目的 制备荷载甘草酸Eudragit L100-55/聚（乳酸-羟基乙酸）共聚物肠溶纳米粒[glycyrrhizic acid loaded Eudragit L100-55/poly （lactic-co-glycolic acid） enteric nanoparticles，GA@EL100-55/PLGA NPs]，并考察其对葡聚糖硫酸钠（dextran sodium sulfate，DSS）诱导结肠炎模型小鼠的治疗作用。方法 采用复乳化溶剂蒸发法制备GA@EL100-55/PLGA NPs，并对其形貌、粒径大小、表面ζ电位等理化性质进行表征；以体质量及结肠长度变化为指标，考察其对DSS诱导的溃疡性结肠炎小鼠的治疗效果。以细胞膜红色荧光染料1，1'-dioctadecyl-3，3，3'，3'-tetramethylindodicarbocyanine，4-chlorobenzenesulfonate salt （DiD）为探针，探讨纳米粒在肠道的滞留情况。结果 GA@EL100-55/PLGA NPs外观呈圆球状，平均粒径为（166.0±3.4） nm，ζ电位为（-7.17±0.22） mV；包封率及载药量分别为（91.51±0.26）%和（5.35±0.01）%。体外释放结果提示，GA@EL100-55/PLGA NPs具有pH值响应特性及缓释效果。药效学实验证明GA@EL100-55/PLGA NPs能够对DSS诱导的溃疡性结肠炎模型小鼠具有保护作用。结论 GA@EL100-55/PLGA NPs为甘草酸在治疗溃疡性结肠炎提供新的递送形式。

Objective To prepare glycyrrhizic acid loaded Eudragit L100-55/poly(lactic-co-glycolic acid) enteric nanoparticles, GA@EL100-55/PLGA NPs, and evaluate their effect on dextran sodium sulfate (DSS) induced ulcerative colitis. Methods GA@EL100-55/PLGA NPs were prepared by double-emulsion and solvent-evaporation method, and their physicochemical properties, such as morphology, particle size distribution as well as ζ potential, were characterized; In light of the changes of body weight and colon length, the therapeutic effect on ulcerative colitis induced by DSS in mice was investigated. The retention of GA@EL100-55/PLGA NPs in the gastrointestinal tract was determined using 1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine,4-chlorobenzenesulfonate salt (DiD) as fluorescent probe. Results The morphology of GA@EL100-55/PLGA NPs were spherical with the average particle size of (166.0 ±3.4) nm and ζ potential of (−7.17 ±0.22) mV. The encapsulation efficiency and drug loadings were (91.51 ±0.26)% and (5.35 ±0.01)%, respectively. The in vitro drug release of GA@EL100-55/PLGA NPs showed pH-responsive and sustained release properties. In addition, pharmacodynamics experiments demonstrated that GA@EL100-55/PLGA NPs had better protection on DSS induced colitis model mice. Conclusion GA@EL100-55/PLGA NPs can provide a novel delivery system of glycyrrhizic acid for treatment of ulcerative colitis disease.

R283.6

山东第一医科大学2021年山东省大学生创新创业训练计划项目（S202110439008）