Cited by 305Nanoparticle-Based Drug DeliveryAdvanced Drug Delivery SystemsBarrier Structure and Function Studies

The DOI matches its Crossref record; 239 of the 266 references it cites were found in a registry or an index; none of the 216 sources its claims cite is checked for support yet.

Nanotechnology: A Promising Approach for Delivery of Neuroprotective Drugs

Open access
Naqvi, Saba, Panghal, Archna, Flora, S. J. S.·2020·Frontiers in Neuroscience

Abstract

Central nervous system (CNS) disorders especially neurodegenerative disorders are the major challenge for public health and demand the great attention of researchers to protect people against them. In past few decades, different treatment strategies have been adopted, but their therapeutic efficacy are not enough and have only shown partial mitigation of symptoms. Blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BSCFB) guard the CNS from harmful substances and pose as the major challenges in delivering drugs into CNS for treatment of CNS complications such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), stroke, epilepsy, brain tumors, multiple sclerosis (MS), and encephalitis, etc. Nanotechnology has come out as an exciting and promising new platform of treating neurological disorders and has shown great potential to overcome problems related to the conventional treatment approaches. Molecules can be nanoengineered to carry out multiple specific functions such as to cross the BBB, target specific cell or signaling pathway, respond to endogenous stimuli, and act as a vehicle for gene delivery, support nerve regeneration and cell survival. In present review, the role of nanocarrier systems such as liposomes, micelles, solid lipid nanoparticles (SLNPs), dendrimers, and nanoemulsions for delivery of various neurotherapeutic agents has been discussed, besides this, their mechanism of action, and nanoformulation of different neuroprotective agents like curcumin, edaravone, nerve growth factors in CNS disorders like Alzheimer's, Parkinsonism, epilepsy, stroke, and brain tumors has been reviewed.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This narrative review argues that nanotechnology-based carriers—liposomes, micelles, solid lipid nanoparticles, polymeric nanoparticles, dendrimers, and nanoemulsions—can help overcome the blood-brain barrier and deliver neuroprotective agents for CNS disorders. It surveys preclinical and clinical examples across Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, multiple sclerosis, brain tumors, epilepsy, and stroke, while emphasizing unresolved toxicity and translation barriers.

Key findings

  • Nanocarriers are proposed to cross the BBB/BCSFB via mechanisms including endocytosis/transcytosis, P-gp efflux inhibition, tight-junction permeation, and surfactant-mediated membrane effects; the review cites nanocarrier size ranges such as micelles 10–100 nm, polymeric nanoparticles 10–100 nm, liposomes 10–1000 nm depending on type, and nanoemulsions 100–500 nm.
  • Disease-specific applications include curcumin nanoformulations for AD/PD/HD/stroke, NGF-loaded nanoparticles, edaravone lipid nanosystems, and nanocarriers for brain tumors and epilepsy; for stroke, the review states ischemic stroke contributes 87% of total stroke and hemorrhagic stroke 13% (10% intracerebral, 3% hemorrhagic).
  • Reported quantitative examples include NanoCurc at 25 mg/kg intraperitoneally twice daily in athymic mice, curcumin-loaded polysorbate 80-modified cerasomes at 15 mg curcumin/kg in a PD mouse model, xenon-loaded liposomes at 7–14 mg/kg reducing infarct size in a rat stroke model, and nitrendipine-associated dementia reduction up to 50% over 2 years in HD.
  • The global burden context cited is that in 2016 neurological disorders were the leading cause of DALYs [276 million (95% UI 247–308)] and the second leading cause of deaths [9.0 million (8.8–9.4)].

Methods

  • Narrative review; no primary experiments or systematic review/meta-analysis are described.
  • Synthesizes published literature on nanocarrier systems for CNS drug delivery, including tables of FDA-approved nanoformulated drugs, pharmacokinetic/biopharmaceutical properties, safety profiles, and disease-specific applications.
  • Main analysis is descriptive: compares nanocarrier types, proposed mechanisms of BBB crossing, and preclinical/clinical outcomes for neuroprotective agents such as curcumin, nerve growth factors, and edaravone.

