the current treatment for Parkinson's disease and its drawbacks.•We highlight employing different types of levodopa-loaded nanoparticles.•We discuss different administration routes for levodopa-loaded nanoparticles.
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2023.06.026