Localized carrier-mediated administration of drugs is a promising approach to treatment of acute phase of spinal cord injury (SCI) as it allows enhanced and/or sustained drug delivery to damaged tissues along with minimization of systemic side effects. We studied the effect of locally applied self-assembling micellar formulation of methylprednisolone succinate (MPS) with trifunctional block copolymer of ethylene oxide and propylene oxide (TBC) on functional recovery and tissue drug content after SCI in rats in comparison with local and systemic administration of MPS alone. Variations in the amplitude of motor evoked responses in the hindlimb muscles induced by epidural stimulation during acute phase of SCI and restoration of movements during chronic period after local vs. systemic application of MPS were evaluated in this study. Results demonstrate that local delivery of MPS in combination with TBC facilitates spinal cord sensorimotor circuitry, increasing the excitability. In addition, this formulation was found to be more effective in improvement of locomotion after SCI compared to systemic administration. LC–MS/MS data shows that the use of TBC carrier increases the glucocorticoid content in treated spinal cord by more than four times over other modes of treatment. The results of this study demonstrate that the local treatment of acute SCI with MPS in the form of mixed micelles with TBC can provide improved therapeutic outcome by promoting drug accumulation and functional restoration of the spinal cord.

药物的局部载体介导的给药是治疗急性脊髓损伤（SCI）的有前途的方法，因为它可以增强和/或持续地将药物递送至受损组织，并使全身性副作用降至最低。与局部和全身给药相比，我们研究了局部应用自组装的甲基强的松龙琥珀酸酯（MPS）与环氧乙烷和环氧丙烷的三官能嵌段共聚物（TBC）的自组装胶束制剂对大鼠SCI后功能恢复和组织药物含量的影响。仅MPS。在本研究中，评估了局部或全身应用MPS后，SCI急性期硬膜外刺激引起的后肢肌肉运动诱发反应幅度的变化以及慢性期运动恢复的变化。结果表明，MPS与TBC结合局部给药可促进脊髓感觉运动电路，增加兴奋性。另外，与全身给药相比，发现该制剂在SCI后改善运动方面更有效。LC-MS / MS数据显示，与其他治疗方式相比，使用TBC载体可使治疗脊髓中糖皮质激素含量增加四倍以上。这项研究的结果表明，MPS以TBC混合胶束的形式局部治疗急性SCI可以通过促进药物蓄积和脊髓功能恢复来提供改善的治疗效果。与全身给药相比，发现该制剂在SCI后改善运动方面更有效。LC-MS / MS数据显示，与其他治疗方式相比，使用TBC载体可使治疗脊髓中糖皮质激素含量增加四倍以上。这项研究的结果表明，以MPS与TBC混合的胶束形式局部治疗急性SCI可以通过促进脊髓的药物蓄积和功能恢复来改善治疗效果。与全身给药相比，发现该制剂在SCI后改善运动方面更有效。LC-MS / MS数据显示，与其他治疗方式相比，使用TBC载体可使治疗脊髓中糖皮质激素含量增加四倍以上。这项研究的结果表明，MPS以TBC混合胶束的形式局部治疗急性SCI可以通过促进药物蓄积和脊髓功能恢复来提供改善的治疗效果。