Limitations

  • Stated: insufficient data exist to prove nanomedicines are better than conventional neurotherapeutics; nanocarriers may cause oxidative stress, amino acid disturbance, BBB disruption, neuroinflammation, excitotoxicity, DNA damage, and allergic responses.
  • Stated: clinical translation is limited by unclear fate of nanocarriers, systemic toxicity, biocompatibility, RES elimination, aggregation, limited drug loading, and high clearance; more toxicology, mechanism, pharmacokinetic, and non-invasive route studies are needed.
  • Evident: as a narrative review, it lacks a systematic search strategy or formal quality assessment and relies heavily on cited preclinical studies, so efficacy and safety claims are not independently validated by primary data in this paper.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3389/fnins.2020.00494

Cites

239 of 239 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Figures

FIGURE 1 Schematic presentation of various transportation pathways across BBB.
FIGURE 1 Schematic presentation of various transportation pathways across BBB.CC BY · PubMed Central
FIGURE 2 Nanotechnology-based various CNS delivery systems.
FIGURE 2 Nanotechnology-based various CNS delivery systems.CC BY · PubMed Central
FIGURE 3 Mechanism of nanotherapeutics, such as methotrexate and doxorubicin, delivery by dendrimers for brain tumor. Reproduced with permission from Xu et al. (2013). Copyright @ 2014, American Chemical Society.
FIGURE 3 Mechanism of nanotherapeutics, such as methotrexate and doxorubicin, delivery by dendrimers for brain tumor. Reproduced with permission from Xu et al. (2013). Copyright @ 2014, American Chemical Society.CC BY · PubMed Central
FIGURE 4 In vivo cellular localization of Cy5-D-mino. The endotoxin kits with Cerebral Palsy (n = 3) received Cy5-Dmino (55 mg/kg, i.v) on Post Natal Day 1 and sacrificed 24 h post-injection. Brain slices contain Cy5-D-mino (magenta) were co-stained with GFAP (astrocyte marker, green)/IBA1 (microglial marker, red)/DAPI (blue). Cy5-D-mino is mainly co-localized with activated microglia at the corpus callosum and angle of lateral ventricle. The images on the right panels are the higher magnification of the region of interest marked with the boxes on the left panels. Reproduced with permission from Sharma et al. (2017). Copyright @ 2017, American Chemical Society.
FIGURE 4 In vivo cellular localization of Cy5-D-mino. The endotoxin kits with Cerebral Palsy (n = 3) received Cy5-Dmino (55 mg/kg, i.v) on Post Natal Day 1 and sacrificed 24 h post-injection. Brain slices contain Cy5-D-mino (magenta) were co-stained with GFAP (astrocyte marker, green)/IBA1 (microglial marker, red)/DAPI (blue). Cy5-D-mino is mainly co-localized with activated microglia at the corpus callosum and angle of lateral ventricle. The images on the right panels are the higher magnification of the region of interest marked with the boxes on the left panels. Reproduced with permission from Sharma et al. (2017). Copyright @ 2017, American Chemical Society.CC BY · PubMed Central
FIGURE 5 Schematic representation of nanotechnology-based therapy for CNS disorders.
FIGURE 5 Schematic representation of nanotechnology-based therapy for CNS disorders.CC BY · PubMed Central
FIGURE 6 Various challenges for the nanotechnology-based drug delivery.
FIGURE 6 Various challenges for the nanotechnology-based drug delivery.CC BY · PubMed Central

Verification

Claims the paper makes

174 Not checked yet · 20 Own interpretation · 20 No basis given

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  • It may state two separate claims as one. 111
  • Probably not a substantial claim. 39
  • The quote only partly states this claim. 2
131 of 131
  • The paper relies on this without support.

    Results from preclinical models (mice, cell lines) are predictive of therapeutic outcomes in humans for CNS nanomedicines.

    “In mice, the intravenous administration of these modified micelles after loading with a fluorescent dye or neuroleptic drug haloperidol, resulted in improved delivery of the fluorescent dye to the brain and drastic increase in the neuroleptic effect of haloperidol (Kabanov et al., 1989).”
  • The paper relies on this without support.

    Conventional treatment approaches cannot completely treat Alzheimer disease, and orally administered drugs such as tacrine and rivastigmine are unable to treat the disease.

    “The conventional treatment approaches are not able for complete treatment of disease, thus the inability of orally administered drugs such as tacrine, rivastigmine, etc. to treat the disease, opens the door for the application of nanotechnology for AD treatment.”
  • The paper relies on this without support.

    Current medication treatments for Parkinson disease do not cure nor alleviate progression, and available drugs cannot cross the blood-brain barrier.

    “The current medication treatments available for PD do not cure nor alleviate the progression of the disease but aim to provide the symptomatic relief to the patients, and beside this, the inability of available drugs to cross BBB is another challenge for treating PD.”
  • The paper relies on this without support.

