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Background: Blood-brain barrier (BBB) is a crucial but dynamic structure that functions as a gatekeeper for the central nervous system (CNS). Managing sufficient substances across the BBB is a major challenge, especially in the development of therapeutics for CNS disorders.
Methods: To achieve an efficient, fast and safe strategy for BBB opening, an acoustofluidic transwell (AFT) was developed for reversible disruption of the BBB. The proposed AFT was consisted of a transwell insert where the BBB model was established, and a surface acoustic wave (SAW) transducer realized using open-source electronics based on printed circuit board techniques.
Results: In the AFT device, the SAW produced acousto-mechanical stimulations to the BBB model resulting in decreased transendothelial electrical resistance in a dose dependent manner, indicating the disruption of the BBB. Moreover, SAW stimulation enhanced transendothelial permeability to sodium fluorescein and FITC-dextran with various molecular weight in the AFT device. Further study indicated BBB opening was mainly attributed to the apparent stretching of intercellular spaces. An in vivo study using a zebrafish model demonstrated SAW exposure promoted penetration of sodium fluorescein to the CNS.
Conclusions: In summary, AFT effectively disrupts the BBB under the SAW stimulation, which is promising as a new drug delivery methodology for neurodegenerative diseases.
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http://dx.doi.org/10.1186/s40824-023-00406-6 | DOI Listing |
Biomed Pharmacother
December 2024
Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States. Electronic address:
The technology of focused ultrasound-mediated disruption of the blood-brain barrier (FUS-BBB opening) has now been used in over 20 Phase 1 clinical trials to validate the safety and feasibility of BBB opening for drug delivery in patients with brain tumors and neurodegenerative diseases. The primary treatment parameters, FUS intensity and microbubble dose, are chosen to balance sufficient BBB disruption to achieve drug delivery against potential acute vessel damage leading to microhemorrhage. However, other safety considerations due to second order effects caused by BBB disruption, such as inflammation and alteration of neurovascular function, are only beginning to be understood.
View Article and Find Full Text PDFEur J Pharmacol
December 2024
Institute of Neurology, General Hospital of Shenyang Military Command, Shenyang, Liaoning 110016, China. Electronic address:
Bioorg Chem
December 2024
Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia.
Red grapes contain resveratrol (Resv), a polyphenol with anti-inflammatory, anti-diabetic, and anticancer properties. In this study, in silico molecular docking was used to assess the binding affinity of Resv to target proteins. Resv was encapsulated in PEGylated liposomes (LNPs) using Phospholipon 90G, cholesterol, and DSPE-mPEG.
View Article and Find Full Text PDFHeliyon
December 2024
Gulbenkian Institute for Molecular Medicine, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, Lisbon, 1649-028, Portugal.
Brain metastases (BM) are frequently found in cancer patients and, though their precise incidence is difficult to estimate, there is evidence for a correlation between BM and specific primary cancers, such as lung, breast, and skin (melanoma). Among all these, breast cancer is the most frequently diagnosed among women and, in this case, BM cause a critical reduction of the overall survival (OS), especially in triple negative breast cancer (TNBC) patients. The main challenge of BM treatment is the impermeable nature of the blood-brain barrier (BBB), which shields the central nervous systems (CNS) from chemotherapeutic drugs.
View Article and Find Full Text PDFFront Cell Neurosci
December 2024
Institute of Pharmaceutical Technology, Goethe University Frankfurt, Frankfurt am Main, Germany.
The pathophysiological role of Aβ oligomers in the onset of Alzheimer's disease (AD) is heavily disputed, pivoting research toward investigating mixed oligomers composed of Aβ and Aβ, which is more abundant but less aggregation-prone. This study investigates Aβ:Aβ oligomers in different ratios, examining their adverse effects on endothelial cells, neurons, astroglia, and microglia, as well as in a human blood-brain barrier (BBB) model. Combining label-free Raman microscopy with complementary imaging techniques and biochemical assays, we show the prominent impact of Aβ on Aβ fibrillation, suggesting an inhibitory effect on aggregation.
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