Sharma Hari S, Ali Syed, Tian Z Ryan, Patnaik Ranjana, Patnaik S, Lek Per, Sharma Aruna, Lundstedt Torbjörn
Laboratory of Cerebrovascular Research, Department of Surgical Sciences, Anaesthesiology and Intensive Care Medicine, University Hospital, Uppsala University, SE-75185 Uppsala, Sweden.
J Nanosci Nanotechnol. 2009 Aug;9(8):5014-37. doi: 10.1166/jnn.2009.gr04.
Recently nano-drug delivery to the central nervous system (CNS) has been shown to be more effective than the parent compound by itself. An increased availability of the drug for longer periods to the brain or spinal cord and/or a decrease in the drug metabolism altogether could lead to potentiation of the pharmacological activity of the nano-delivered compounds. However, it is still unclear whether the nanocarriers used to deliver the drugs may itself has any potential neurotoxic activity. Although, nanodrug-delivery appears to be a quite promising therapeutic tool for the future clinical therapy, its advantages and limitations for the routine use of patients still needs to be elucidated. Our laboratory is engaged to study a plethora of potential neuroprotective novel compounds delivered to the CNS using nanowiring techniques following brain or spinal cord trauma. Our investigations show that nanowired drugs, if delivered locally following spinal cord injury achieve better neuroprotection than the parent compounds. This effect of nano-drug delivery appears to be very selective in nature. Thus, a clear differentiation based on the compounds used for nano-drug delivery can be seen on various pathological parameters in spinal cord injury. These observations suggest that nanowiring may itself do not induce neuroprotection, but enhance the neuroprotective ability of compounds after trauma. This review describes some recent advances in nano-drug delivery to the CNS in relation to novel neuroprotective strategies with special emphasis on spinal cord trauma based on our own observations and recent findings from our laboratory investigations.
最近研究表明,纳米药物递送至中枢神经系统(CNS)比母体化合物本身更有效。药物在更长时间内对脑或脊髓的可用性增加和/或药物代谢的总体减少可能导致纳米递送化合物的药理活性增强。然而,用于递送药物的纳米载体本身是否具有任何潜在的神经毒性活性仍不清楚。尽管纳米药物递送似乎是未来临床治疗中一种非常有前景的治疗工具,但其在患者常规使用中的优点和局限性仍有待阐明。我们实验室致力于研究大量使用纳米布线技术在脑或脊髓创伤后递送至CNS的潜在神经保护新化合物。我们的研究表明,纳米布线药物如果在脊髓损伤后局部递送,比母体化合物具有更好的神经保护作用。纳米药物递送的这种作用在本质上似乎非常具有选择性。因此,基于用于纳米药物递送的化合物,可以在脊髓损伤的各种病理参数上看到明显的差异。这些观察结果表明,纳米布线本身可能不会诱导神经保护作用,但会增强创伤后化合物的神经保护能力。本综述基于我们自己的观察和实验室研究的最新发现,描述了纳米药物递送至CNS在新型神经保护策略方面的一些最新进展,特别强调脊髓创伤。