Safety and efficacy of an anti-claudin-5 monoclonal antibody to increase blood–brain barrier permeability for drug delivery to the brain in a non-human primate

2021 ◽  
Author(s):  
Keisuke Tachibana ◽  
Yosuke Hashimoto ◽  
Keisuke Shirakura ◽  
Yoshiaki Okada ◽  
Ryuichi Hirayama ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Monoclonal Antibody ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Safety And Efficacy ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Brain Barrier Permeability ◽  
The Brain ◽  
Human Primate

Ligand and Structure-based Modeling of Passive Diffusion through the Blood-Brain Barrier

2018 ◽  
Vol 25 (9) ◽  
pp. 1073-1089 ◽  
Author(s):  
Santiago Vilar ◽  
Eduardo Sobarzo-Sanchez ◽  
Lourdes Santana ◽  
Eugenio Uriarte
Keyword(s):  
Blood Brain Barrier ◽  
In Silico ◽  
Passive Diffusion ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
Different Types ◽  
The Brain

Background: Blood-brain barrier transport is an important process to be considered in drug candidates. The blood-brain barrier protects the brain from toxicological agents and, therefore, also establishes a restrictive mechanism for the delivery of drugs into the brain. Although there are different and complex mechanisms implicated in drug transport, in this review we focused on the prediction of passive diffusion through the blood-brain barrier. Methods: We elaborated on ligand-based and structure-based models that have been described to predict the blood-brain barrier permeability. Results: Multiple 2D and 3D QSPR/QSAR models and integrative approaches have been published to establish quantitative and qualitative relationships with the blood-brain barrier permeability. We explained different types of descriptors that correlate with passive diffusion along with data analysis methods. Moreover, we discussed the applicability of other types of molecular structure-based simulations, such as molecular dynamics, and their implications in the prediction of passive diffusion. Challenges and limitations of experimental measurements of permeability and in silico predictive methods were also described. Conclusion: Improvements in the prediction of blood-brain barrier permeability from different types of in silico models are crucial to optimize the process of Central Nervous System drug discovery and development.

scholarly journals Penetration of the blood-brain barrier: enhancement of drug delivery and imaging by bacterial glycopeptides.

1995 ◽  
Vol 182 (4) ◽  
pp. 1037-1043 ◽  
Author(s):  
B Spellerberg ◽  
S Prasad ◽  
C Cabellos ◽  
M Burroughs ◽  
P Cahill ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Parenchyma ◽  
Brain Barrier ◽  
Dependent Manner ◽  
Pharmacological Agents ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
The Brain

The blood-brain barrier restricts the passage of many pharmacological agents into the brain parenchyma. Bacterial glycopeptides induce enhanced blood-brain barrier permeability when they are present in the subarachnoid space during meningitis. By presenting such glycopeptides intravenously, blood-brain barrier permeability in rabbits was enhanced in a reversible time- and dose-dependent manner to agents < or = 20 kD in size. Therapeutic application of this bioactivity was evident as enhanced penetration of the antibiotic penicillin and the magnetic resonance imaging contrast agent gadolinium-diethylene-triamine-pentaacetic acid into the brain parenchyma.

scholarly journals Evaluating blood-brain barrier permeability in a rat model of type 2 diabetes

2020 ◽  
Author(s):  
Craig Ferris ◽  
Ju Qiao ◽  
Christopher M Lawson ◽  
Kilian FG Rentrup ◽  
Praveen Kulkarni
Keyword(s):  
Type 2 Diabetes ◽  
Blood Brain Barrier ◽  
Small Vessel Disease ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
The Brain

Abstract Background This is an exploratory study using a novel imaging modality, quantitative ultrashort time-to-echo, contrast enhanced (QUTE-CE) magnetic resonance imaging to evaluate the permeability of the blood brain barrier in a rat model of type 2 diabetes with the presumption that small vessel disease is a contributing factor to neuropathology in diabetes. Methods The BBZDR/Wor rat, a model of type 2 diabetes, and age-matched controls were studied for changes in blood brain barrier permeability. QUTE-CE, a quantitative vascular biomarker, generated angiographic images with over 500,000 voxels that were registered to a 3D MRI rat brain atlas providing site-specific information on blood-brain barrier permeability in 173 different brain areas. Results In this model of diabetes, without the support of insulin treatment, there was global capillary pathology with over 84% of the brain showing a significant increase in blood brain barrier permeability over wild-type controls. Areas of the cerebellum and midbrain dopaminergic system were not significantly affected.Conclusion Small vessel disease as assessed by permeability in the blood brain barrier in type 2 diabetes is pervasive and includes much of the brain. The increase in blood-brain barrier permeability is a likely contributing factor to diabetic encephalopathy and dementia.

scholarly journals Stereotactic modulation of blood-brain barrier permeability to enhance drug delivery

2016 ◽  
Vol 18 (12) ◽  
pp. 1601-1609 ◽  
Author(s):  
Geoff Appelboom ◽  
Alexandre Detappe ◽  
Melissa LoPresti ◽  
Sijumon Kunjachan ◽  
Stefan Mitrasinovic ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability
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