Neuroprotective macromolecular methylprednisolone prodrug nanomedicine prevents glucocorticoid-induced muscle atrophy and osteoporosis in a rat model of spinal cord injury

IF 4.2 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Nanomedicine : nanotechnology, biology, and medicine Pub Date : 2024-07-02 DOI:10.1016/j.nano.2024.102773

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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.

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具有神经保护作用的大分子甲基强的松龙原药纳米药物可防止糖皮质激素诱导的脊髓损伤大鼠肌肉萎缩和骨质疏松症。

为了解决急性脊髓损伤（SCI）全身大剂量甲基强的松龙（MP）治疗的副作用，我们开发了一种基于 N-2-羟丙基甲基丙烯酰胺共聚物的 MP 原药纳米药物（Nano-MP）。静脉注射 Nano-MP 可选择性地靶向 SCI 炎症病灶，显著改善急性 SCI 后的神经保护和功能恢复。在本研究中，我们全面评估了与 SCI 大鼠模型治疗相关的潜在不良副作用，包括体重和食物摄入量减少、糖代谢受损、肌肉骨骼质量和完整性降低。与游离 MP 治疗相比，急性 SCI 后静脉注射 Nano-MP 不仅能提供出色的神经保护和功能恢复，还能显著减轻甚至消除上述不良副作用。这项研究中观察到的纳米MP的卓越安全性进一步证实了纳米MP的临床转化潜力，它是一种极具潜力的候选药物，可更好地用于急性脊髓损伤患者的临床治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nanomedicine : nanotechnology, biology, and medicine 工程技术-纳米科技

CiteScore

11.10

自引率

0.00%

发文量

133

审稿时长

42 days

期刊介绍： The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine. Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.