Preparation and application of minocycline polymer micelle thermosensitive gel in spinal cord injury

IF 4.6 3区材料科学 Q2 CHEMISTRY, MULTIDISCIPLINARY

Nanoscale Advances Pub Date : 2024-09-16 DOI:10.1039/d4na00625a

Jun Gu, Xiaohu Cai, Faisal Raza, Hajra Zafar, Bo Chu, Haitao Yuan, Tianqi Wang, Jiapeng Wang, Xiaojun Feng

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引用次数: 0

Abstract

Neuroprotection is one important approach for 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 sought to incorporate MC into polyethylene glycol (PEG)- poly (lactate-co-glycolic acid) (PGLA) co-polymer to form micelles, and subsequently micellar thermosensitive MC-loaded hydrogel (MCPP-M-gel) for application in rat model of SCI. After incorporation of MC into micellar system (MCPP-M) via thin film hydration method, it was physically characterized using encapsulation rate, zeta potential, polydispersed index (PDI) and particle size. Later, the micelles were developed into MCPP-M-gel and characterized with appropriate physico-mechanical properties. In vitro release testing was evaluated via diffusion method, while cytotoxicity was performed using neural-crest-derived ectoderm mesenchymal stem cells (EMSCs). Regarding results, controlled and prolonged MC release from MCPP-M-gel for 72 h was observed with the hydrogel exhibiting no cytotoxicity to EMSCs at the studied dose. Afterward, MC, MCPP-M, MCPP-M-gel and blank micellar thermosensitive gel were injected into the injured site of SCI rats. Histopathological evaluation demonstrated that MCPP-M-gel improved histological assessments which depicted that MCPP-M-gel could promote neuronal regeneration at the injured site of the SC after 28 days. Immunofluorescence techniques exhibited that MCPP-M-gel increased 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 SC. This experimental work provides foundation for subsequent investigation and application of MCPP-M-gel in SCI models or other disorders of neurons.

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米诺环素聚合物胶束热敏凝胶的制备及在脊髓损伤中的应用

神经保护是治疗脊髓损伤（SCI）的重要方法之一。米诺环素（MC）是一种已知的神经保护剂，已被用于治疗脊髓损伤，但其治疗效果因不稳定和生物利用度低而受到限制。在此，我们试图将 MC 加入聚乙二醇（PEG）-聚（乳酸-共羟基乙酸）（PGLA）共聚物中形成胶束，然后将胶束热敏性 MC 负载水凝胶（MCPP-M-gel）应用于大鼠 SCI 模型。通过薄膜水合法将 MC 加入胶束体系（MCPP-M）后，利用包封率、ZETA 电位、多分散指数（PDI）和粒度对其进行了物理表征。随后，胶束被制成 MCPP-M 凝胶，并具有适当的物理机械性能。体外释放测试是通过扩散法进行评估的，而细胞毒性则是使用神经干细胞衍生的外胚层间充质干细胞（EMSCs）进行的。结果表明，MCPP-M-凝胶可在 72 小时内控制并延长 MC 的释放，在所研究的剂量下，水凝胶对 EMSC 无细胞毒性。随后，将 MC、MCPP-M、MCPP-M-凝胶和空白胶束热敏凝胶注入 SCI 大鼠的受伤部位。组织病理学评估结果表明，MCPP-M-凝胶改善了组织学评估结果，表明 MCPP-M 凝胶可在 28 天后促进 SC 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 SC 损伤部位神经元 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 Nestin 的表达，并降低了神经胶质纤维酸性蛋白（GFAP）的表达。这项实验工作为 MCPP-M 凝胶在 SCI 模型或其他神经元疾病中的后续研究和应用奠定了基础。

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

Nanoscale Advances Multiple-

CiteScore

8.00

自引率

2.10%

发文量

461

审稿时长

9 weeks