载芍药苷的甘草次酸修饰脂质聚合物杂化纳米粒的理化性质表征及体外靶向性评价

Physicochemical characterization and in vitro targeting validation of glycyrrhetinic acid modified lipid polymer hybrid nanoparticles with paeoniflorin

目的制备载芍药苷的甘草次酸修饰的脂质聚合物杂化纳米粒(GA-LPHNPs-Pae),对其理化性质进行表征并评价体外靶向性。方法采用两步法制备GA-LPHNPs-Pae,进行外观、粒径与分布、电位、包封率、释放度、红外分析及HepG2细胞摄取靶向定性评价。结果所制备的GA-LPHNPs-Pae外观圆整、分布均匀;粒径、多分散指数和Zeta电位分别为(96.98±0.39)nm、(0.104±0.005)、(-13.10±0.26)mV;红外分析可见甘草次酸特征峰;葡聚糖凝胶柱法测得包封率在41.6%~52.3%;24 h内释放速度先快后慢,2~12 h内释放速度显著下降,曲线平缓,12 h后释放缓慢。以FITC作为荧光探针,以50μg·mL^(-1)浓度NPs-Pae和GALPHNPs-Pae分散液与HepG2细胞共孵育,在2 h时,HepG2细胞摄取GA-LPHNPs-Pae明显优于未修饰的NPs-Pae。结论本文所制备的GA-LPHNPs-Pae外观圆整、分布均匀,对水溶性成分芍药苷包封良好,体外释放缓慢,初步验证对HepG2细胞具有靶向亲和作用。

Objective To characterize the physical and chemical properties of lipid polymer hybrid nanoparticles modified with glycyrrhetinic acid(GA-LPHNPs-Pae)and to evaluate its targeting property in vitro.Methods GA-LPHNPs-Pae was prepared by two-step method.The appearance,particle size and distribution,potential,encapsulation rate,and degree of release were evaluated,the characterization of physical-chemical properties by infrared analysis and targeted qualitative evaluation of HepG2 cell uptake were performed.Results The prepared GA-LPHNPs-Pae was round with uniform distribution.The particle size,dispersion index and Zeta potential were(96.98±0.39)nm,(0.104±0.005),and(-13.10±0.26)mV,respectively.The characteristic peaks of glycyrrhetinic acid were observed by infrared analysis.The encapsulation rate was at 41.6%~52.3%by dextran gel column method.The release velocity was first fast and then turned slow within 24 h,and decreased significantly at 2~12 h,with a gentle curve,and extremely slow after 12 h.FITC was used as the fluorescence probe,and HepG2 cells were incubated with NPs-Pae and GA-LPHNPs-Pae dispersion at 50μg·mL^(-1).The uptake of GA-LPHNPs-Pae by HepG2 cells was significantly better than that of the unmodified NPs-Pae at 2 h.Conclusion The GA-LPHNPs-Pae has a round appearance with uniform distribution,good encapsulation of the water-soluble component paeonia paeflorin,and slow release in vitro,which has been preliminarily verified to have a targeted affinity effect on HepG2 cells.