Rehabilitation in Movement Disorders Laboratory, Kazan Federal University, 18 Kremlyovskaya Str., Kazan, 420008, Russian Federation.
Department of Human and Animal Physiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya Str., Kazan, 420008, Russian Federation.
Exp Brain Res. 2021 Feb;239(2):627-638. doi: 10.1007/s00221-020-05974-w. Epub 2021 Jan 2.
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.
局部载体介导的药物给药是治疗急性脊髓损伤 (SCI) 的一种很有前途的方法,因为它可以增强和/或持续向损伤组织输送药物,同时最大限度地减少全身副作用。我们研究了局部应用具有三功能嵌段共聚物的甲泼尼龙琥珀酸酯 (MPS) 的自组装胶束制剂在大鼠 SCI 后的功能恢复和组织药物含量方面的效果,与单独局部和全身应用 MPS 进行了比较。本研究评估了硬膜外刺激在 SCI 急性期诱导的后肢肌肉运动诱发电位幅度的变化以及局部与全身应用 MPS 后慢性期运动的恢复。结果表明,MPS 与 TBC 联合局部给药有利于脊髓感觉运动回路,增加兴奋性。此外,与全身给药相比,这种制剂在改善 SCI 后的运动功能方面更有效。LC-MS/MS 数据显示,与其他治疗方式相比,TBC 载体的使用使治疗后脊髓中的糖皮质激素含量增加了四倍以上。这项研究的结果表明,以混合胶束形式局部用 TBC 治疗急性 SCI 可以通过促进药物积累和脊髓功能恢复来提供更好的治疗效果。