期刊
JOURNAL OF CONTROLLED RELEASE
卷 273, 期 -, 页码 108-130出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2018.01.024
关键词
Blood-brain barrier; In vitro tissue models; Microfluidics; Organ-on-chip; Biomimetic BBB-on-chip; Computational modeling; Nanotechnology; Drug delivery; Drug discovery
资金
- Alberta Prion Research Institute
- Alberta Innovates BioSolutions
- Natural Sciences and Engineering Research of Canada
- Qatar Foundation [NPRP9-144-3-021]
- GCC [GCC-2017-005]
- Qatar University [QUUG-CENG-MIE-15/16-7, QUST-CENG-FALL-15/16-20]
- American University of Beirut
- CNRS grant from National Council for Scientific Research, Lebanon
The blood-brain barrier (BBB) plays a crucial role in maintaining brain homeostasis and transport of drugs to the brain. The conventional animal and Transwell BBB models along with emerging microfluidic-based BBB-on-chip systems have provided fundamental functionalities of the BBB and facilitated the testing of drug delivery to the brain tissue. However, developing biomimetic and predictive BBB models capable of reasonably mimicking essential characteristics of the BBB functions is still a challenge. In addition, detailed analysis of the dynamics of drug delivery to the healthy or diseased brain requires not only biomimetic BBB tissue models but also new systems capable of monitoring the BBB microenvironment and dynamics of barrier function and delivery mechanisms. This review provides a comprehensive overview of recent advances in microengineering of BBB models with different functional complexity and mimicking capability of healthy and diseased states. It also discusses new technologies that can make the next generation of biomimetic human BBBs containing integrated biosensors for real-time monitoring the tissue microenvironment and barrier function and correlating it with the dynamics of drug delivery. Such integrated system addresses important brain drug delivery questions related to the treatment of brain diseases. We further discuss how the combination of in vitro BBB systems, computational models and nanotechnology supports for characterization of the dynamics of drug delivery to the brain.
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