The blood-brain barrier (BBB)… excludes from the brain ~100% of large-molecule neurotherapeutics and more than 98% of all small-molecule drugs.
[T]he minimal BBB transport of the majority of all potential CNS [central nervous system] drugs, leads predictably to the present situation in neurotherapeutics, which is that there are few effective treatments for the majority of CNS disorders.
[For example,] histamine readily crosses the porous capillaries perfusing all peripheral tissues but is excluded from entry into the brain or spinal cord by the BBB.
[M]ost drugs do not cross the BBB.
BBB is solubilized with high dose ethanol, DMSO, SDS, Tween 80 (polysorbate-80).
Freunds adjuvant opens BBB to IgG for weeks; enable IgG uptake into brain in rodent vaccine models…
In parallel with trans-cranial brain drug delivery strategies, there has been a significant effort in delivering drugs to the brain with BBB disruption…
The BBB, like cell membranes in general, is subject to solvent-mediated disruption with chemicals such as… Tween 80 also known as polysorbate-80.
There are numerous examples in the literature where the peripheral administration of a drug, which normally should not cross the BBB, is followed by pharmacological activity in the brain.
[An] explanation is that the drug is injected in a diluent that is membrane destabilizing, and causes BBB disruption. Often the drug is solubilized in solvents such as… a Tween detergent…
Tween 80, also known as polysorbate-80, is frequently administered in CNS drug formulations.
Analgesia with kyotorphin, a oligopeptide that normally does not cross the BBB, is possible following the peripheral administration of the peptide, providing Tween 80 is coadministered.
If a CNS drug is formulated in a vehicle other than a physiological buffer, then the amounts of any solvent, surfactant, or adjuvant, that are included in the formulation should be evaluated critically as to whether drug treatment is associated with solvent-mediated BBB disruption. In this setting, there is a high likelihood that chronic drug administration will have toxic side effects.