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Cited by 350Barrier Structure and Function StudiesDrug Transport and Resistance MechanismsNanoparticle-Based Drug Delivery

Current approaches to enhance CNS delivery of drugs across the brain barriers

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Lu, Cui-Tao, Zhao, Ying-Zheng, Wong, Ho Lun, Cai, Jun, Peng, Lei, Tian, Xin-Qiao·2014·International Journal of Nanomedicine
DOI 10.2147/ijn.s61288PMC PMC4026551
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Abstract

Abstract: Although many agents have therapeutic potentials for central nervous system (CNS) diseases, few of these agents have been clinically used because of the brain barriers. As the protective barrier of the CNS, the blood–brain barrier and the blood–cerebrospinal fluid barrier maintain the brain microenvironment, neuronal activity, and proper functioning of the CNS. Different strategies for efficient CNS delivery have been studied. This article reviews the current approaches to open or facilitate penetration across these barriers for enhanced drug delivery to the CNS. These approaches are summarized into three broad categories: noninvasive, invasive, and miscellaneous techniques. The progresses made using these approaches are reviewed, and the associated mechanisms and problems are discussed. Keywords: drug delivery system, blood–brain barrier (BBB), central nervous system, brain-targeted therapy, cerebrospinal fluid (CSF) A Letter to the editor has been published about this paper

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  • Direct CNS administration is limited by diffusion distance and rapid efflux of drugs out of the CNS within hours.

    “However, direct CNS administration is invasive, which may cause infection and tissue damage, and is also limited by diffusion distance and rapid efflux of drugs out of the CNS within hours (8–10).”

    From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [10]

    The Invasive techniques sections report inadequate drug distribution after direct delivery and poor penetration beyond an intracerebral implant site, supporting a distribution limitation. They do not state that drugs rapidly leave the CNS within hours. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Direct CNS administration is invasive and may cause infection and tissue damage.

    “However, direct CNS administration is invasive, which may cause infection and tissue damage, and is also limited by diffusion distance and rapid efflux of drugs out of the CNS within hours (8–10).”

    From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [10]

    The Invasive techniques sections describe direct CNS delivery, list CNS infection as a disadvantage of local delivery, and call intracerebral implantation highly traumatic. They also report inadequate drug distribution and poor penetration, but do not substantiate the citing sentence’s claim that drugs rapidly leave the CNS within hours. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Compared to systemic delivery, the intra-CSF route performs a more invasive procedure, but attenuates exposure to pre-existing neutralizing antibodies from the vascular system and avoids the risk of liver toxicity after intravenous administration of high doses.

    “While comparing to systemic delivery, intra-CSF route performs in a more invasive procedure, but on the other hand, attenuates the exposure to pre-existing neutralizing antibodies from vascular system and avoids the risk of liver toxicity after intravenous administration of high doses [87].”

    From Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside (2024) · cites this paper as [87]

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

    Experimental — accuracy not yet measured

  • Efficient delivery and targeting of molecules of interest to the brain is a challenge in Alzheimer's disease treatments because of the protective barriers of the central nervous system.

    “Another challenge in AD treatments is the efficient delivery and targeting of molecules of interest to the brain due to the protective barriers of the central nervous system [27,28].”

    From Alzheimer's Disease: Treatment Strategies and Their Limitations. (2022) · cites this paper as [27]

  • The blood-brain barrier protects the central nervous system from potential neurotoxins, toxic organisms, and chemical substances in the blood, but also limits its accessibility for many therapeutic drug molecules.

    “BBB protects the CNS from potential neurotoxins, toxic organisms, and chemical substances in the blood, but that also limits its accessibility for many therapeutic drug molecules [27].”

    From Alzheimer's Disease: Treatment Strategies and Their Limitations. (2022) · cites this paper as [27]

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Authors
Lu, C.-T., Zhao, Y.-Z., Wong, H. L., Cai, J., Peng, L., & Tian, X.-Q.
Affiliations
  • Wenzhou Medical University (CN)
  • Temple University (US)
  • University of Louisville (US)
  • Hainan Medical College Hospital (CN)
Corresponding author
Zhao, Ying-Zheng
ORCID
Venue
International Journal of Nanomedicine
Publisher
Informa UK Limited
Published
2014-05
Volume
9
Pages
2241
ISSN
  • 1176-9114 (ISSN-L)
  • 1178-2013
DOI
10.2147/ijn.s61288
PMC
PMC4026551
OpenAlex
W2005218288
Cited by
350
References
149
Citations by year
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FWCI
1.13
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Nanomedicine (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
Funders
Natural Science Foundation of Zhejiang Province (LY12H30003, LY12H18001, LY12H03001, LQ12H30001)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords
brain drug delivery, blood-brain barrier, blood-CSF barrier, blood-brain barrier disruption, non-invasive drug delivery, central nervous system disorders
MeSH terms
Animals, Blood-Brain Barrier, Central Nervous System Agents, Humans, Drug Design, Nanocapsules, Molecular Targeted Therapy

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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