Transcellular Model for Neutral and Charged Nanoparticles Across an In Vitro Blood–Brain Barrier

Autor: Guanglei Li, Jie Fan, Lin Zhang, Zhaokai Yin, Bingmei M. Fu
Rok vydání: 2020
Předmět:
Surface Properties
Transcellular model
0206 medical engineering
Biomedical Engineering
Nanoparticle
02 engineering and technology
030204 cardiovascular system & hematology
Blood–brain barrier
Models
Biological
Charge
Permeability
Cell Line
Capillary Permeability
Glycocalyx
Cell membrane
Mice
03 medical and health sciences
0302 clinical medicine
Electricity
bEnd3 (mouse brain microvascular endothelial cells)
mental disorders
medicine
Animals
Particle Size
Transcellular
Drug Carriers
Chemistry
technology
industry
and agriculture
020601 biomedical engineering
In vitro
Kinetics
medicine.anatomical_structure
Blood-Brain Barrier
Permeability (electromagnetism)
Drug delivery
cardiovascular system
Biophysics
Nanoparticles
Polystyrenes
Original Article
Transcytosis
Cardiology and Cardiovascular Medicine
Zdroj: Cardiovascular Engineering and Technology
ISSN: 1869-4098
1869-408X
DOI: 10.1007/s13239-020-00496-6
Popis: Purpose The therapeutic drug-loaded nanoparticles (NPs, 20–100 nm) have been widely used to treat brain disorders. To improve systemic brain delivery efficacy of these NPs, it is necessary to quantify their transport parameters across the blood–brain barrier (BBB) and understand the underlying transport mechanism. Methods Permeability of an in vitro BBB, bEnd3 (mouse brain microvascular endothelial cells) monolayer, to three neutral NPs with the representative diameters was measured using an automated fluorometer system. To elucidate the transport mechanism of the neutral NPs across the in vitro BBB, and that of positively charged NPs whose BBB permeability was measured in a previous study, we developed a novel transcellular model, which incorporates the charge of the in vitro BBB, the mechanical property of the cell membrane, the ion concentrations of the surrounding salt solution and the size and charge of the NPs. Results Our model indicates that the negative charge of the surface glycocalyx and basement membrane of the BBB plays a pivotal role in the transcelluar transport of NPs with diameter 20-100 nm across the BBB. The electrostatic force between the negative charge at the in vitro BBB and the positive charge at NPs greatly enhances NP permeability. The predictions from our transcellular model fit very well with the measured BBB permeability for both neutral and charged NPs. Conclusion Our model can be used to predict the optimal size and charge of the NPs and the optimal charge of the BBB for an optimal systemic drug delivery strategy to the brain.
Databáze: OpenAIRE
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