Overcoming Blood-Brain Barrier Resistance: Implications for Extracellular Vesicle-Mediated Drug Brain Delivery

Dardet, Jean Paul; Serrano, Nelson; András, Ibolya E.; Toborek, Michał

doi:10.3389/fddev.2022.855017

Cited by 8 publications

(5 citation statements)

References 119 publications

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“…The integrated defence systems of the BBB impose a major challenge for effective drug delivery and the treatment of many brain diseases. Over the past decade, multiple strategies to improve drug delivery across the BBB have focused on non-invasive techniques [ 59 ].…”

Section: Introductionmentioning

confidence: 99%

Exploring the Potential of Cannabinoid Nanodelivery Systems for CNS Disorders

et al. 2023

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Cannabinoids have a major therapeutic value in a variety of disorders. The concepts of cannabinoids are difficult to develop, but they can be used and are advantageous for a number of diseases that are not sufficiently managed by existing treatments. Nanoconjugation and encapsulation techniques have been shown to be effective in improving the delivery and the therapeutic effectiveness of drugs that are poorly soluble in water. Because the bioavailability of cannabinoids is low, the challenge is to explore different administration methods to improve their effectiveness. Because cannabinoids cross the blood-brain-barrier (BBB), they modify the negative effects of inflammatory processes on the BBB and may be a key factor in the improvement of BBB function after ischemic disease or other conditions. This review discusses various types of cannabinoid administration, as well as nanotechnologies used to improve the bioavailability of these compounds in CNS diseases.

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Section: Introductionmentioning

confidence: 99%

Exploring the Potential of Cannabinoid Nanodelivery Systems for CNS Disorders

et al. 2023

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“…Furthermore, EVs can be found in cerebrospinal fluid (CSF) and have been found to cross the BBB, emerging as novel biomarker sources to study neurodegenerative diseases [ 60 , 61 ]. For example, exosomes found in amyloid beta (

) plaques, characteristic of Alzheimer’s disease, have been found to contain specific proteins, suggesting that they could serve as indicators of such [ 49 ].…”

Section: Exosomes As a Subset Of Extracellular Vesicles—their Origin ...mentioning

confidence: 99%

Production and Utility of Extracellular Vesicles with 3D Culture Methods

Ester

Day

2023

Pharmaceutics

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In recent years, extracellular vesicles (EVs) have emerged as promising biomarkers, cell-free therapeutic agents, and drug delivery carriers. Despite their great clinical potential, poor yield and unscalable production of EVs remain significant challenges. When using 3D culture methods, such as scaffolds and bioreactors, large numbers of cells can be expanded and the cell environment can be manipulated to control the cell phenotype. This has been employed to successfully increase the production of EVs as well as to enhance their therapeutic effects. The physiological relevance of 3D cultures, such as spheroids, has also provided a strategy for understanding the role of EVs in the pathogenesis of several diseases and to evaluate their role as tools to deliver drugs. Additionally, 3D culture methods can encapsulate EVs to achieve more sustained therapeutic effects as well as prevent premature clearance of EVs to enable more localised delivery and concentrated exosome dosage. This review highlights the opportunities and drawbacks of different 3D culture methods and their use in EV research.

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“…We demonstrated that exposure to HIV-1 increases EV release from human brain microvascular endothelial cells (HBMEC) and alter their Aβ cargo [ 20 ]. EVs having diverse origin, size, and cargo can be taken up by the target cells via several routes [ 21 ]. Importantly, HBMEC-derived EVs (HBMEC-EVs) carrying Aβ can be transferred to other cells of the neurovascular unit, including neural progenitor cells (NPCs), causing NPC dysfunction and their aberrant neurogenesis [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicle-Serpine-1 Affects Neural Progenitor Cell Mitochondrial Networks and Synaptic Density: Modulation by Amyloid Beta and HIV-1

András¹,

Serrano²,

Djuraskovic³

et al. 2023

Mol Neurobiol

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Brain endothelial extracellular vesicles carrying amyloid beta (EV-Aβ) can be transferred to neural progenitor cells (NPCs) leading to NPC dysfunction. However, the events involved in this EV-mediated Aβ pathology are unclear. EV-proteomics studies identified Serpine-1 (plasminogen activator inhibitor 1, PAI-1) as a major connecting “hub” on several protein–protein interaction maps. Serpine-1 was described as a key player in Aβ pathology and was linked to HIV-1 infection as well. Therefore, the aim of this work was to address the hypothesis that Serpine-1 can be transferred via EVs from brain endothelial cells (HBMEC) to NPCs and contribute to NPC dysfunction. HBMEC concentrated and released Serpine-1 via EVs, the effect that was potentiated by HIV-1 and Aβ. EVs loaded with Serpine-1 were readily taken up by NPCs, and HIV-1 enhanced this event. Interestingly, a highly specific Serpine-1 inhibitor PAI039 increased EV-Aβ transfer to NPCs in the presence of HIV-1. PAI039 also partially blocked mitochondrial network morphology alterations in the recipient NPCs, which developed mainly after HIV + Aβ-EV transfer. PAI039 partly attenuated HIV-EV-mediated decreased synaptic protein levels in NPCs, while increased synaptic protein levels in NPC projections. These findings contribute to a better understanding of the complex mechanisms underlying EV-Serpine-1 related Aβ pathology in the context of HIV infection. They are relevant to HIV-1 associated neurocognitive disorders (HAND) in an effort to elucidate the mechanisms of neuropathology in HIV infection.

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Overcoming Blood-Brain Barrier Resistance: Implications for Extracellular Vesicle-Mediated Drug Brain Delivery

Cited by 8 publications

References 119 publications

Exploring the Potential of Cannabinoid Nanodelivery Systems for CNS Disorders

Exploring the Potential of Cannabinoid Nanodelivery Systems for CNS Disorders

Production and Utility of Extracellular Vesicles with 3D Culture Methods

Extracellular Vesicle-Serpine-1 Affects Neural Progenitor Cell Mitochondrial Networks and Synaptic Density: Modulation by Amyloid Beta and HIV-1

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