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TN14003壳聚糖温敏型凝胶制剂关节内靶向递药调控骨性关节炎软骨退变研究

批准号81760403 学科分类骨、关节、软组织退行性病变 ( H0609 )
项目负责人李彦林 负责人职称教授 依托单位昆明医科大学
资助金额33.00
万元
项目类别地区科学基金项目 研究期限2018 年 01 月 01 日 至
2021 年 12 月 31 日
中文主题词骨性关节炎;温敏型凝胶;软骨退变;靶向药物;滇南小耳猪
英文主题词osteoarthritis;thermosensitive hydrogel;cartilage degeneration;targeted drug;Diannan small ear pig

摘要

中文摘要 随着社会人口的老龄化,骨性关节炎(OA)患病率日益剧增,我们前期研究表明CXCR4拮抗剂可阻断SDF-1/CXCR4信号通路调控关节软骨退变,而TN14003拮抗效率高、稳定性好、安全性佳。为此提出假说:若将TN14003制成新型温敏智能凝胶关节内靶向递药治疗OA,既提高局部靶向药物疗效,又避免口服制剂首过消除效应及全身应用不良影响。故本研究采用星点-效应面法优化制备TN14003壳聚糖温敏型凝胶,从分子、细胞、组织及滇南小耳猪OA模型体内多层面系统深入研究TN14003壳聚糖温敏型凝胶的理化性质、生物学特性及关节内靶向递药阻断SDF-1/CXCR4信号通路调控OA软骨退变效果及分子机理,经细胞毒性、流式细胞分析、大体观察、软骨组织学观察评分、免疫组化染色、ELISA测定、RT-PCR及Western blot检测,探寻关节内靶向调控OA软骨退变新药,为研发高效安全的OA靶向药物提供依据。
英文摘要 With aging of population in the society, the prevalence rate of osteoarthritis(OA) is growing rapidly.Our previous studies showed that antagonists of CXCR4 could regulate degeneration of articular cartilage by blocking SDF-1/CXCR4 signaling pathway.The TN14003 has the characteristics of higher antagonistic efficiency,well stability and safety.So, we hypothesize that OA can be treated by delivering targeted TN14003 drug in joint if we develop new intelligent thermosensitive hydrogel with TN14003.It could not only improve the local targeted drug efficacy,but also avoid the first pass elimination of oral drug and whole body side effects. Therefore,this study was designed through optimizing TN14003 chitosan thermosensitive hydrogel with central composite design-response surface methodology,its physicochemical properties,biological characteristics,efficacy and molecular mechanism regulating the OA cartilage degeneration by targeted inteligent drug delivery with TN14003 chitosan thermosensitive hydrogel will be systemetic deeply studied at the level of molecule,cell,tissue and Diannan small ear pig OA model in vitro and vivo.The flow cytometry,gross observation,cartilage tissue histological observation and scores,immunohistochemical staining,ELISA detection, RT-PCR and Western blot detection will be used to explore new local targeted drugs for regulating OA cartilage degeneration in joint.This reseach will provide a new experimental basis on developing high efficacy,safety and local targeted drugs for OA treatment.
结题摘要

成果

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