Cerebrovascular Research Laboratory, Department of Surgical Sciences, Anesthesiology & Intensive Care Medicine, University Hospital, Uppsala University, Uppsala, Sweden.
Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2012 Mar-Apr;4(2):184-203. doi: 10.1002/wnan.172. Epub 2011 Dec 8.
Recent developments in nanomedicine resulted in targeted drug delivery of active compounds into the central nervous system (CNS) either through encapsulated material or attached to nanowires. Nanodrug delivery by any means is supposed to enhance neuroprotection due to rapid accumulation of drugs within the target area and a slow metabolism of the compound. These two factors enhance neuroprotection than the conventions drug delivery. However, this is still uncertain whether nanodrug delivery could alter the pharmacokinetics of compounds making it more effective or just longer exposure of the compound for extended period of time is primarily responsible for enhanced effects of the drugs. Our laboratory is engaged in understanding of the nanodrug delivery using TiO(2) nanowires in CNS injuries models, for example, spinal cord injury (SCI), hyperthermia and/or intoxication of nanoparticles with or without other comorbidity factors, that is, diabetes or hypertension in rat models. Our observations suggest that nanowired drug delivery is effective under normal situation of SCI and hyperthermia as evidenced by significant reduction in the blood-brain barrier (BBB) breakdown, brain edema formation, cognitive disturbances, neuronal damages, and brain pathologies. However, when the pathophysiology of these CNS injuries is aggravated by nanoparticles intoxication or comorbidity factors, adjustment in dosage of nanodrug delivery is needed. This indicates that further research in nanomedicine is needed to explore suitable strategies in achieving greater neuroprotection in CNS injury in combination with nanoparticles intoxication or other comorbidity factors for better clinical practices.
最近,纳米医学的发展使得活性化合物能够通过封装材料或附着在纳米线上靶向递送到中枢神经系统(CNS)。通过任何方式进行纳米药物输送都应该能够增强神经保护作用,因为药物在目标区域内迅速积累,而化合物的代谢速度较慢。这两个因素比传统的药物输送更能增强神经保护作用。然而,目前还不确定纳米药物输送是否会改变化合物的药代动力学,使其更有效,或者仅仅是由于化合物的延长暴露时间,从而导致药物效果增强。我们的实验室致力于理解使用 TiO2 纳米线进行 CNS 损伤模型(例如脊髓损伤(SCI)、高热和/或纳米颗粒中毒)中的纳米药物输送,以及糖尿病或高血压等其他合并症因素对大鼠模型的影响。我们的观察结果表明,纳米线药物输送在 SCI 和高热的正常情况下是有效的,这表现在血脑屏障(BBB)破坏、脑水肿形成、认知障碍、神经元损伤和脑组织病理学的显著减少。然而,当这些 CNS 损伤的病理生理学因纳米颗粒中毒或合并症因素而加重时,需要调整纳米药物输送的剂量。这表明,需要进一步研究纳米医学,以探索在与纳米颗粒中毒或其他合并症因素相结合的情况下,实现 CNS 损伤更大神经保护作用的合适策略,以便更好地应用于临床实践。