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Cited by 74Nanoparticle-Based Drug DeliveryAlzheimer's disease research and treatmentsAdvanced Drug Delivery Systems

Functionalization strategies of polymeric nanoparticles for drug delivery in Alzheimer’s disease: Current trends and future perspectives

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La Barbera, Livia, Mauri, Emanuele, D’Amelio, Marcello, Gori, Manuele·2022·Frontiers in Neuroscience
DOI 10.3389/fnins.2022.939855PMC PMC9387393
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Abstract

Alzheimer’s disease (AD), the most common form of dementia, is a progressive and multifactorial neurodegenerative disorder whose primary causes are mostly unknown. Due to the increase in life expectancy of world population, including developing countries, AD, whose incidence rises dramatically with age, is at the forefront among neurodegenerative diseases. Moreover, a definitive cure is not yet within reach, imposing substantial medical and public health burdens at every latitude. Therefore, the effort to devise novel and effective therapeutic strategies is still of paramount importance. Genetic, functional, structural and biochemical studies all indicate that new and efficacious drug delivery strategies interfere at different levels with various cellular and molecular targets. Over the last few decades, therapeutic development of nanomedicine at preclinical stage has shown to progress at a fast pace, thus paving the way for its potential impact on human health in improving prevention, diagnosis, and treatment of age-related neurodegenerative disorders, including AD. Clinical translation of nano-based therapeutics, despite current limitations, may present important advantages and innovation to be exploited in the neuroscience field as well. In this state-of-the-art review article, we present the most promising applications of polymeric nanoparticle-mediated drug delivery for bypassing the blood-brain barrier of AD preclinical models and boost pharmacological safety and efficacy. In particular, novel strategic chemical functionalization of polymeric nanocarriers that could be successfully employed for treating AD are thoroughly described. Emphasis is also placed on nanotheranostics as both potential therapeutic and diagnostic tool for targeted treatments. Our review highlights the emerging role of nanomedicine in the management of AD, providing the readers with an overview of the nanostrategies currently available to develop future therapeutic applications against this chronic neurodegenerative disease.

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  • In late-stage Alzheimer's disease, the blood-brain barrier becomes significantly disrupted due to vascular degeneration, chronic inflammation, and endothelial damage, leading to increased but non-specific permeability.

    “As AD progresses to its late stages, the effectiveness of nanoparticle-based therapies often diminishes due to the increased disruption of the BBB [148].”

    From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [148]

    In “The blood-brain barrier obstacle > Neurons” (page unavailable), the paper says that even a disrupted, more permeable BBB can challenge brain-targeted drug delivery and that therapeutic permeability and distribution across the AD BBB can be reduced. It does not establish that disruption increases specifically in late-stage AD or that nanoparticle therapies often become less effective as AD progresses; it also describes neuroinflammation as a consequence of BBB damage, not a stated cause. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
La Barbera, L., Mauri, E., D’Amelio, M., & Gori, M.
Affiliations
Università Campus Bio-Medico (IT)
Corresponding author
Gori, Manuele
ORCID
Venue
Frontiers in Neuroscience
Publisher
Frontiers Media SA
Published
2022-08-04
Volume
16
Pages
939855-939855
ISSN
1662-453X (ISSN-L)
DOI
10.3389/fnins.2022.939855
PMC
PMC9387393
OpenAlex
W4289781088
Cited by
74
References
45
Citations by year
2026: 15 · 2025: 23 · 2024: 21 · 2023: 11 · 2022: 4
FWCI
1.01
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Virtual Community of Pathological Anatomy (University of Castilla La Mancha) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Alzheimer's Association (AARG-21-851219, AARG-18-566270, AARG-21-)
  • Ministero della Salute (RF-2018-12365527, RF-2018)
  • Università Campus Bio-Medico di Roma
  • Fondazione Roma
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
Keywords
Alzheimer's disease, polymeric nanoparticles, drug delivery, blood-brain barrier, nanomedicine, nanotheranostics, neurodegenerative diseases, targeted drug delivery, clinical translation

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