Revisiting intra-arterial drug delivery for treating brain diseases or is it "déjà-vu, all over again"?
Revisiting intra-arterial drug delivery for treating brain diseases or is it "déjà-vu, all over again"?
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DOI：
10.4103/2348-0548.130386
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发表时间：
2014-05
影响因子：
--
通讯作者：
Emala CW
中科院分区：
文献类型：
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作者：
Joshi S;Ellis JA;Emala CW
六十多年来，动脉内（IA）药物已零星用于治疗致命性脑部疾病。近年来，在视网膜母细胞瘤、肝癌和局部浸润性乳腺癌的IA治疗中取得了相当大的进展，但在脑癌的治疗中取得的进展相对较小。与其他器官相比，高静息血流量和血脑屏障（BBB）的存在使得IA递送至脑组织更具挑战性。该领域缺乏进展的部分原因还在于无法理解IA药物的复杂药代动力学，因为难以通过常规化学方法在亚秒时间范围内跟踪药物浓度。光学成像的进步现在为IA药物和光学示踪剂递送的药代动力学提供了前所未有的见解。新的递送方法，改进的IA药物制剂和光学药代动力学，为我们提供了未经测试的药理学范例，可能导致脑癌和中风的新治疗干预。本次审查的目的是把重点放在目前的做法，问题，和潜在的IA药物输送治疗脑部疾病。介入神经放射学界需要在基础科学（药理学和药物成像）和转化（药物输送技术和方案开发）水平上共同努力，以推动该领域的发展。
For over six decades intra-arterial (IA) drugs have been sporadically used for the treatment of lethal brain diseases. In recent years considerable advance has been made in the IA treatment of retinoblastomas, liver and locally invasive breast cancers, but relatively little progress has been made in the treatment of brain cancers. High resting blood flow and the presence of the blood-brain barrier (BBB), makes IA delivery to the brain tissue far more challenging, compared to other organs. The lack of advance in the field is also partly due to the inability to understand the complex pharmacokinetics of IA drugs as it is difficult to track drug concentrations in sub-second time frame by conventional chemical methods. The advances in optical imaging now provide unprecedented insights into the pharmacokinetics of IA drug and optical tracer delivery. Novel delivery methods, improved IA drug formulations, and optical pharmacokinetics, present us with untested paradigms in pharmacology that could lead to new therapeutic interventions for brain cancers and stroke. The object of this review is to bring into focus the current practice, problems, and the potential of IA drug delivery for treating brain diseases. A concerted effort is needed at basic sciences (pharmacology and drug imaging), and translational (drug delivery techniques and protocol development) levels by the interventional neuroradiology community to advance the field.