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Current Pharmaceutical Biotechnology


ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Targeting the Brain: Advances in Drug Delivery

Author(s): James P. Blumling III and Gabriel A. Silva

Volume 13, Issue 12, 2012

Page: [2417 - 2426] Pages: 10

DOI: 10.2174/138920112803341833

Price: $65


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.

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

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