Injectable intrathecal delivery system for localized administration of EGF and FGF-2 to the injured rat spinal cord
Injectable intrathecal delivery system for localized administration of EGF and FGF-2 to the injured rat spinal cord
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DOI：
10.1016/j.expneurol.2005.01.030
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发表时间：
2005-07-01
影响因子：
5.3
通讯作者：
Shoichet, MS
中科院分区：
文献类型：
--
作者：
Hamann, MCJ;Tator, CH;Shoichet, MS
应用生长因子（GF）治疗实验性脊髓损伤（SCI）的效果有限。一个原因可能是输送到损伤部位的方式。我们已经开发了一种微创和安全的药物输送系统（DDS），由高浓度的胶原蛋白溶液组成，可以在损伤部位鞘内注射，提供GF的局部输送。使用可注射DDS。将表皮生长因子（EGF）和碱性成纤维细胞生长因子（FGF-2）共同递送到Sprague-Dawley大鼠的蛛网膜下腔中。EGF和FGF-2在受伤和未受伤的动物体内分布进行了监测，免疫组化。虽然EGF和FGF-2在脊髓中的分布的显著差异是明显的，但是与没有DDS的对照动物相比，GF的局部递送导致在病变中心处显著更少的空化，并且在其至少720个完整尾部处。与对照动物相比，在接受GF的动物中，在病变中心处也存在显著更多的白色物质保留。此外，在注射后第14天，与对照相比，GF的递送导致在紧邻病变边缘的头侧和尾侧的中央管中显著更大的室管膜细胞增殖。这些结果表明，可注射DDS提供了将生物活性治疗剂局部递送至受损脊髓的新范例。(c)2005年爱思唯尔公司All rights reserved.
The administration of growth factors (GFs) for treatment of experimental spinal cord injury (SCI) has shown limited benefits. One reason may be the mode of delivery to the injury site. We have developed a minimally invasive and safe drug delivery system (DDS) consisting of a highly concentrated collagen solution that can be injected intrathecally at the site of injury providing localized delivery of GFs. Using the injectable DDS. epidermal growth factor (EGF) and basic fibroblast growth factor (FGF-2) were co-delivered in the subarachnoid space of Sprague-Dawley rats. The in vivo distribution of EGF and FGF-2 in both injured and uninjured animals was monitored by immunohistochemistry. Although significant differences in the distribution of EGF and FGF-2 in the spinal cord were evident, localized delivery of the GFs resulted in significantly less cavitation at the lesion epicenter and for at least 720 full caudal to it compared to control animals without the DDS, There was also significantly more white matter sparing at the lesion epicenter in animals receiving the GFs compared to control animals. Moreover, at 14 days post-injection, delivery of the GFs resulted in significantly greater ependymal cell proliferation in the central canal immediately rostral and caudal to the lesion edge compared to controls, These results demonstrate that the injectable DDS provides a new paradigm for localized delivery of bioactive therapeutic agents to the injured spinal cord. (c) 2005 Elsevier Inc. All rights reserved.