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Development of a local drug transport mechanism through the blood brain barrier via magnetic nanoparticles induced hypothermia

通过磁性纳米颗粒诱导低温，开发通过血脑屏障的局部药物转运机制

基本信息

批准号：
250944-2012
负责人：
Martel, Sylvain
金额：
$ 6.32万
依托单位：
École Polytechnique de Montréal
依托单位国家：
加拿大
项目类别：
Discovery Grants Program - Individual
财政年份：
2015
资助国家：
加拿大
起止时间：
2015-01-01 至 2016-12-31
项目状态：
已结题

来源：
https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=570934
关键词：
Development local drug transport mechanism

项目摘要

Drug delivery to the brain remains a challenge mainly because of impermeable barrier that exists between the blood and the brain tissue. In fact, nearly 98% of drugs used in the Central Nervous System (CNS) to combat brain disorders cannot enter the brain following direct intravenous injection. Also, while drugs influence the unhealthy tissue, they may as well promote side effects in the healthy tissue. The extremely selective permeability of the mentioned barrier and high side effects of certain drugs reinforce the importance of localized drug delivery to the brain. Previously, our team has shown successful local delivery and tracking of therapeutic agents by means of miniaturized drug carriers inside the liver vasculature of a living animal using a modified Magnetic Resonance (MR) scanner. These carriers consist of drug molecules and aggregates of extremely small particles. Here, the same particles are synthesized to offer heat to their surroundings once placed inside an alternating magnetic field. This heat leads to disruption of the barrier and increases its permeability towards drug molecules. Therefore, by positioning the miniaturized drug carriers near the barrier and application of heat, one can create an opening for drug molecules to enter the brain tissue.

药物输送到大脑仍然是一个挑战，主要是因为血液和脑组织之间存在不可渗透的屏障。事实上，近98%用于中枢神经系统（CNS）治疗脑部疾病的药物在直接静脉注射后无法进入大脑。此外，虽然药物会影响不健康的组织，但它们也可能会促进健康组织的副作用。上述屏障的极选择性渗透性和某些药物的高副作用强化了局部药物递送至大脑的重要性。此前，我们的团队已经使用改良的磁共振（MR）扫描仪，通过活体动物肝脏血管内的微型药物载体成功地进行了治疗药物的局部递送和追踪。这些载体由药物分子和极小颗粒的聚集体组成。在这里，相同的粒子被合成，一旦放置在交变磁场中，就会向周围环境提供热量。这种热量会破坏屏障并增加其对药物分子的渗透性。因此，通过将微型药物载体放置在屏障附近并施加热量，可以为药物分子进入脑组织创造一个开口。