Nanoparticle Brain Delivery: A Guide to Verification Methods

Yokel, Robert A.

doi:10.2217/nnm-2019-0169

Cited by 27 publications

(32 citation statements)

References 139 publications

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“…Even if nanoparticles reach the cerebrospinal fluid, they still cannot directly access the brain parenchyma because of the ependymal/glial barrier. Only a tiny proportion of drugs injected into the blood or ventricles normally reaches the brain parenchyma; for this reason, it is essential when quantitating transport to verify exactly where in the brain the drug/treatment is located [ 19 ].…”

Section: Barriers For Nanoparticle Transport Into the Cnsmentioning

confidence: 99%

Nanocarriers for Delivery of Oligonucleotides to the CNS

Male

Gromnicova

2022

IJMS

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Nanoparticles with oligonucleotides bound to the outside or incorporated into the matrix can be used for gene editing or to modulate gene expression in the CNS. These nanocarriers are usually optimised for transfection of neurons or glia. They can also facilitate transcytosis across the brain endothelium to circumvent the blood-brain barrier. This review examines the different formulations of nanocarriers and their oligonucleotide cargoes, in relation to their ability to enter the brain and modulate gene expression or disease. The size of the nanocarrier is critical in determining the rate of clearance from the plasma as well as the intracellular routes of endothelial transcytosis. The surface charge is important in determining how it interacts with the endothelium and the target cell. The structure of the oligonucleotide affects its stability and rate of degradation, while the chemical formulation of the nanocarrier primarily controls the location and rate of cargo release. Due to the major anatomical differences between humans and animal models of disease, successful gene therapy with oligonucleotides in humans has required intrathecal injection. In animal models, some progress has been made with intraventricular or intravenous injection of oligonucleotides on nanocarriers. However, getting significant amounts of nanocarriers across the blood-brain barrier in humans will likely require targeting endothelial solute carriers or vesicular transport systems.

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Section: Barriers For Nanoparticle Transport Into the Cnsmentioning

confidence: 99%

Nanocarriers for Delivery of Oligonucleotides to the CNS

Male

Gromnicova

2022

IJMS

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“…Few studies demonstrated nanoparticle entry into brain parenchyma after i.n. administration that met established criteria (Yokel, 2020). Cited studies that gave the nanoparticle intranasally showed evidence that chitosan increased brain or CSF uptake from the nasal cavity, but none showed intact nanoparticle translocation into brain parenchyma (Casettari & Illum, 2014).…”

Section: Demonstration Of Brain Parenchyma Nanomedicine Deliverymentioning

confidence: 99%

Direct nose to the brain nanomedicine delivery presents a formidable challenge

Yokel

2021

WIREs Nanomed Nanobiotechnol

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This advanced review describes the anatomical and physiological barriers and mechanisms impacting nanomedicine translocation from the nasal cavity directly to the brain. There are significant physiological and anatomical differences in the nasal cavity, olfactory area, and airflow reaching the olfactory epithelium between humans and experimentally studied species that should be considered when extrapolating experimental results to humans. Mucus, transporters, and tight junction proteins present barriers to material translocation across the olfactory epithelium. Uptake of nanoparticles through the olfactory mucosa and translocation to the brain can be intracellular via cranial nerves (intraneuronal) or other cells of the olfactory epithelium, or extracellular along cranial nerve pathways (perineural) and surrounding blood vessels (perivascular, the glymphatic system). Transport rates vary greatly among the nose to brain pathways. Nanomedicine physicochemical properties (size, surface charge, surface coating, and particle stability) can affect uptake efficiency, which is usually less than 5%. Incorporation of therapeutic agents in nanoparticles has been shown to produce pharmacokinetic and pharmacodynamic benefits. Assessment of adverse effects has included olfactory mucosa toxicity, ciliotoxicity, and olfactory bulb and brain neurotoxicity. The results have generally suggested the investigated nanomedicines do not present significant toxicity. Research needs to advance the understanding of nanomedicine translocation and its drug cargo after intranasal administration is presented. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials

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“…The BMECs present a single layer of compact, almost nonfenestrated endothelial cells, sealed together by tight junctions. The efflux transporters of BMECs prevent the entry of arbitrary substances, ions and enzymes, in the brain parenchyma while the influx transporters allow the inward movement of essential nutrients and necessary factors to the brain cells [21]. The BBB, thus, competently sustains the brain homeostasis and functional and architectural integrity.…”

Section: Treatmentmentioning

confidence: 99%

“…For greater access to the CNS of NPs, the nasal route of drug delivery has become popular as of late. The roof of the nasal palate is perhaps the sole region of the body where direct uptake of NP into the CNS, bypassing the BBB, is a possibility [21]. It is also advantageous that TBI often results in leaky BBB making NP drug delivery feasible.…”

Section: Nanomedicine For Tbimentioning

confidence: 99%

Traumatic brain injury: Future application of nanomedicine

Khanam¹,

Nath²

2021

GSC Adv. Res. Rev.

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Traumatic brain injury (TBI) is currently a rising player in the cause of disability and neurological dysfunction worldwide. TBI is a common occurrence in the military and extreme activities, sports arena and accidents. Severe TBI can be fatal but mild TBI persists and progressively deteriorates brain homeostasis and physiology. Apart from the physical disabilities, psychological complexities arise in people with mild TBI. Despite the seriousness of this hazard, treatments for TBI are not adequate, mostly due to the brain being involved. Nanoparticle (NP) therapy seems to be an effective alternative to combat TBI. This review outlines the state of TBI and describes the probable medical support that nanomedicine can provide.

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Nanoparticle Brain Delivery: A Guide to Verification Methods

Cited by 27 publications

References 139 publications

Nanocarriers for Delivery of Oligonucleotides to the CNS

Nanocarriers for Delivery of Oligonucleotides to the CNS

Direct nose to the brain nanomedicine delivery presents a formidable challenge

Traumatic brain injury: Future application of nanomedicine

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