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Cited by 60Barrier Structure and Function StudiesAlzheimer's disease research and treatmentsDrug Transport and Resistance Mechanisms

Alzheimer’s disease and drug delivery across the blood–brain barrier: approaches and challenges

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Iqbal, Iram, Saqib, Fatima, Mubarak, Zobia, Latif, Muhammad Farhaj, Wahid, Muqeet, Nasir, Bushra, Shahzad, Hamna, Sharifi-Rad, Javad +1 more·2024·European Journal of Medical Research
DOI 10.1186/s40001-024-01915-3PMC PMC11161981
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Abstract

Alzheimer's disease (AD) is a diverse disease with a complex pathophysiology. The presence of extracellular β-amyloid deposition as neuritic plaques and intracellular accumulation of hyper-phosphorylated tau as neurofibrillary tangles remain the core neuropathologic criteria for diagnosing Alzheimer's disease. Nonetheless, several recent basic discoveries have revealed significant pathogenic roles for other essential cellular and molecular processes. Previously, there were not so many disease-modifying medications (DMT) available as drug distribution through the blood-brain barrier (BBB) is difficult due to its nature, especially drugs of polypeptides nature and proteins. Recently FDA has approved lecanemab as DMT for its proven efficacy. It is also complicated to deliver drugs for diseases like epilepsy or any brain tumor due to the limitations of the BBB. After the advancements in the drug delivery system, different techniques are used to transport the medication across the BBB. Other methods are used, like enhancement of brain blood vessel fluidity by liposomes, infusion of hyperosmotic solutions, and local intracerebral implants, but these are invasive approaches. Non-invasive approaches include the formulation of nanoparticles and their coating with polymers. This review article emphasizes all the above-mentioned techniques, procedures, and challenges to transporting medicines across the BBB. It summarizes the most recent literature dealing with drug delivery across the BBB.

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  • In early-stage Alzheimer's disease, the blood-brain barrier remains mostly intact with only minor changes in permeability, which facilitates nanoparticle crossing and delivery.

    “In the early stages of AD, the BBB remains mostly intact, with only minor changes in its permeability [82].”

    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 [82]

    The Blood–brain barrier (BBB) section describes BBB disruption as an initiating event in a proposed AD disease cascade and reports faster BBB breakdown in people with mild cognitive impairment or AD. That runs contrary to the cited sentence’s characterization of the early-stage barrier as mostly intact with only minor permeability changes. The paper discusses nanoparticle delivery elsewhere, but does not connect it to that early-stage characterization. (LLM, conf=0.78)

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  • Surfactants can enhance drug delivery across the blood-brain barrier by increasing the fluidity of the endothelial cell membrane.

    “The use of surfactants can enhance drug delivery across the BBB by increasing the fluidity of the endothelial cell membrane [82].”

    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 [82]

    The Polymer-based nanoparticles section says a surfactant may increase drug permeability across the BBB by solubilizing lipids in the endothelial cell membrane. It does not say the mechanism is increased membrane fluidity. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Nanoparticles may adversely affect the cerebral vasculature, potentially reducing endothelial permeability.

    “Nevertheless, NPs may adversely affect the cerebral vasculature, potentially reducing endothelial permeability.”

    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 [82]

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Authors
Iqbal, I., Saqib, F., Mubarak, Z., Latif, M. F., Wahid, M., Nasir, B., Shahzad, H., Sharifi-Rad, J., & Mubarak, M. S.
Affiliations
  • Bahauddin Zakariya University (PK)
  • University of the Punjab (PK)
  • University of Jordan (JO)
Corresponding author
  • Iqbal, Iram
  • Saqib, Fatima
  • Mubarak, Zobia
  • Latif, Muhammad Farhaj
  • Wahid, Muqeet
  • Nasir, Bushra
  • Shahzad, Hamna
  • Mubarak, Mohammad S.
ORCID
Venue
European Journal of Medical Research
Publisher
Springer Science and Business Media LLC
Published
2024-06-08
Volume
29
Issue
1
Pages
313-313
ISSN
  • 0949-2321 (ISSN-L)
  • 2047-783X
DOI
10.1186/s40001-024-01915-3
PMC
PMC11161981
OpenAlex
W4399465964
Cited by
60
References
138
Citations by year
2026: 24 · 2025: 30 · 2024: 6
FWCI
3.06
Type
journal article
Language
en
Open access
Licence
Locations
  • European journal of medical research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
Alzheimer's disease, blood-brain barrier, drug delivery, disease-modifying therapy, lecanemab, amyloid-beta, tau hyperphosphorylation, liposomes, hyperosmolar solutions, nanoparticles, polymer-coated nanoparticles, non-invasive drug delivery, epilepsy, brain tumors
MeSH terms
Alzheimer Disease, Animals, Biological Transport, Blood-Brain Barrier, Humans, Drug Delivery Systems

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