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Review
. 2021 Nov 8;13(11):1897.
doi: 10.3390/pharmaceutics13111897.

Nanoparticle-Guided Brain Drug Delivery: Expanding the Therapeutic Approach to Neurodegenerative Diseases

Claudia Riccardi  1 , Filomena Napolitano  2 , Daniela Montesarchio  1 , Simone Sampaolo  2 , Mariarosa Anna Beatrice Melone  2   3
Affiliations
Review

Nanoparticle-Guided Brain Drug Delivery: Expanding the Therapeutic Approach to Neurodegenerative Diseases

Claudia Riccardi et al. Pharmaceutics. .

Abstract

Neurodegenerative diseases (NDs) represent a heterogeneous group of aging-related disorders featured by progressive impairment of motor and/or cognitive functions, often accompanied by psychiatric disorders. NDs are denoted as 'protein misfolding' diseases or proteinopathies, and are classified according to their known genetic mechanisms and/or the main protein involved in disease onset and progression. Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD) are included under this nosographic umbrella, sharing histopathologically salient features, including deposition of insoluble proteins, activation of glial cells, loss of neuronal cells and synaptic connectivity. To date, there are no effective cures or disease-modifying therapies for these NDs. Several compounds have not shown efficacy in clinical trials, since they generally fail to cross the blood-brain barrier (BBB), a tightly packed layer of endothelial cells that greatly limits the brain internalization of endogenous substances. By engineering materials of a size usually within 1-100 nm, nanotechnology offers an alternative approach for promising and innovative therapeutic solutions in NDs. Nanoparticles can cross the BBB and release active molecules at target sites in the brain, minimizing side effects. This review focuses on the state-of-the-art of nanoengineered delivery systems for brain targeting in the treatment of AD, PD and HD.

Keywords: blood–brain barrier; brain targeting; drug delivery systems; nanoformulations; neurodegenerative diseases; nose-to-brain delivery; targeted delivery.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Molecular structures of main anti-AD drugs.
Figure 2
Figure 2
Molecular structures of main anti-PD drugs.
Figure 3
Figure 3
Molecular structures of main anti-HD drugs.
Figure 4
Figure 4
Main causes, symptoms and conventional treatments for the main three neurodegenerative disorders here described.
Figure 5
Figure 5
Molecular structures of polyphenol compounds here described.
Figure 6
Figure 6
Schematic representation of the main methods for BBB crossing. AMT: adsorption-mediated transcytosis, RMT: receptor-mediated transcytosis.
Figure 7
Figure 7
Main nanosystems exploited to delivery drugs to BBB in the treatment of neurodegenerative diseases.
See this image and copyright information in PMC

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