Gu Jun, Cai Xiaohu, Raza Faisal, Zafar Hajra, Chu Bo, Yuan Haitao, Wang Tianqi, Wang Jiapeng, Feng Xiaojun
School of Medicine, Yangzhou University Yangzhou Jiangsu 225009 China
Department of Orthopedics, Xishan People's Hospital Wuxi Jiangsu 204105 China.
Nanoscale Adv. 2024 Sep 16;6(23):5874-88. doi: 10.1039/d4na00625a.
Neuroprotection is an important approach for the treatment of spinal cord injury (SCI). Minocycline (MC), a known neuroprotective agent, has been utilized for SCI treatment, but its therapeutic effect is limited by instability and low bioavailability. Herein, we developed an innovative micellar thermosensitive hydrogel (MCPP-M-gel) that encapsulates MC in polyethylene glycol (PEG)-poly(lactide--glycolic acid) (PLGA) micelles to enhance its therapeutic efficacy in a rat model of SCI. The micelles were synthesized the thin-film hydration method and characterized for encapsulation efficiency, particle size, zeta potential, and polydispersity index (PDI). MCPP-M-gel demonstrated favorable physico-mechanical properties and extended MC release over 72 hours without cytotoxic effects on neural crest-derived ectoderm mesenchymal stem cells (EMSCs). Thereafter, MC, MCPP-M, MCPP-M-gel and a blank micellar thermosensitive gel were injected into the injured site of SCI rats. Histopathological evaluation demonstrated that MCPP-M-gel could promote neuronal regeneration at the injured site of the SC after 28 days. Immunofluorescence techniques revealed that MCPP-M-gel increased the expression of neuronal class III β-tubulin (Tuj1), myelin basic protein (MBP), growth-associated protein 43 (GAP43), neurofilament protein-200 (NF-200) and nestin as well as reduced glial-fibrillary acidic protein (GFAP) expression in damaged areas of the SC. In conclusion, this study innovatively developed MCPP-M-gel based on a PEG-PLGA copolymer as a biomaterial, laying a solid foundation for further research and application of MCPP-M-gel in SCI models or other neurodegenerative diseases.
神经保护是治疗脊髓损伤（SCI）的重要方法。米诺环素（MC）是一种已知的神经保护剂，已被用于SCI治疗，但其治疗效果受到稳定性和低生物利用度的限制。在此，我们开发了一种创新的胶束热敏水凝胶（MCPP-M-凝胶），它将MC包裹在聚乙二醇（PEG）-聚（丙交酯-乙交酯）（PLGA）胶束中，以增强其在大鼠SCI模型中的治疗效果。通过薄膜水化法合成胶束，并对其包封率、粒径、zeta电位和多分散指数（PDI）进行表征。MCPP-M-凝胶表现出良好的物理机械性能，MC释放时间超过72小时，且对神经嵴衍生的外胚层间充质干细胞（EMSCs）无细胞毒性作用。此后，将MC、MCPP-M、MCPP-M-凝胶和空白胶束热敏凝胶注入SCI大鼠的损伤部位。组织病理学评估表明，28天后MCPP-M-凝胶可促进脊髓损伤部位的神经元再生。免疫荧光技术显示，MCPP-M-凝胶增加了脊髓损伤区域神经元III类β-微管蛋白（Tuj1）、髓鞘碱性蛋白（MBP）、生长相关蛋白43（GAP43）、神经丝蛋白-200（NF-200）和巢蛋白的表达，并降低了胶质纤维酸性蛋白（GFAP）的表达。总之，本研究创新性地开发了基于PEG-PLGA共聚物作为生物材料的MCPP-M-凝胶，为MCPP-M-凝胶在SCI模型或其他神经退行性疾病中的进一步研究和应用奠定了坚实基础。
