叶酸修饰的粉防己碱壳聚糖纳米粒制备工艺的研究

Study on preparation technology of tetrandrine chitosan nanoparticles modified with folic acid

目的:研究叶酸修饰的粉防己碱(tetrandrine,TET)壳聚糖纳米粒(TET/FA-CSO-NPs)的最佳制备工艺并进行质量评价。方法:以离子交联法制备TET/FA-CSO-NPs,通过单因素及正交试验优化处方组成并确定最佳制备工艺,通过形态观察、粒径、载药量及包封率的考察对其进行质量评价。以MTT法分别检测TET和TET/FA-CSO-NPs作用于人肝癌HepG2细胞的增殖抑制作用,并计算半数抑制浓度(IC_(50))。结果:最佳制备工艺为叶酸-壳聚糖偶联物(FA-CSO)1.50 mg·mL^(-1),TPP浓度2.50 mg·mL^(-1),载药质量比为1∶1,制备的TET/FA-CSO-NPs粒径为(214.9±2.1)nm,Zeta电位为(35.2±1.3)mV,包封率为(89.49±1.21)%,载药量为(24.41±0.33)%,外观圆整、均匀。FA-CSO空白纳米粒的质量浓度达到800μg·mL^(-1)时细胞的存活率为(83.08±9.23)%,TET,TET/CSO-NPs和TET/FA-CSO-NPs的IC_(50)值分别为(15.81±0.73),(11.32±1.06),(9.58±0.85)μg·mL^(-1)。结论:叶酸修饰的粉防己碱壳聚糖纳米粒的制备方法简便、可靠,将TET载入纳米粒后可提高其对HepG2细胞的增殖抑制作用。

OBJECTIVE To study the optimal preparation process and quality evaluation of folic acid modified tetrandrine chitosan nanoparticles(TET/FA-CSO-NPS).METHODS The TET/FA-CSO-NPs were prepared by ionic cross-linking method.The particle size,encapsulation efficiency and drug loading were used as indicators.The single factor investigation and orthogonal experimental design were used to optimize the prescription and preparation process.The quality of TET/FA-CSO-NPs was evaluated by morphology,particle size,drug loading,and encapsulation efficiency.MTT method was used to detect the value-added inhibition of TET and TET/FA-CSO-NPs on human liver cancer HepG2 cells respectively.RESULTS The best preparation process was FA-CSO at 1.50 mg·mL^(-1),TPP concentration at 2.50 mg·mL^(-1),and drug loading ratio at 1:1.The quality evaluation results show that the particle size of TET/FA-CSO-NPs was(214.9±2.1)nm,the Zeta potential was(35.2±1.3)mV,the encapsulation rate was(89.49±1.21)%,the drug loading was(24.41±0.33)%,and the appearance was round and uniform.When the mass concentration of blank FA-CSO-NPs reached 800μg·mL^(-1),the cell survival rate was(83.08±9.23)%,and the IC_(50) values of TET,TET/CSO-NPs and TET/FA-CSO-NPs were(15.81±0.73),(11.32±1.06),(9.58±0.85)μg·mL^(-1)respectively,and the value-added inhibition of TET on HepG2 cells was enhanced by loading TET into nanoparticles.CONCLUSION The preparation method of TET/FA-CSO-NPs is simple and reliable.