Journal of Controlled Release(2020)[1]
脊髓损伤(SCI)是由机械创伤引起的一种破坏性的神经系统疾病，它会立即引发一系列事件，包括血管改变、自由基形成、离子平衡的破坏、细胞凋亡和炎症反应。这些退行性事件通常伴随着神经元的丧失和轴突的退化，导致进行性组织损伤和功能残疾。在过去的几十年里，为了修复受损的组织和加速功能恢复，许多药物治疗在脊髓损伤的动物模型中得到了检验。在药物干预中，可能由于只针对复杂损伤的一个方面，只有少数药物可以转化到临床上。
近日，伊朗塞姆南大学新科学技术学院的Nazemi教授报道了一种由神经保护药物盐酸米诺环素(MH)和神经再生药物紫杉醇(PTX)组成的双重给药系统，促进大鼠脊髓半横断损伤模型的组织再生。为此，将PTX包裹的聚乳酸-乙醇酸(PLGA)微球与MH一起引入到海藻酸盐水凝胶中。MH和PTX从海藻酸盐水凝胶中的释放持续时间超过8周。将所获得的水凝胶与空白水凝胶(不含任何药物)一起加载到脊髓损伤后的损伤部位(急性期)。组织学评估显示，双药治疗在七天后减轻了炎症。此外，在接受双药给药系统治疗的大鼠28天后，观察到瘢痕组织减少，神经元再生增加。随着时间的推移，与其他实验组相比，接受双重药物治疗的动物的功能得到了快速和持续的改善。
Spinal cord injury (SCI) is a devastating neurological disorder caused by mechanical trauma and immediately triggers a cascade of events including vascular changes, free radical formation, and disruption of ionic balance, apoptosis and inflammatory response. These degenerative events are usually accompanied by the loss of neurons and axonal degeneration leading to progressive tissue damage and functional disability. Over the past decades, many drug treatments have been examined in animal models of SCI in order to repair the damaged tissue and expedite functional recovery. Among pharmaceutical interventions, only a few of them could be translated into the clinic possibly due to targeting only one aspect of the complicated injury.
Recently, Professor Nazemi from Faculty of New Sciences and Technologies, Semnan University, Semnan, Iran designed a dual-delivery system consisting of a neuroprotective drug, minocycline hydrochloride (MH), and a neuroregenerative drug, paclitaxel (PTX), to enhance tissue regeneration in a rat hemisection model of SCI. For this purpose, PTX-encapsulated poly (lactic-coglycolic acid) PLGA microspheres along with MH were incorporated into the alginate hydrogel. A prolonged and sustained release of MH and PTX from the alginate hydrogel was obtained over eight weeks. The obtained hydrogels loaded with a combination of both drugs or each of them alone, along with the blank hydrogel (devoid of any drugs) were injected into the lesion site after SCI (at the acute phase). Histological assessments showed that the dual-drug treatment reduced inflammation after seven days. Moreover, a decrease in the scar tissue, as well as an increase in neuronal regeneration was observed after 28 days in rats treated with dual-drug delivery system. Over time, a fast and sustained functional improvement was achieved in animals that received dual-drug treatment compared with other experimental groups.
贠智赫
【1】 Z. Nazemi, M. S. Nourbakhsh, S. Kiani, Y. Heydari, M. K. Ashtiani, H. Daemi, H. Baharvand, Journal of controlled release : official journal of the Controlled Release Society 2020, 321, 145.