Therapeutic strategies to improve drug delivery across the blood-brain barrier

Mar 3, 2015Neurosurgical focus

Ways to improve medicine delivery through the blood-brain barrier

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Abstract

Limited delivery of therapeutics to brain tumors is primarily due to the blood-brain barrier (BBB).

The BBB provides a crucial separation from systemic circulation but hinders therapeutic access to tumors.
Many existing therapies, including cytotoxic drugs and antibody-based proteins, struggle to penetrate the BBB.
The presence of a tumor can induce changes in the BBB that may affect drug delivery.
Strategies to enhance therapeutic delivery include both disrupting the BBB and circumventing it.

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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.

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Therapeutic strategies to improve drug delivery across the blood-brain barrier

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