Evaluation of Drug Blood-Brain-Barrier Permeability Using a Microfluidic Chip

The blood-brain-barrier (BBB) is made up of blood vessels whose permeability enables the passage of some compounds. A predictive model of BBB permeability is important in the early stages of drug development. The predicted BBB permeabilities of drugs have been confirmed using a variety of in vitro m...

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Main Authors: Jung Yoon Yang (Author), Dae-Seop Shin (Author), Moonkyu Jeong (Author), Seong Soon Kim (Author), Ha Neul Jeong (Author), Byung Hoi Lee (Author), Kyu-Seok Hwang (Author), Yuji Son (Author), Hyeon-Cheol Jeong (Author), Chi-Hoon Choi (Author), Kyeong-Ryoon Lee (Author), Myung Ae Bae (Author)
Format: Book
Published: MDPI AG, 2024-04-01T00:00:00Z.
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Summary:The blood-brain-barrier (BBB) is made up of blood vessels whose permeability enables the passage of some compounds. A predictive model of BBB permeability is important in the early stages of drug development. The predicted BBB permeabilities of drugs have been confirmed using a variety of in vitro methods to reduce the quantities of drug candidates needed in preclinical and clinical trials. Most prior studies have relied on animal or cell-culture models, which do not fully recapitulate the human BBB. The development of microfluidic models of human-derived BBB cells could address this issue. We analyzed a model for predicting BBB permeability using the Emulate BBB-on-a-chip machine. Ten compounds were evaluated, and their permeabilities were estimated. Our study demonstrated that the permeability trends of ten compounds in our microfluidic-based system resembled those observed in previous animal and cell-based experiments. Furthermore, we established a general correlation between the partition coefficient (<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mrow><mi>K</mi></mrow><mrow><mi>p</mi></mrow></msub></mrow></semantics></math></inline-formula>) and the apparent permeability (<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mrow><mi>P</mi></mrow><mrow><mi>a</mi><mi>p</mi><mi>p</mi></mrow></msub></mrow></semantics></math></inline-formula>). In conclusion, we introduced a new paradigm for predicting BBB permeability using microfluidic-based systems.
Item Description:10.3390/pharmaceutics16050574
1999-4923