Related Experiment Video
Updated: Jun 27, 2026
16:26
Setting-up an In Vitro Model of Rat Blood-brain Barrier (BBB): A Focus on BBB Impermeability and Receptor-mediated Transport
Published on: June 28, 2014
Macromolecular delivery across the blood-brain barrier
1Department of Medical Biophysics, University of Toronto and Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, ON, Canada.
Methods in Molecular Biology (Clifton, N.J.)
|December 17, 2008
Summary
Focused ultrasound and microbubbles enable noninvasive blood-brain barrier disruption for enhanced central nervous system drug delivery. This image-guided method offers a novel approach for treating brain disorders.
Area of Science:
- Neuroscience
- Biomedical Engineering
- Pharmacology
Background:
- The blood-brain barrier (BBB) severely restricts macromolecule delivery into the central nervous system (CNS).
- Effective CNS drug delivery remains a significant challenge in treating neurological diseases.
Purpose of the Study:
- To describe a method for MRI-guided, focused, and noninvasive blood-brain barrier disruption (BBBD).
- To enable enhanced macromolecular drug delivery into the CNS.
Main Methods:
- Utilizing focused ultrasound exposure combined with intravascular injection of pre-formed microbubbles.
- Employing magnetic resonance imaging (MRI) for real-time guidance and monitoring of focal BBBD in animal models.
Main Results:
- Demonstrated successful, localized, and transient disruption of the BBB.
- Established a detailed protocol for MRI-guided focal BBBD in preclinical settings.
Conclusions:
- MRI-guided focused ultrasound and microbubbles provide a safe and effective method for noninvasive BBBD.
- This technique holds promise for a new era of CNS macromolecular drug delivery and brain therapy.
Related Concept Videos
00:49The Blood-brain Barrier
Overview
01:25Physiological Barriers
Physiological barriers are semi-permeable cellular structures restricting drug diffusion into intracellular compartments and tissues. There are six types of physiological barriers: blood endothelial, cell membrane, blood-brain, blood-cerebrospinal fluid (CSF), blood-placenta, and blood-testis barriers.
The blood endothelial barrier is the most porous of these. It allows all small ionized, un-ionized, and lipophilic molecules to pass through the endothelial lining into the interstitial space...
The blood endothelial barrier is the most porous of these. It allows all small ionized, un-ionized, and lipophilic molecules to pass through the endothelial lining into the interstitial space...
01:29Drug Delivery: Parenteral Route
The parenteral route is a critical method of drug administration. It delivers compounds directly into the systemic circulation and bypasses the gastrointestinal tract. This approach is particularly advantageous for drugs that exhibit poor absorption or instability when administered orally.
There are three primary parenteral routes: intravenous (IV), intramuscular (IM), and subcutaneous (SC). The IV route introduces the drug directly into the bloodstream, ensuring immediate action. The IM route...
There are three primary parenteral routes: intravenous (IV), intramuscular (IM), and subcutaneous (SC). The IV route introduces the drug directly into the bloodstream, ensuring immediate action. The IM route...
01:23Factors Affecting Drug Distribution: Physiological Barriers
Drug distribution in the body is intricately regulated by various physiological barriers that control the passage of substances. These include the capillary endothelial barrier, the blood-brain, blood-cerebrospinal fluid, blood-placental, and blood-testis barriers.
The capillary endothelial barrier allows only smaller molecules below 600 Da (Daltons) to pass through. It also restricts drugs like heparin that are bound to blood components, limiting their movement within the bloodstream.
The...
The capillary endothelial barrier allows only smaller molecules below 600 Da (Daltons) to pass through. It also restricts drugs like heparin that are bound to blood components, limiting their movement within the bloodstream.
The...
01:23Mechanisms of Drug Absorption: Paracellular, Transcellular, and Vesicular Transport
Drugs need to permeate cell membranes to reach their target sites after administration. Orally administered drugs must transcend intestinal epithelial membrane barriers to infiltrate the systemic circulation. Drugs with a molecular weight of less than 500 Daltons diffuse through gaps between neighboring cells, called paracellular pathways.
However, most drugs use the transcellular route, traversing directly through the cell membranes via two mechanisms: passive and active transport. Passive...
However, most drugs use the transcellular route, traversing directly through the cell membranes via two mechanisms: passive and active transport. Passive...
01:24Cellular Membranes and Drug Transport
Drugs must traverse multiple biological barriers, such as multi-layered skin, single-layered intestinal epithelium, and the plasma membrane, to reach their target sites within the body. The plasma membrane, a highly structured composite of phospholipids, carbohydrates, and proteins, is the cell's protective boundary, facilitating selective substance exchange.
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.