新型和厚朴酚胶束-温敏水凝胶体系防治术后组织粘连作用及机制研究

In 2013, the number of surgeries is more than ten million in China. The incidence of intra-abdominal adhesions is higher than 80% after general surgical abdominal procedures and is even up to 97% after open gynecologic pelvic operations. The anti-adhesion effects of anti-adhesion drugs and barriers used in clinic are disappointed. In our previous experiments, we found that thermosensitive hydrogel had some effects on adhesion prevention. Unfortunately, the anti-adhesion effects of thermosensitive hydrogel was not acceptable in some conditions, such as serious tissue injury and excessive inflammatory exudate. We wonder is it possible to combine the anti-adhesion drug with anti-adhesion barrier by the controlled drug release and barrier characteristics of thermosensitive hydrogel to achieve better anti-adhesion effects in complex conditions. In the present study, honokiol was first incorporated into polymeric micelles using nanotechnology. Then, the drugs incorporated micelles were loaded into thermosensitive hydrogel to form the novel “drug loaded micelles in thermosensitive hydrogel” composite. Subsequently, the composite will be assigned for adhesion prevention test, and the therapeutic effects and mechanisms of adhesion prevention will be investigated indetail. In this study, a novel anti-adhesion composite will be developed for postoperative adhesion prevention, which provided a theoretical basis for synchronous application of anti-adhesion drugs and anti-adhesion barrier. Furthermore, this project is very important on the study of postoperative adhesion prevention.

2013年全国手术量已超过1000万台，80%以上的手术涉及术后粘连问题，盆腔手术粘连发生率更是高达97%。目前临床上使用的各种防粘连药物和阻隔剂，疗效不理想。前期我们发现温敏水凝胶对术后粘连有一定治疗效果，但在组织损伤严重或炎性渗出较多等复杂情况下疗效不佳。我们设想是否可以将水凝胶的药物缓释作用与物理阻隔作用相结合，发挥防粘连药物和防粘连阻隔剂的双重功效，达到在复杂情况下防治术后腹腔粘连的作用。本项目拟在前期工作基础上，采用纳米技术，将和厚朴酚装载于纳米胶束中，然后将载药纳米胶束分散于可生物降解温度敏感型水凝胶中，制备新型“载药纳米胶束-温敏水凝胶”复合体系，重点研究该体系在术后复杂环境下防治术后腹腔粘连的疗效，并阐明其作用机制。通过本项目的研究，将构建一种防治术后粘连的新型复合体系，为防粘连药物-阻隔剂联合应用提供了理论依据和实验基础，对防治术后粘连的研究有重要意义。

目前全国手术量已超过1000万台，80%以上的手术涉及术后粘连问题，盆腔手术粘连发生率更是高达97%。目前临床上使用的各种防粘连药物和阻隔剂，疗效不理想。前期我们发现温敏水凝胶对术后粘连有一定治疗效果，但在组织损伤严重或炎性渗出较多等复杂情况下疗效不佳。我们设想是否可以将水凝胶的药物缓释作用与物理阻隔作用相结合，发挥防粘连药物和防粘连阻隔剂的双重功效，达到在复杂情况下防治术后腹腔粘连的作用。本项目拟在前期工作基础上，采用纳米技术，将和厚朴酚装载于纳米胶束中，然后将载药纳米胶束分散于可生物降解温度敏感型水凝胶中，制备新型“载药纳米胶束-温敏水凝胶”复合体系，重点研究该体系在术后复杂环境下防治术后腹腔粘连的疗效，并阐明其作用机制。本项进展顺利，已经完成了载体材料的合成表征、载药纳米胶束的制备、载药胶束-温敏水凝胶复合体系的构建、二次粘连模型的建立和粘连防治效果评价、复合体系中和厚朴酚体内代谢研究、复合体系的体内外安全性评价、复合体系对创面的贴附效果和降解过程和粘连防治机理研究。结果表明，我们成功制备了“载药纳米胶束-温敏水凝胶”复合体系，该复合体系在常温下为可流动可注射溶胶态。当温度升高至体温，体系转变为不可流动的凝胶态，可以附着于创面起到阻隔作用，同时可以缓慢释放所包载的药物。在大鼠粘连松解术后二次粘连模型中，“载药纳米胶束-温敏水凝胶”复合体系对二次粘连具有较好的治疗效果，可以显著降低粘连发生率，且无明显毒副作用。