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Cited by 430Nanoparticle-Based Drug DeliveryBarrier Structure and Function StudiesAdvanced Drug Delivery Systems

Development of Polymeric Nanoparticles for Blood–Brain Barrier Transfer—Strategies and Challenges

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Zhang, Weisen, Mehta, Ami, Tong, Ziqiu, Esser, Lars, Voelcker, Nicolas H.·2021·Advanced Science
DOI 10.1002/advs.202003937PMC PMC8132167
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Abstract

Neurological disorders such as Alzheimer's disease, stroke, and brain cancers are difficult to treat with current drugs as their delivery efficacy to the brain is severely hampered by the presence of the blood–brain barrier (BBB). Drug delivery systems have been extensively explored in recent decades aiming to circumvent this barrier. In particular, polymeric nanoparticles have shown enormous potentials owing to their unique properties, such as high tunability, ease of synthesis, and control over drug release profile. However, careful analysis of their performance in effective drug transport across the BBB should be performed using clinically relevant testing models. In this review, polymeric nanoparticle systems for drug delivery to the central nervous system are discussed with an emphasis on the effects of particle size, shape, and surface modifications on BBB penetration. Moreover, the authors critically analyze the current in vitro and in vivo models used to evaluate BBB penetration efficacy, including the latest developments in the BBB‐on‐a‐chip models. Finally, the challenges and future perspectives for the development of polymeric nanoparticles to combat neurological disorders are discussed.

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  • In the context of Alzheimer's disease, synthetic polymers such as chitosan and poly(lactic-co-glycolic acid) (PLGA) are the most common choice for brain-targeting polymeric nanoparticles.

    “For brain targeting, systems based on natural, synthetic, and hybrid materials are frequently employed; however, in the context of AD, synthetic polymers such as chitosan and poly(lactic-co-glycolic acid) (PLGA) are the most common choice [81].”

    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 [81]

    In “Natural Polymeric Nanoparticles” (page unavailable), the paper explicitly classifies chitosan as a natural polymer, contrary to the claim that it is synthetic. “Synthetic Polymeric Nanoparticles” discusses PLGA formulations for crossing the blood–brain barrier, but does not establish that chitosan and PLGA are the most common choices for Alzheimer’s disease. (LLM, conf=0.87)

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  • Lipid-based nanoparticles are effective carriers for lipophilic drugs with potential in reducing Aβ plaques; polymeric nanoparticles are known for controlled and sustained drug release, suitable for managing Alzheimer's disease's chronic progression; inorganic nanoparticles are utilized in diagnostics, facilitating combined imaging and therapeutic functions.

    “Lipid-based NPs: Effective carriers for lipophilic drugs, with potential in reducing Aβ plaques [81].Polymeric NPs: Known for controlled and sustained drug release, suitable for managing AD's chronic progression [204].Inorganic NPs: Utilized in diagnostics, facilitating combined imaging and therapeutic functions, aiding in monitoring disease progression [81].”

    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 [81]

    Split into 3 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

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  • Scaling up production while maintaining consistent quality and performance poses significant hurdles.

    “Additionally, scaling up production while maintaining consistent quality and performance poses significant hurdles [81].”

    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 [81]

    The Current Research Challenges and Future Perspectives section discusses validation and regulatory hurdles for BBB testing models, not scaling up nanoparticle production. Searches for scale-up, large-scale manufacturing, batch-to-batch consistency, and quality control found no passage addressing whether production can maintain consistent quality and performance. Page numbers were unavailable in our copy. (LLM, conf=0.71)

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Authors
Zhang, W., Mehta, A., Tong, Z., Esser, L., & Voelcker, N. H.
Affiliations
  • Monash University (AU)
  • Indian Institute of Technology Bombay (IN)
  • Commonwealth Scientific and Industrial Research Organisation (AU)
Corresponding author
  • Esser, Lars
  • Voelcker, Nicolas H.
ORCID
Venue
Advanced Science
Publisher
Wiley
Published
2021-03-07
Volume
8
Issue
10
Pages
2003937-2003937
ISSN
2198-3844 (ISSN-L)
DOI
10.1002/advs.202003937
PMC
PMC8132167
OpenAlex
W3135720699
Cited by
430
References
18
Citations by year
2026: 53 · 2025: 124 · 2024: 102 · 2023: 90 · 2022: 51 · 2021: 10
FWCI
4.37
Type
journal article
Language
en
Open access
Licence
Locations
  • Advanced Science (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Australian Institute of Nuclear Science and Engineering
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
Keywords
polymeric nanoparticles, blood-brain barrier, blood-brain barrier penetration, brain drug delivery, particle size and shape effects, surface modification, neurological disorders, Alzheimer's disease, stroke, brain cancer
MeSH terms
Animals, Blood-Brain Barrier, Brain Neoplasms, Humans, Particle Size, Polymers, Drug Delivery Systems, Neurodegenerative Diseases, Nanoparticles

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