Novel Therapeutic Approaches for the Treatment of Neurodegenerative Diseases

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: 20 July 2024 | Viewed by 1464

Special Issue Editors


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Guest Editor
Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy
Interests: Alpha-synuclein; Synapsin III; Parkinson’s disease; Dopaminergic synapses; protein aggregation; fibrillation; small molecules

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Guest Editor
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Luigi Mangiagalli, 25, 20133 Milan, Italy
Interests: drug discovery; medicinal chemistry, structure activity relationship; development of novel antimicrobials; FtsZ inhibitors; RnpA inhibitors; inhibition of bacterial cellular division process
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Special Issue Information

Dear Colleagues,

Neurodegenerative diseases are a heterogeneous group of disorders characterized by the progressive loss of neurons in the central or peripheral nervous system and can present different symptomatologic manifestations mainly affecting cognition and motility. Among them, the most common age-associated disorders are Alzheimer’s disease and Parkinson’s disease, followed by conditions with lower incidence such as Frontotemporal Lobar degeneration (FTLD) syndromes, Lewy Body dementia, Amyotrophic Lateral Sclerosis, Multiple system Atrophy, Huntington’s disease. A main common neuropathological feature of most of these syndromes is the progressive deposition of pathological protein aggregates that is considered to play a main causative role in onset and worsening of these disorders.

In the last two decades, the number of people living with neurodegenerative disorders has raised due to increased aging of world population, and their social and economic burden has become a major health issue. This notwithstanding, despite the great efforts dedicated to the identification new therapeutic targets and development of innovative disease-modifying agents, we still miss effective approaches able to halt or delay symptom progression and neurodegeneration in the brain of patients affected by these highly disabling conditions.

The aim of this Special Issue is to collect the latest research on novel therapeutic targets, as well as innovative deliveries or formulations, for the design and pharmacological characterization of disease-modifying agents, counteracting neuronal loss, exerting neuroprotection or reducing pathological protein aggregates in neurodegenerative diseases.

Dr. Francesca Longhena
Dr. Valentina Straniero
Guest Editors

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Keywords

  • Alzheimer’s disease
  • Parkinson’s disease
  • Huntington’s disease
  • frontotemporal lobar degeneration syndromes
  • amyotrophic lateral sclerosis
  • multple system Atrophy
  • lewy body dementia
  • synucleinopathies
  • Pick’s disease
  • corticobasal degeneration
  • protein aggregates
  • disease-modifying therapies
  • treatment
  • neuroprotection

Published Papers (1 paper)

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19 pages, 2205 KiB  
Systematic Review
Navigating the Nose-to-Brain Route: A Systematic Review on Lipid-Based Nanocarriers for Central Nervous System Disorders
by Edoardo Agosti, Marco Zeppieri, Sara Antonietti, Luigi Battaglia, Tamara Ius, Caterina Gagliano, Marco Maria Fontanella and Pier Paolo Panciani
Pharmaceutics 2024, 16(3), 329; https://doi.org/10.3390/pharmaceutics16030329 - 27 Feb 2024
Viewed by 1063
Abstract
Background: The blood–brain barrier (BBB) regulates brain substance entry, posing challenges for treating brain diseases. Traditional methods face limitations, leading to the exploration of non-invasive intranasal drug delivery. This approach exploits the direct nose-to-brain connection, overcoming BBB restrictions. Intranasal delivery enhances drug bioavailability, [...] Read more.
Background: The blood–brain barrier (BBB) regulates brain substance entry, posing challenges for treating brain diseases. Traditional methods face limitations, leading to the exploration of non-invasive intranasal drug delivery. This approach exploits the direct nose-to-brain connection, overcoming BBB restrictions. Intranasal delivery enhances drug bioavailability, reduces dosage, and minimizes systemic side effects. Notably, lipid nanoparticles, such as solid lipid nanoparticles and nanostructured lipid carriers, offer advantages like improved stability and controlled release. Their nanoscale size facilitates efficient drug loading, enhancing solubility and bioavailability. Tailored lipid compositions enable optimal drug release, which is crucial for chronic brain diseases. This review assesses lipid nanoparticles in treating neuro-oncological and neurodegenerative conditions, providing insights for effective nose-to-brain drug delivery. Methods: A systematic search was conducted across major medical databases (PubMed, Ovid MEDLINE, and Scopus) up to 6 January 2024. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to “lipid nanoparticles”, “intranasal administration”, “neuro-oncological diseases”, and “neurodegenerative disorders”. This review consists of studies in vitro, in vivo, or ex vivo on the intranasal administration of lipid-based nanocarriers for the treatment of brain diseases. Results: Out of the initial 891 papers identified, 26 articles met the eligibility criteria after a rigorous analysis. The exclusion of 360 articles was due to reasons such as irrelevance, non-reporting selected outcomes, the article being a systematic literature review or meta-analysis, and lack of method/results details. This systematic literature review, focusing on nose-to-brain drug delivery via lipid-based nanocarriers for neuro-oncological, neurodegenerative, and other brain diseases, encompassed 60 studies. A temporal distribution analysis indicated a peak in research interest between 2018 and 2020 (28.3%), with a steady increase over time. Regarding drug categories, Alzheimer’s disease was prominent (26.7%), followed by antiblastic drugs (25.0%). Among the 65 drugs investigated, Rivastigmine, Doxorubicin, and Carmustine were the most studied (5.0%), showcasing a diverse approach to neurological disorders. Notably, solid lipid nanoparticles (SLNs) were predominant (65.0%), followed by nanostructured lipid carriers (NLCs) (28.3%), highlighting their efficacy in intranasal drug delivery. Various lipids were employed, with glyceryl monostearate being prominent (20.0%), indicating preferences in formulation. Performance assessment assays were balanced, with in vivo studies taking precedence (43.3%), emphasizing the translation of findings to complex biological systems for potential clinical applications. Conclusions: This systematic review reveals the transformative potential of intranasal lipid nanoparticles in treating brain diseases, overcoming the BBB. Positive outcomes highlight the effectiveness of SLNs and NLCs, which are promising new approaches for ailments from AD to stroke and gliomas. While celebrating progress, addressing challenges like nanoparticle toxicity is also crucial. Full article
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