In vitro models and systems for evaluating the dynamics of drug delivery to the healthy and diseased brain

Hassan Pezeshgi Modarres; Mohsen Janmaleki; Mana Novin; John Saliba; Fatima El-Hajj; Mahdi RezayatiCharan; Amir Seyfoori; Hamid Sadabadi; Milène Vandal; Minh Dang Nguyen; Anwarul Hasan; Amir Sanati-Nezhad

doi:10.1016/j.jconrel.2018.01.024

In vitro models and systems for evaluating the dynamics of drug delivery to the healthy and diseased brain

J Control Release. 2018 Mar 10:273:108-130. doi: 10.1016/j.jconrel.2018.01.024. Epub 2018 Feb 6.

Affiliations

¹ BioMEMS and Bioinspired Microfluidic Laboratory, Department of Mechanical and Manufacturing Engineering, University of Calgary, Calgary, Canada; Center for BioEngineering Research and Education, University of Calgary, Calgary, Canada.
² Biomedical Engineering, Department of Mechanical Engineering, Faculty of Engineering and Architecture, American University of Beirut, Beirut 1107 2020, Lebanon.
³ Breast Cancer Research Center (BCRC), ACECR, Tehran, Iran; School of Mechanical Engineering, College of Engineering, University of Tehran, Tehran, Iran.
⁴ Breast Cancer Research Center (BCRC), ACECR, Tehran, Iran; School of Metallurgy and Materials Engineering, College of Engineering, University of Tehran, Tehran, Iran.
⁵ Departments of Clinical Neurosciences, Cell Biology and Anatomy, Biochemistry and Molecular Biology, University of Calgary, Calgary, Canada.
⁶ Biomedical Engineering, Department of Mechanical Engineering, Faculty of Engineering and Architecture, American University of Beirut, Beirut 1107 2020, Lebanon; Department of Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha, 2713, Qatar.
⁷ BioMEMS and Bioinspired Microfluidic Laboratory, Department of Mechanical and Manufacturing Engineering, University of Calgary, Calgary, Canada; Center for BioEngineering Research and Education, University of Calgary, Calgary, Canada. Electronic address: amir.sanatinezhad@ucalgary.ca.

PMID: 29378233
DOI: 10.1016/j.jconrel.2018.01.024

Abstract

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.

Keywords: Biomimetic BBB-on-chip; Blood-brain barrier; Computational modeling; Drug delivery; Drug discovery; In vitro tissue models; Microfluidics; Nanotechnology; Organ-on-chip.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Biomimetics
Brain / metabolism*
Brain Diseases / drug therapy
Drug Delivery Systems*
Humans