The blood–brain barrier: Structure, regulation and drug delivery

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 25, 2023

Abstract Blood–brain barrier (BBB) is a natural protective membrane that prevents central nervous system (CNS) from toxins and pathogens in blood. However, the presence of BBB complicates pharmacotherapy for CNS disorders as most chemical drugs biopharmaceuticals have been impeded to enter brain. Insufficient drug delivery into brain leads low therapeutic efficacy well aggravated side effects due accumulation other organs tissues. Recent breakthrough materials science nanotechnology provides library advanced with customized structure property serving powerful toolkit targeted delivery. In-depth research field anatomical pathological study on further facilitates development brain-targeted strategies enhanced crossing. In this review, physiological different cells contributing are summarized. Various emerging permeability regulation crossing including passive transcytosis, intranasal administration, ligands conjugation, coating, stimuli-triggered disruption, overcome obstacle highlighted. Versatile systems ranging organic, inorganic, biologics-derived their synthesis procedures unique physio-chemical properties summarized analyzed. This review aims provide an up-to-date comprehensive guideline researchers diverse fields, offering perspectives system.

Language: Английский

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Pathophysiology of Blood–Brain Barrier Permeability Throughout the Different Stages of Ischemic Stroke and Its Implication on Hemorrhagic Transformation and Recovery

Frontiers in Neurology, Journal Year: 2020, Volume and Issue: 11

Published: Dec. 9, 2020

The blood-brain barrier (BBB) is a dynamic interface responsible for maintaining the central nervous system homeostasis. Its unique characteristics allow protecting brain from unwanted compounds, but its impairment involved in vast number of pathological conditions. Disruption BBB and increase permeability are key development several neurological diseases have been extensively studied stroke. Ischemic stroke most prevalent type characterized by myriad events triggered an arterial occlusion that can eventually lead to fatal outcomes such as hemorrhagic transformation (HT). seems follow multiphasic pattern throughout different stages associated with distinct biological substrates. In hyperacute stage, sudden hypoxia damages BBB, leading cytotoxic edema increased permeability; acute neuroinflammatory response aggravates injury, higher consequent risk HT be motivated reperfusion therapy; subacute stage (1-3 weeks), repair mechanisms take place, especially neoangiogenesis. Immature vessels show leaky this has improved clinical recovery. chronic (>6 restoration factors leads start decreasing permeability. Nonetheless, will persist some degree weeks after injury. Understanding behind dysregulation pathophysiology could potentially help guide care decisions new therapeutic targets; however, effective translation into practice still lacking. review, we address physiological through ischemic their role

Language: Английский

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Evolution of blood–brain barrier in brain diseases and related systemic nanoscale brain-targeting drug delivery strategies

Acta Pharmaceutica Sinica B, Journal Year: 2020, Volume and Issue: 11(8), P. 2306 - 2325

Published: Dec. 31, 2020

Blood-brain barrier (BBB) strictly controls matter exchange between blood and brain, severely limits brain penetration of systemically administered drugs, resulting in ineffective drug therapy diseases. However, during the onset progression diseases, BBB alterations evolve inevitably. In this review, we focus on nanoscale brain-targeting delivery strategies designed based evolutions related applications various diseases including Alzheimer's disease, Parkinson's epilepsy, stroke, traumatic injury tumor. The advances optimization small molecules for crossing non-systemic administration routes (e.g., intranasal treatment) bypassing are not included review.

Language: Английский

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In vitro Models of Neurodegenerative Diseases

Frontiers in Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 8

Published: May 13, 2020

Neurodegenerative diseases are progressive degenerative conditions characterized by the functional deterioration and ultimate loss of neurons. These incurable debilitating affect millions people worldwide, therefore represent a major global health challenge with severe implications for individuals society. Recently, several neuroprotective drugs have failed in human clinical trials despite promising pre-clinical data, suggesting that conventional cell cultures animal models cannot precisely replicate pathophysiology. To bridge gap between studies, three-dimensional culture been developed from or cells, allowing effects new therapies to be predicted more accurately closely replicating some aspects brain environment, mimicking neuronal glial interactions, incorporating blood flow. In this review, we discuss relative merits different cerebral models, traditional latest high-throughput systems. We their advantages disadvantages as well potential investigate complex mechanisms neurodegenerative diseases. focus on vitro most frequent age-related disorders, such Parkinson's disease, Alzheimer's disease prion multiple sclerosis, chronic inflammatory affecting young adults.

Language: Английский

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Structural, Molecular, and Functional Alterations of the Blood-Brain Barrier during Epileptogenesis and Epilepsy: A Cause, Consequence, or Both?