    Symptomatic and protective treatment strategies are available for Huntington disease but none are efficacious to completely cure the disease.

    “Symptomatic and protective treatment strategies are available for HD but none of them are efficacious to completely cure the disease.”
  • The paper relies on this without support.

    Current treatment methods for epilepsy are almost failures due to hurdles such as inability of drugs to cross the blood-brain barrier, drug resistance, and recurrence after drug discontinuation.

    “The current treatment methods, having the aim of diminishing the seizure frequency and severity while producing the minimum toxic effects to the brain and other tissues of the body, are almost failures due to various hurdles, such as the inability of drugs to cross BBB, drug resistance and recurrence of disease after drug discontinuation.”
  • The paper relies on this without support.

    Stroke is among the principal causes of mortality and morbidity due to challenges in drug treatment, demanding development of new therapeutic approaches.

    “It is among the principal cause of mortality and morbidity, regardless of the availability of a number of treatment approaches, due to various challenges in drug treatment, which demands the development of new therapeutic approaches.”
  • The paper relies on this without support.

    NGFs are needed for development and phenotype maintenance of neurons in the peripheral nervous system and for functional integrity of neurons in the CNS, and have therapeutic potential for various CNS disorders.

    “Various growth factors among which, Nerve growth factors (NGFs) are most essential, are needed for the development and phenotype maintenance of neurons in the peripheral nervous system and for the functional integrity of neurons in the CNS. NGFs have great therapeutic potential for various CNS disorders (Table 6).”
  • The paper relies on this without support.

    VEGF participates in post-ischemic brain repair via promoting neurogenesis and cerebral angiogenesis and is potentially useful to attenuate ischemic brain injury.

    “Vascular endothelial growth factor (VEGF) was considered as a potentially useful therapeutic agent to attenuate ischemic brain injury, as it has been shown to participate in the process of post-ischemic brain repair via promoting neurogenesis and cerebral angiogenesis.”
  • The paper relies on this without support.

    No oral formulation of edaravone is currently available; only an intravenous liquid formulation is commercially available.

    “No oral formulation of the EDR is currently available in the market and liquid formulation for the purpose of intravenous infusion is the only commercially available formulation.”
  • The paper relies on this without support.

    The blood-brain barrier and blood-cerebrospinal fluid barrier are the main physiological barriers and a bottleneck for successful treatment of CNS disorders and brain tumors.

    “BBB and BCSFB is the main physiological barrier which possess big bottleneck for the successful treatment of CNS disorders and brain tumors, complex anatomical structure, unique microenvironment, and their selectivity toward any foreign compound including drug is treated as a biggest challenge toward CNS drug delivery.”
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Citations

Cites

1 retracted

Show all 266 references

Research works printed but not linked: 5

  1. 2017, FDA Approved Drugs.
  2. 2017, Our Product: Zilretta (triamcinolone acetonide extended. (release)Formulation).
  3. 2017, Novel drug approvals for 2017.
  4. Özdemir, 2017, Nanotechnology Methods for Neurological Diseases and Brain Tumors: Drug Delivery Across the Blood–Brain Barrier.
  5. Xu, 2014, Dendrimer advances for the central nervous system delivery of therapeutics., ACS Chem. Neurosci., 5, 2, 10.1021/cn400182z · DOI

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Metadata

Authors
Naqvi, S., Panghal, A., & Flora, S. J. S.
Affiliations
National Institute of Pharmaceutical Education and Research (IN)
Corresponding author
  • Naqvi, Saba
  • Flora, S. J. S.
Venue
Frontiers in Neuroscience
Published
2020-06-09
Volume
14
Pages
494-494
ISSN
1662-453X (ISSN-L)
OpenAlex
W3034784818
Cited by
305
References
266
Citations by year
2026: 24 · 2025: 61 · 2024: 66 · 2023: 61 · 2022: 54 · 2021: 32 · 2020: 7
FWCI
2.58
Type
journal article
Language
en
Open access
Locations
  • Frontiers in Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
All India Council for Technical Education
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
nanotechnology, drug delivery, neuroprotection, blood-brain barrier, blood-CSF barrier, nanocarriers, liposomes, micelles, solid lipid nanoparticles, dendrimers, nanoemulsions, neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, epilepsy, stroke, brain tumors, curcumin, edaravone, nerve growth factor, gene delivery, nerve regeneration

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