Material considerations for delivering therapeutics across the blood–brain barrier

Therapeutic drug delivery across the blood–brain barrier (BBB) has been a challenging feat for centuries. The intricate nature of the BBB is protected by multiple lines of defense through its neurovascular unit and subsequent junctions that enclose adjacent endothelial cells. Despite the highly selective membrane, many advancements in therapeutic delivery have been made. The utilization of various transport routes both in the paracellular and transcellular spaces has provided progress for incorporating different carrier materials that are used to transport drugs across the BBB. Specific to the transport mechanism used, certain encapsulations, coatings, surfactants, or other targeting molecules can be added to enhance the penetration of the BBB. In a healthy state, the BBB allows native nutrients, amino acids, and ions to enter the brain parenchyma from the bloodstream and restricts toxins, drugs, or non-native molecules from entering the brain. In a diseased state, the integrity, permeability, and function of the BBB are altered, which allows the influx of harmful substances into the brain without regulation. This provides a double-edged sword, as it creates a new avenue for drugs to enter the brain, which can help to cure certain elements of central nervous system diseases while also making the brain more susceptible to other toxins and substances that can exacerbate the diseased state.