论文部分内容阅读
制备穿心莲内酯(Andrographolide,AP)-甘草酸(glycyrrhizic acid,GA)纳米胶束,以增强穿心莲内酯的溶解性和抗肿瘤效果。首先,以穿心莲内酯为模型药物,甘草酸为载体,制备穿心莲内酯-甘草酸胶束((AP-GA)-PMs),以胶束的粒径、包封率、载药量为指标,考察不同制备方法及载药比对所制备胶束的影响,筛选出最优处方及制备工艺;对最优处方工艺制备的(AP-GA)-PMs的制剂学性质及对肝癌细胞(HepG_2)增殖的抑制作用进行评价。结果表明,最优处方工艺所制备的(AP-GA)-PMs澄清透明呈球形粒径为(127.11±1.38)nm,Zeta电位为(–24.01±0.55)mV,包封率为(92.01±4.02)%,载药量为(51.44±1.24)%,4℃储存30天内稳定,体外释放缓慢、稳定较高。体外细胞毒性结果显示,GA对AP具有协同抗肿瘤作用,同时(AP-GA)-PMs(IC_(50)=19.25μg·mL~(-1))显著增加了AP(IC_(50)=22.40μg·mL~(-1))对HepG_2细胞毒性(P<0.01)。综上,甘草酸作为载体所制备的(AP-GA)-PMs,粒径小,载药量大,稳定性高,并显著提高了AP的抗肿瘤活性。
Preparation of Andrographolide (AP) -glycyrrhizic acid (GA) nanomicelles to enhance the solubility and anti-tumor effect of andrographolide. First, we prepared andrographolide-glycyrrhizic acid micelles (AP-GA) -PMs with andrographolide as model drug and glycyrrhizic acid as carrier, and the particle size, entrapment efficiency and drug loading of micelles The effects of different preparation methods and drug loading ratio on the prepared micelles were investigated, and the optimal formulation and preparation process were screened. The preparation properties of AP-GA- ) Inhibition of proliferation was evaluated. The results showed that the AP-GA-PMs prepared by the optimized formulation showed a clear and transparent spherical particle size of (127.11 ± 1.38) nm and a zeta potential of (-24.01 ± 0.55) mV with an encapsulation efficiency of (92.01 ± 4.02 ), Drug loading was (51.44 ± 1.24)%, stable at 4 ℃ for 30 days, slow release in vitro and high stability. In vitro cytotoxicity results showed that GA had a synergistic anti-tumor effect on AP, and AP (IC 50 = 19.25 μg · mL -1) significantly increased AP (IC 50 = 22.40 μg · mL -1) on HepG_2 cells (P <0.01). In summary, glycyrrhizic acid as a carrier prepared (AP-GA) -PMs, small particle size, drug loading, high stability, and significantly increased the anti-tumor activity of AP.