Jimenez Hamann Maria C, Tsai Eve C, Tator Charles H, Shoichet Molly S
Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, Canada.
Exp Neurol. 2003 Aug;182(2):300-9. doi: 10.1016/s0014-4886(03)00040-2.
A novel, localized method for potential delivery of therapeutic agents to the injured spinal cord was investigated. The strategy consists of a polymeric drug solution that gels after injection into the subarachnoid space (SAS). By dispersing therapeutic agents in the polymeric solution, a method is provided for localized delivery to the spinal cord. To determine whether intrathecal injection of this drug delivery system (DDS) would affect cerebrospinal fluid (CSF) flow, a spinal canal model was built using dimensional analysis. Blocking up to 52% of the modeled subarachnoid space of the spinal canal caused minimal pressure differences (9.22 +/- 1.45 Pa), suggesting that implantation of a DDS would not subject the spinal cord to increased pressure. The safety of the DDS was also assessed in vivo by injecting collagen into the SAS of Sprague Dawley rats. Controls received injections of artificial CSF (aCSF). Collagen or aCSF was injected at the T2-T3 spinal level of both uninjured rats and rats injured with a 20g compression clip. The injected collagen persisted in the SAS for at least 8 weeks post-implantation and did not elicit an inflammatory reaction in either uninjured or injured animals. Long-term functional behavior was evaluated with the Basso, Beattie, and Bresnahan (BBB) scale weekly for 8 weeks. Functional behavior was similar in the collagen and aCSF groups, also indicating that the DDS was safe. This minimally invasive DDS may provide an alternative, safe method to deliver therapeutic agents intrathecally.
研究了一种将治疗剂潜在递送至损伤脊髓的新型局部方法。该策略包括一种聚合物药物溶液，其在注入蛛网膜下腔（SAS）后会凝胶化。通过将治疗剂分散在聚合物溶液中，提供了一种将其局部递送至脊髓的方法。为了确定鞘内注射这种药物递送系统（DDS）是否会影响脑脊液（CSF）流动，使用量纲分析构建了一个椎管模型。阻塞高达52%的模拟椎管蛛网膜下腔仅产生最小的压力差（9.22±1.45 Pa），这表明植入DDS不会使脊髓承受压力增加。还通过向Sprague Dawley大鼠的SAS中注射胶原蛋白在体内评估了DDS的安全性。对照组注射人工脑脊液（aCSF）。在未受伤大鼠和用20g压迫夹损伤的大鼠的T2-T3脊髓水平注射胶原蛋白或aCSF。植入后，注射的胶原蛋白在SAS中持续至少8周，并且在未受伤或受伤的动物中均未引发炎症反应。使用Basso、Beattie和Bresnahan（BBB）量表每周评估8周的长期功能行为。胶原蛋白组和aCSF组的功能行为相似，这也表明DDS是安全的。这种微创DDS可能提供一种替代的、安全的鞘内递送治疗剂的方法。
