载18味党参丸/PLGA静电纺丝纤维膜用于皮肤组织工程

This study will focus on investigating the processing parameters of the fabrication of Tibetan Medicine-18 flavor dangshen pills loaded poly (lactic-co-glycolic acid) / composite nanofibrous membrane by electrospinning, and qualitatively or quantitatively evaluating the effect of this novel Tibetan medicine formulation on normal and non-normal skin seed cells. Based on the analysis of the experimental results, an experimental animal model shall be further establish to explore the application of this Tibetan medicine formulation in skin tissue engineering, which may help to supply a new way of using Tibetan Medicine in clinical application. Fabricating the traditional Tibetan medicine into micro- / nano-scale formulations, is expected to show a better therapeutic effects on non-normal cells at the molecular level, and reduce the side effects of drugs on normal cells, which may alleviate the suffering of patients. This study can promote Chinese traditional Tibetan medicine to be in line with the international medicine market and revitalize the national medical economics, which means that it shall help the Tibetan medicine industry economy with minority regional characteristics to play an important role in driving the overall development of the whole nation. In a word, in this study, under the guidance of Tibetan medical theory and based on the traditional processing technology, we will combine the Tibetan medicine, 18 flavor dangshen pills, with biomedical polymer materials to fabricate a new formulation of Tibetan medicine, a nanofibrous patch, which is hoped to be used as the scaffold materials of skin tissue engineering.

本研究拟采用高压静电纺丝法将PLGA与藏药18味党参丸复合制成载药微纳米电纺纤维膜，定性或定量评价藏药新剂型对正常与非正常皮肤种子细胞的效应。通过对实验结果的分析，进一步建立实验动物模型，初步探索载藏药微纳米纤维膜用于皮肤组织工程领域。在传统藏药的基础上将药物制成微纳米尺度，更好地作用于细胞，在分子水平上发挥疗效，减少药物对正常细胞的副作用，减轻病人的痛苦。推动我国传统藏药与国际医药市场接轨，振兴民族医药经济，用民族地区特色“医药”产业经济带动民族整体环节发展。本课题在藏医理论的指导下，以传统工艺为基础，探索将藏成药18味党参丸与生物医用高分子材料结合，将其剂型改善为贴剂，有望成为皮肤组织工程支架材料。

本研究旨在藏医理论的指导下，以传统工艺为基础，运用先进药物控释方法开发十八味党参丸/生物活性微纳米载体材料新剂型。采用高压静电纺丝法将PLGA、PCL与藏药18味党参丸研磨细粉（EFP）复合制成载药微纳米纤维膜。用扫描电子显微镜对纤维膜进行表面形貌分析；对其力学性能进行测试比较；测试纤维膜的水接触角；对载有不同厂家药物及不同载药量纤维膜进行体外药物释放和体外降解实验，考察释药行为，分析综合性能。结果：1）纤维表面平整光滑，药物包裹在纤维中；纤维直径分布均匀，平均直径600nm。载药纤维膜亲水性好。西藏1 /PLGA纤维膜力学性能良好，具有最佳综合性能，适合用于皮肤修复、组织工程、药物控释领域。2）加入明胶使得纤维直径变小，载体的亲水性提高，药物扩散速率加快，药物释放速率提高。载西藏2 /PLGA 15%时纤维孔隙率大，纤维综合力学性能最佳；载西藏2 /PLGA 30%的纤维膜释药量最多，纤维膜重量变化最快，降解最多。3）西藏1 /PCL纤维中M0.2,H7.5纤维膜的形貌、亲水性、体外释药、细胞增殖、抗氧化应激效果最佳。本研究进一步拓展了载药剂型，采用冷冻干燥法将海藻酸钠与EFP复合制成载药水凝胶。结论：4）青海/海藻酸钠水凝胶中4%浓度的载药水凝胶显示出最大释放量。细胞抗氧化应激等实验证实适当浓度的EFP释放液对调节细胞分泌有关抗氧化的蛋白具有一定的促进作用。糖尿病SD大鼠模型表明载有EFP的皮肤组织工程支架具有一定的促进皮肤修复的作用，可应用于皮肤疾病的修复。