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(2), P. 591 - 591

Published: Jan. 16, 2020

The blood-brain barrier (BBB) is a dynamic, highly selective primarily formed by endothelial cells connected tight junctions that separate the circulating blood from brain extracellular fluid. lining microvessels are under inductive influence of neighboring cell types, including astrocytes and pericytes. In addition to anatomical characteristics BBB, various specific transport systems, enzymes receptors regulate molecular cellular traffic across BBB. While intact BBB prevents many macromolecules immune entering brain, following epileptogenic insults changes its properties. Among alterations, albumin extravasation diapedesis leucocytes into parenchyma occur, inducing or contributing epileptogenesis. Furthermore, seizures themselves may modulate functions, permitting extravasation, leading activation innate system, eventually modifications neuronal networks. alterations not necessarily associated with enhanced drug penetration brain. Increased expression multidrug efflux transporters such as P-glycoprotein likely act 'second line defense' mechanism protect toxins. A better understanding complex in structure function epilepsy lead novel therapeutic interventions allowing prevention treatment well other detrimental neuro-psychiatric sequelae injury.

Language: Английский

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Blood–Spinal Cord Barrier in Spinal Cord Injury: A Review

Journal of Neurotrauma, Journal Year: 2020, Volume and Issue: 38(9), P. 1203 - 1224

Published: Dec. 9, 2020

The blood-spinal cord barrier (BSCB), a physical between the blood and spinal parenchyma, prevents toxins, cells, pathogens from entering maintains tightly controlled chemical balance in environment, which is necessary for proper neural function. A BSCB disruption, however, plays an important role primary secondary injury processes related to (SCI). After SCI, structure of broken down, leads directly leakage components. At same time, permeability also increased. Repairing disruption could alleviate SCI pathology. We review morphology pathology progression therapeutic methods targeting SCI.

Language: Английский

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Neurodegenerative diseases and effective drug delivery: A review of challenges and novel therapeutics

Journal of Controlled Release, Journal Year: 2020, Volume and Issue: 330, P. 1152 - 1167

Published: Nov. 13, 2020

Language: Английский

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High-Throughput Screening Platforms in the Discovery of Novel Drugs for Neurodegenerative Diseases

Bioengineering, Journal Year: 2021, Volume and Issue: 8(2), P. 30 - 30

Published: Feb. 23, 2021

Neurodegenerative diseases (NDDs) are incurable and debilitating conditions that result in progressive degeneration and/or death of nerve cells the central nervous system (CNS). Identification viable therapeutic targets new treatments for CNS disorders particular, NDDs is a major challenge field drug discovery. These difficulties can be attributed to diversity involved, extreme complexity neural circuits, limited capacity tissue regeneration, our incomplete understanding underlying pathological processes. Drug discovery complex multidisciplinary process. The screening attrition rate current protocols mean only one may arise from millions screened compounds resulting need improve technologies address multiple causes attrition. This has identified screen larger libraries where use efficient high-throughput (HTS) becomes key HTS investigate hundreds thousands per day. However, if fewer could without compromising probability success, cost time would largely reduced. To end, recent advances computer-aided design, silico libraries, molecular docking software combined with upscaling cell-based platforms have evolved efficiency higher predictability clinical applicability. We review, here, increasing role contemporary processes, particular NDDs, evaluate criteria its successful application. also discuss requirement novel NDD therapies examine challenges validating developing NDDs.

Language: Английский

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Blood–Brain Barrier in Brain Tumors: Biology and Clinical Relevance

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(23), P. 12654 - 12654

Published: Nov. 23, 2021

The presence of barriers, such as the blood–brain barrier (BBB) and brain–tumor (BTB), limits penetration antineoplastic drugs into brain, resulting in poor response to treatments. Many techniques have been developed overcome these including direct injections substances by intranasal or intrathecal routes, chemical modification constituents BBB, inhibition efflux pumps, physical disruption BBB radiofrequency electromagnetic radiation (EMP), laser-induced thermal therapy (LITT), focused ultrasounds (FUS) combined with microbubbles convection enhanced delivery (CED). However, most strategies tested only preclinical models phase 1–2 trials, none them approved for treatment brain tumors yet. Concerning metastases, many molecules last years a better across (new generation tyrosine kinase inhibitors like osimertinib non-small-cell lung carcinoma neratinib/tucatinib breast cancer), progression-free survival overall compared older molecules. Promising studies concerning neural stem cells, CAR-T (chimeric antigen receptors) immunotherapy checkpoint are ongoing.

Language: Английский

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Current Strategies for Exosome Cargo Loading and Targeting Delivery

Cells, Journal Year: 2023, Volume and Issue: 12(10), P. 1416 - 1416

Published: May 17, 2023

Extracellular vesicles (EVs) such as ectosomes and exosomes have gained attention promising natural carriers for drug delivery. Exosomes, which range from 30 to 100 nm in diameter, possess a lipid bilayer are secreted by various cells. Due their high biocompatibility, stability, low immunogenicity, favored cargo carriers. The membrane of also offers protection against degradation, making them desirable candidate However, loading into remains be challenge. Despite strategies incubation, electroporation, sonication, extrusion, freeze–thaw cycling, transfection that been developed facilitate loading, inadequate efficiency still persists. This review an overview current delivery using summarizes recent approaches small-molecule, nucleic acid, protein drugs exosomes. With insights these studies, we provide ideas more efficient effective molecules

Language: Английский

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