Therapeutic strategies to improve drug delivery across the blood-brain barrier.
Therapeutic strategies to improve drug delivery across the blood-brain barrier.
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DOI：
10.3171/2014.12.focus14758
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发表时间：
2015-03
影响因子：
4.1
通讯作者：
Grant GA
中科院分区：
文献类型：
--
作者：
Azad TD;Pan J;Connolly ID;Remington A;Wilson CM;Grant GA
切除脑肿瘤后进行化疗和放疗，以消除剩余的恶性细胞群。针对这些人群可以减少肿瘤复发，并提供更完整的治疗方法。因此，改善肿瘤的可及性，同时使正常脑组织不受损害，是一个关键的追求。这一奋进的核心挑战在于将治疗剂有限地递送到肿瘤本身。血脑屏障（BBB）是造成这种困难的主要原因，但也提供了与体循环的必要隔离。由于血脑屏障的物理和化学限制，目前的许多疗法，从细胞毒性药物到基于抗体的蛋白质，都无法进入肿瘤。本文综述了血脑屏障的特点和相关的变化所造成的肿瘤的存在。目前的战略，以提高整个血脑屏障的治疗肿瘤的交付将进行讨论，与寻求破坏血脑屏障和那些旨在规避它的战略之间的区别。
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.