基于水凝胶微针装载柚皮素的抗肿瘤作用研究

    Study on the Antitumor Effect of Naringenin-loaded Hydrogel Microneedles

    • 摘要:
      目的  利用甲基丙烯酰化明胶(gelatin methacryloyl,GelMA)和聚乙二醇二丙烯酸酯poly(ethylene glycol) diacrylate,PEGDA构建复合水凝胶微针作为柚皮素的递送平台,探讨其抗肿瘤作用。
      方法 通过光交联技术制备复合水凝胶,系统表征其孔隙结构、体外降解特性及药物负载能力。采用CCK-F法探究复合水凝胶的生物相容性;采用CCK-8法评估柚皮素对CT26肿瘤细胞的体外杀伤效果并结合药物释放动力学研究验证微针递送效能。进一步构建小鼠荷瘤模型,通过活体成像及肿瘤体积监测评估载药水凝胶微针的体内抗肿瘤疗效,通过体质量监测和脏器系数分析进行生物安全性验证。
      结果 柚皮素成功装载到复合水凝胶微针中。体外试验显示,微针具有良好的生物安全性,抑制CT26肿瘤细胞活性。体内研究证实,该微针体系抑制肿瘤生长,减小肿瘤体积且未引起小鼠体质量的显著变化,具有良好的抗肿瘤效果和生物安全性。
      结论 本研究构建的GelMA/PEGDA复合水凝胶微针载药体系,有效克服了柚皮素的传统递送缺陷,在结肠癌治疗中展现出优异的抗肿瘤活性。

       

      Abstract:
      OBJECTIVE To fabricate composite hydrogel microneedles as naringenin delivery platforms using gelatin methacryloyl(GelMA) and poly(ethylene glycol) diacrylate(PEGDA), and explore its antitumor effects.
      METHODS The composite hydrogels were prepared by photocrosslinking technology and systematically characterized for their pore structure, in vitro degradation properties and drug loading capacity. The biocompatibility of the composite hydrogels was investigated by the CCK-F method, and the in vitro killing effect of naringenin on CT26 tumor cells was evaluated by the CCK-8 method and combined with drug release kinetics study to validate the efficacy of microneedle delivery. A mouse tumor model was further constructed to evaluate the antitumor efficacy of the drug-loaded hydrogel microneedles in vivo through in vivo imaging and tumor volume monitoring, and the biosafety was verified by body weight monitoring and organ coefficient analysis.
      RESULTS Naringenin was successfully loaded into composite hydrogel microneedles. In vitro experiments showed that the microneedle had good biosafety and inhibited CT26 tumor cell activity. In vivo studies confirmed that the microneedle system inhibited tumor growth and reduced tumor volume without causing significant changes in the body weight of mice, with good antitumor effects and biological safety.
      CONCLUSION The GelMA/PEGDA composite hydrogel microneedle drug delivery system constructed in this study effectively overcomes the traditional delivery defects of naringenin and demonstrated excellent antitumor activity in colon cancer treatment.

       

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