The blood-brain barrier (BBB) is a highly selective and tightly regulated barrier that separates the circulating blood from the brain tissue. It is composed of specialized endothelial cells that line the blood vessels in the brain, as well as other supporting cells. The main function of the BBB is to protect the brain from potentially harmful substances while allowing essential nutrients and molecules to enter.

Penetrating the blood-brain barrier can be a challenge for many drugs because of its selective permeability. However, there are several mechanisms by which drugs can cross the BBB:

1. Passive Diffusion: Some small lipophilic (fat-soluble) molecules can passively diffuse across the BBB. Lipophilic drugs can dissolve in the lipid membranes of the endothelial cells and enter the brain. However, this method is limited to drugs with specific physicochemical properties.

2. Transporters: The BBB has various transporters that actively transport specific molecules into or out of the brain. These transporters can facilitate the entry of certain drugs into the brain. For example, carrier-mediated transporters can transport essential nutrients like glucose and amino acids across the BBB, and drug molecules that resemble these nutrients can exploit these transporters for brain entry.

3. Receptor-Mediated Transcytosis: Some large molecules, such as peptides or antibodies, can cross the BBB through receptor-mediated transcytosis. This process involves the binding of the drug to specific receptors on the endothelial cells, followed by internalization and transport across the cell to the other side of the barrier.

4. Disruption of the BBB: In certain situations, such as during inflammation or brain injury, the BBB can become temporarily disrupted, allowing greater permeability to various substances, including drugs. However, this method is not ideal for routine drug delivery due to potential risks and lack of selectivity.

5. Nanoparticles and Drug Delivery Systems: Nanoparticles and other drug delivery systems can be designed to encapsulate drugs and enhance their transport across the BBB. These systems can exploit various mechanisms, such as receptor-mediated targeting or bypassing efflux pumps, to increase drug penetration into the brain.

It's important to note that not all drugs can easily cross the blood-brain barrier, and their ability to do so depends on factors such as their molecular size, charge, lipophilicity, and the presence of specific transporters or receptors. Researchers continue to explore and develop innovative strategies to improve drug delivery to the brain and enhance therapeutic outcomes for neurological disorders.

Hi Fani Nur Maftukhah

Here are some good references you can go through.

1. https://bmcneurol.biomedcentral.com/articles/10.1186/1471-2377-9-S1-S3#:~:text=Most%20drugs%20cross%20the%20BBB,favor%20crossing%20by%20this%20mechanism.

2. Article Pardridge, WM. Drug transport across the blood-brain barrier...

3. Article Possible strategies to cross the blood–brain barrier

4. Article Drug Delivery across the Blood-Brain Barrier

Thanks

In dogs with the MDR1 gene fault, P-glycoprotein control varies meaning that there is a genetic component to some drugs being able to cross the blood-brain barrier.

Please go through the below mentioned research

https://pubs.rsc.org/en/content/articlelanding/2023/nr/d2nr07163k