Crossing the blood-brain barrier with unconventional means

A healthy blood-brain barrier (BBB) is like a sealed window on a blustery day — the inside of the room will stay warm while the freezing air is trapped outside. In the same way a window with leaky insulation will let in cold air and snow, a diseased BBB is more permeable to foreign substances that can worsen neurological conditions.

This permeability can provide an advantage, however, since a diseased BBB can also let in therapeutics. Ava Zoba and Christina Tringides wrote a review on the material considerations for getting these drugs across the BBB.

“The role of the BBB is to create a tight seal that prevents foreign objects from entering the brain through the bloodstream,” said Zoba. “As a result, drugs that are administered systemically through vasculature can have challenges in crossing the BBB; the size of the drug, its charge, and its concentration are all contributing factors.”

Nanoparticles are a promising vehicle due to their size, and they can be “decorated” with drugs that can be carried across the barrier. Nanoparticles can also carry out specific tasks due to their magnetism, porosity, and local heating capabilities.

Carriers like lipid nanoparticles, for example, and liposomes can match the native structure of molecules that are already allowed through the BBB, allowing the carriers to sneak in.

Not only are the materials important, but it is possible to take advantage of the BBB’s natural affinity to be more “open.”

“There are a lot of interesting strategies in trying to temporarily open or permeate the BBB to allow drugs to cross and treat a variety of neurodegenerative diseases, neurological disorders, and cancers,” Zoba said.

Source: “Material considerations for delivering therapeutics across the blood-brain barrier,” by Ava N. Zoba and Christina M. Tringides, APL Materials (2025). The article can be accessed at https://doi.org/10.1063/5.0284305 .