Abstract：
To address the adverse side effects associated with systemic high-dose methylprednisolone (MP) therapy for acute spinal cord injury (SCI), we have developed a N-2-hydroxypropyl methacrylamide copolymer-based MP prodrug nanomedicine (Nano-MP). Intravenous Nano-MP selectively targeted to the inflamed SCI lesion and significantly improved neuroprotection and functional recovery after acute SCI. In the present study, we comprehensively assessed the potential adverse side effects associated with the treatment in the SCI rat models, including reduced body weight and food intake, impaired glucose metabolism, and reduced musculoskeletal mass and integrity. In contrast to free MP treatment, intravenous Nano-MP after acute SCI not only offered superior neuroprotection and functional recovery but also significantly mitigated or even eliminated the aforementioned adverse side effects. The superior safety features of Nano-MP observed in this study further confirmed the clinical translational potential of Nano-MP as a highly promising drug candidate for better clinical management of patients with acute SCI.
摘要：
为了解决与全身大剂量甲基强的松龙（MP）治疗急性脊髓损伤（SCI）相关的不良副作用，我们开发了基于N-2-羟丙基甲基丙烯酰胺共聚物的MP前药纳米药物（Nano-MP）。静脉Nano-MP选择性靶向炎症SCI病变，并显着改善急性SCI后的神经保护和功能恢复。在本研究中,我们在SCI大鼠模型中全面评估了与治疗相关的潜在不良副作用，包括减少体重和食物摄入量，葡萄糖代谢受损，减少肌肉骨骼质量和完整性。与游离MP治疗相反，急性SCI后静脉注射Nano-MP不仅提供了优越的神经保护和功能恢复，而且还显着减轻甚至消除了上述不良副作用。在这项研究中观察到的Nano-MP的优越的安全性特征进一步证实了Nano-MP的临床转化潜力，它是一种非常有希望的药物候选药物，可以更好地治疗急性SCI患者。
