基于水凝胶微针装载柚皮素的抗肿瘤作用研究

Naringenin -Loaded Hydrogel Microneedles for Antitumor Therapy

关键词:  柚皮素  复合水凝胶  抗肿瘤  药物递送  微针

Key words:  naringenin  composite hydrogel  anticancer  drug delivery  microneedle

摘要:

目的 柚皮素具有显著的抗肿瘤药理活性但因其口服生物利用度低、稳定性差致使其在临床应用中受到限制。因此,开发新型药物递送系统以克服其缺陷成为当前研究的重要方向。本研究利用甲基丙烯酰化明胶(GelMA)和聚乙二醇聚己内酯(PEGDA)构建复合水凝胶微针作为柚皮素的递送平台,旨在实现柚皮素的高效靶向递送及抗肿瘤治疗。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,通过体重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。体外实验显示,微针具有良好的生物安全性,明显抑制CT26肿瘤细胞活性。体内研究证实,该微针体系明显抑制肿瘤生长,减少肿瘤体积且未引起小鼠体重的显著变化,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 Naringenin has significant antitumor pharmacological activity but its clinical application is limited by its low oral bioavailability and poor stability. deliverTherefore, the development of novel drug delivery systems to overcome their shortcomings has become an important direction of current research. In this study, we constructed composite hydrogel microneedles using methacrylated gelatin(GelMA) and polyethylene glycol polycaprolactone(PEGDA) as a delivery platform for naringenin, aiming to achieve efficient targeted delivery of naringenin and antitumor therapy. 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 killing effect of naringenin on CT26 tumor cells was evaluated by the CCK-8 method, and the microneedle delivery efficacy was verified by the kinetic study of drug release. A mouse tumor model was further constructed to evaluate the antitumor efficacy of the drug-loaded hydrogel microneedles in vivo by 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 significantly inhibited CT26 tumor cell activity. In vivo studies confirmed that the microneedle system significantly inhibited tumor growth and reduced tumor volume without causing significant changes in the body weight of mice, with good anti-tumor effects and biological safety. CONCLUSION The GelMA/PEGDA composite hydrogel microneedle drug delivery system constructed in this study effectively overcame the traditional delivery defects of naringenin and demonstrated excellent antitumor activity in colon cancer treatment.