荷载甘草酸EL100-55/PLGA肠溶纳米粒的制备及其对葡聚糖硫酸钠诱导结肠炎的治疗作用

Preparation of glycyrrhizic acid-loaded EL100-55/PLGA enteric nanoparticles and evaluation of their effect on dextran sodium sulfate induced ulcerative colitis

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) m V. 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.