三七总皂苷复合纳米囊泡的理化性质及对大鼠心肌缺血的保护作用

Physicochemical Property and Protective Effect on Acute Myocardial Ischemia in Rats of Panax notoginseng Saponins-Loaded Complex Nano Vesicles

目的构建以聚乙二醇单甲醚-聚乳酸共聚物(MPEG-PLGA)纳米粒为核心的三七总皂苷复合纳米囊泡(PNS-CNV),对该复合纳米囊泡的理化性质及对大鼠急性心肌缺血损伤的保护作用进行考察。方法采用复乳-溶剂挥发法制备不同相对分子质量的聚乙二醇单甲醚-聚乳酸共聚物三七总皂苷纳米粒(PNS-NP),以三七总皂苷纳米粒为核心,采用薄膜分散法对其进行包封,制备三七总皂苷复合纳米囊泡;采用超滤法、透射电镜、纳米粒度仪,测定三七总皂苷复合纳米囊泡各指标成分的包封率及其理化性质;建立大鼠急性心肌缺血模型,考察三七总皂苷复合纳米囊泡对心肌及血清中生化指标的影响。结果聚乙二醇单甲醚-聚乳酸共聚物的相对分子质量对三七总皂苷复合纳米囊泡的包封率、粒径及Zeta电位没有显著性影响。药效结果显示,与三七总皂苷水溶液组相比,三七总皂苷复合纳米囊泡组大鼠心肌组织中SOD活力显著提高、H2O2及丙二醛含量降低,血清中乳酸脱氢酶(LDH)活力降低(P<0.05),并且以相对分子质量5000的聚乙二醇单甲醚-聚乳酸共聚物为载体的三七总皂苷复合纳米囊泡的保护作用最优。结论复合纳米囊泡作为三七总皂苷的口服给药传递系统,应用前景广泛。

OBJECTIVE To prepare Panax notoginseng saponins-loaded complex nano vesicles （PNS-CNV） with MPEG-PLGA nanoparticles as the core and investigate the physicochemical property of PNS-CNV and protective action on acute myocardial ischemia in rats. METHODS Double emulsification-solvent evaporation method was used to prepare Panax notoginseng saponins-loaded nano- particles using different molecular weight MPEG-PLGA （PNS-NP）. Thin-film hydration method was applied to entrap PNS-NP as the core to form PNS-CNV. Uhrafihration, transmission electron microscope, dynamic light scattering and electrophoretic light scattering were employed to study the entrapment efficiency of each index component in PNS and physicochemical parameters of PNS-CNV. Acute myocardial ischemia model in rats was established to investigate the protective effect of PNS-CNV. RESULTS The molecular weight of MPEG-PLGA did not affect the entrapment efficiency, particle size and Zeta potential of PNS-CNV. The pharmacodynamic experiment indicated that comparing with PNS solution group, the SOD activity of rat myocardium in PNS-CNV group was elevated with markedly decreased H202, MDA and serum LDH activity （P 〈 0. 05）. The protective effect of PNS-CNV with MPEGS000-PLGA was the most significant. CONCLUSION CNV may be used as potential new oral drug delivery carriers.