低相对分子质量壳聚糖及其纳米粒对三七总皂苷肠道渗透性的影响  

Effects of low molecular weight chitosan and its nanoparticles on intestinal permeability of Panax notoginseng saponins

作　　者：谢振 徐彭[2] 资鹏鹏 徐贤柱[1] 游清徽 王曼莹[1,2] 蔡险峰 XIE Zhen;XU Peng;ZI Peng-peng;XU Xian-zhu;YOU Qing-hui;WANG Man-ying;CAI Xian-feng(Jiangxi Provincial Key Lab of Protection and Utilization of Subtropical Plant Resources,Jiangxi Normal University,Nanchang 330022,China;School of Pharmacy,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China)

机构地区：[1]江西师范大学江西省亚热带植物资源保护与利用重点实验室,江西南昌330022 [2]江西中医药大学药学院,江西南昌330004

出　　处：《中草药》2020年第13期3424-3432,共9页Chinese Traditional and Herbal Drugs

基　　金：国家“重大新药创制”科技重大专项(2018ZX 09721002-008);教育厅成果落地重点项目(GJJ10006)。

摘　　要：目的利用人结直肠腺癌细胞Caco-2细胞模型,考察低相对分子质量壳聚糖(LMW-CTS)及其纳米粒(LMWCTS-NPs)对三七总皂苷(PNS)肠道渗透性的影响。方法采用固相化壳聚糖酶酶解结合超滤分离技术制备LMW-CTS,渗透凝胶色谱法(GPC)测定其相对分子质量(Mw)。离子凝胶法制备LMW-CTS-NPs,并通过扫描电镜、纳米粒度分析和红外光谱进行表征。建立并验证Caco-2细胞模型,评价LMW-CTS和LMW-CTS-NPs对PNS渗透性的影响。结果 LMW-CTS平均均相对分子质量为5 760,多分散系数为1.42。LMW-CTS-NPs形貌圆整,粒度分布窄,平均粒径为115.5 nm,Zeta电位为+37.1 mV。PNS原料药各组分的表观渗透系数(Papp,AP→BL)均小于1×10-6 cm/s;LMW-CTS组中,三七皂苷R1(R1)和人参皂苷Rg1 (Rg1)的Papp分别提高17.83%和20.29%,其他组分则无明显提升;而LMW-CTS-NPs组R1、Rg1、人参皂苷Re (Re)、人参皂苷Rb1 (Rb1)和人参皂苷Rd (Rd)的Papp比对照组分别提高35.66%、23.28%、29.41%、37.99%和36.00%。结论 LMW-CTS可明显促进R1和Rg1的肠道渗透性,但对Re、Rb1和Rd无明显促进作用;而LMW-CTS-NPs显著提高PNS中主要单体皂苷组分的渗透性,进一步改善PNS的肠道通透性。Objective To evaluate the effect of low molecular weight chitosan(LMW-CTS) and its nanoparticles(LMW-CTS-NPs)on the intestinal permeability of Panax notoginseng saponins(PNS) by using Caco-2 cell model.Methods LMW-CTS was prepared by combining chitosanase hydrolysis combined with ultrafiltration separation technology,and molecular weight of LMW-CTS was determined by using permeation gel chromatography(GPC).LMW-CTS-NPs were prepared by ionic gel method,and characterized by scanning electron microscopy,nano particle sizer,and flourier transformation infrared spectroscopy.Caco-2 cell model was established and validated to evaluate the effects of LMW-CTS and LMW-CTS-NPs on the intestinal permeability of PNS.Results LMW-CTS has a molecular weight of 5 760 and a polydispersity coefficient of 1.42.LMW-CTS-NPs have a round shape and narrow particle size distribution,with an average particle size of 115.5 nm and zeta potential of+37.1 mV.The apparent permeability coefficients(Papp,AB→BL) of PNS was less than 1 × 10-6 cm/s,indicating a poor permeability.In LMW-CTS group,the Papp of R1 and Rg1 was increased by 17.83% and 20.29%,respectively,but no significant effect of promotion was observed on other components.However,the Papp of R1,Rg1,Re,Rb1,and Rd in LMW-CTS-NPs group was increased by 35.66%,23.28%,29.41%,37.99%,and 36.00%,respectively,compared tothe control group.Conclusion LMW-CTS can significantly promote the intestinal mucosal permeability of R1 and Rg1 in PNS,but has no significant effect on Re,Rb1,and Rd.LMW-CTS-NPs significantly increased the permeability of the major monomer saponin components in PNS.Namely,the intestinal permeability of PNS can be further improved by transforming LMW-CTS into LMW-CTS-NPs.

关 键 词：低相对分子质量壳聚糖 离子凝胶法 壳聚糖纳米粒 三七总皂苷 CACO-2细胞模型 渗透性 超滤分离 渗透凝胶色谱法 表观渗透系数 三七皂苷R1 人参皂苷Rg1 人参皂苷Re 人参皂苷Rb1 人参皂苷RD 

分 类 号：R283.6[医药卫生—中药学]