Title:Targeting the Brain: Advances in Drug Delivery
Volume: 13
Issue: 12
Author(s): James P. Blumling III and Gabriel A. Silva
Affiliation:
Keywords:
Blood-brain barrier, brain, central nervous system, drug delivery, liposome, molecular trojan horse, nanoparticle, transcranial, transnasal, transvascular, cell-penetrating peptides (CPPs), molecular trojan horses (MTHs), tandem systems, BBB endothelium
Abstract: The blood-brain barrier (BBB) represents a significant obstacle for drug delivery to the brain. Many therapeutics
with potential for treating neurological conditions prove incompatible with intravenous delivery simply because of
this barrier. Rather than modifying drugs to penetrate the BBB directly, it has proven more efficacious to either physically
bypass the barrier or to use specialized delivery vehicles that circumvent BBB regulatory mechanisms. Controlled-release
intracranial polymer implants and particle injections are the clinical state of the art with regard to localized delivery, although
these approaches can impose significant surgical risks. Focused ultrasound provides a non-invasive alternative that
may prove more desirable for acute treatment of brain tumors and other conditions requiring local tissue necrosis. For targeting
the brain as a whole, cell-penetrating peptides (CPPs) and molecular trojan horses (MTHs) have demonstrated particular
ability as delivery molecules and will likely see increased application. CPPs are not brain specific but offer the potential
for efficient traversal of the BBB, and tandem systems with targeting molecules may produce extremely effective
brain drug delivery tools. Molecular trojan horses utilize receptor-mediated transcytosis to transport cargo and are thus
limited by the quantity of relevant receptors; however, they can be very selective for the BBB endothelium and have
shown promise in gene therapy.
