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（LMW-CTS-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（M_W）。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（P_app，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P_app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P_app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 (P_app, AB→BL) of PNS was less than 1×10^-6 cm/s, indicating a poor permeability. In LMW-CTS group, the P_app 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.

R283.6

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）