Jun Gu, Xiaohu Cai, Faisal Raza, Hajra Zafar, Bo Chu, Haitao Yuan, Tianqi Wang, Jiapeng Wang and Xiaojun Feng
{"title":"Preparation of a minocycline polymer micelle thermosensitive gel and its application in spinal cord injury","authors":"Jun Gu, Xiaohu Cai, Faisal Raza, Hajra Zafar, Bo Chu, Haitao Yuan, Tianqi Wang, Jiapeng Wang and Xiaojun Feng","doi":"10.1039/D4NA00625A","DOIUrl":null,"url":null,"abstract":"<p >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-<em>co</em>-glycolic acid) (PLGA) micelles to enhance its therapeutic efficacy in a rat model of SCI. The micelles were synthesized <em>via</em> 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 <em>in vitro</em> 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.</p>","PeriodicalId":18806,"journal":{"name":"Nanoscale Advances","volume":" 23","pages":" 5874-5888"},"PeriodicalIF":4.6000,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/na/d4na00625a?page=search","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nanoscale Advances","FirstCategoryId":"88","ListUrlMain":"https://pubs.rsc.org/en/content/articlelanding/2024/na/d4na00625a","RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
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-co-glycolic acid) (PLGA) micelles to enhance its therapeutic efficacy in a rat model of SCI. The micelles were synthesized via 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 in vitro 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.