Therapeutic strategies to improve drug delivery across the blood-brain barrier.
Resection of brain tumors is followed by chemotherapy and radiation to ablate remaining malignant cell populations. Targeting these populations stands to reduce tumor recurrence and offer the promise of more complete therapy. Thus, improving access to the tumor, while leaving normal brain tissue unscathed, is a critical pursuit. A central challenge in this endeavor lies in the limited delivery of therapeutics to the tumor itself. The blood-brain barrier (BBB) is responsible for much of this difficulty but also provides an essential separation from systemic circulation. Due to the BBB's physical and chemical constraints, many current therapies, from cytotoxic drugs to antibody-based proteins, cannot gain access to the tumor. This review describes the characteristics of the BBB and associated changes wrought by the presence of a tumor. Current strategies for enhancing the delivery of therapies across the BBB to the tumor will be discussed, with a distinction made between strategies that seek to disrupt the BBB and those that aim to circumvent it.
Department of Neurosurgery, Stanford University School of Medicine, Stanford, California.
Tej D
TD
Azad
James
J
Pan
Ian D
ID
Connolly
Austin
A
Remington
Christy M
CM
Wilson
Gerald A
GA
Grant
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy; D016503:Drug Delivery Systems; D006801:Humans
D000970:Antineoplastic Agents
ABC = ATP-binding cassette; AQP4 = aquaporin-4; BBB = blood-brain barrier; CED = convection-enhanced delivery; ECM = extracellular matrix; FUS = focused ultrasound; P-glycoprotein; P-gp = P-glycoprotein; WGA = wheat germ agglutinin; ZO = zona occludens; blood-brain barrier; convection-enhanced delivery; focused ultrasound