Departments of Radiology and Neurology, Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
J Cereb Blood Flow Metab. 2012 Jun;32(6):983-8. doi: 10.1038/jcbfm.2012.48. Epub 2012 Apr 11.
Minocycline has been proposed as a way to blunt neurovascular injury from matrix metalloproteinases (MMPs) during stroke. However, recent clinical trials suggest that high levels of minocycline may have deleterious side-effects. Here, we showed that very high minocycline concentrations damage endothelial cells via calpain/caspase pathways. To alleviate this potential cytotoxicity, we encapsulated minocycline in liposomes. Low concentrations of minocycline could not reduce tumor necrosis factor α (TNFα)-induced MMP-9 release from endothelial cells. But low concentrations of minocycline-loaded liposomes significantly reduced TNFα-induced MMP-9 release. This study provides proof-of-concept that liposomes may be used to deliver lower levels of minocycline for targeting MMPs in cerebral endothelium.
米诺环素被认为是一种可以减轻中风时基质金属蛋白酶（MMPs）引起的神经血管损伤的方法。然而，最近的临床试验表明，高浓度的米诺环素可能有有害的副作用。在这里，我们表明，非常高浓度的米诺环素通过钙蛋白酶/半胱天冬酶途径损伤内皮细胞。为了减轻这种潜在的细胞毒性，我们将米诺环素包封在脂质体中。低浓度的米诺环素不能减少肿瘤坏死因子 α（TNFα）诱导的内皮细胞中 MMP-9 的释放。但是，低浓度的载有米诺环素的脂质体可显著减少 TNFα 诱导的 MMP-9 释放。这项研究提供了一个概念验证，即脂质体可用于递送较低浓度的米诺环素，以靶向脑内皮细胞中的 MMPs。
