香茅醇自乳化递送系统的制备及其体外抗肿瘤活性评价

Preparation of citronellol self-emulsifying delivery system and evaluation of its in vitro antitumor activity

目的考察香茅醇(citronellol,CT)对人喉癌上皮细胞HEp-2和人乳腺癌细胞MCF-7增殖能力的影响,并制备CT自乳化递送系统(self-emulsified drug delivery system,SMs),对HEp-2体外抗肿瘤活性和细胞摄取能力进行评价。方法采用MTT法考察CT对HEp-2和MCF-7细胞增殖能力的影响;通过伪三元相图法优化香茅醇自乳化递送系统(CT-SMs)处方,进行外观形态、粒径和Zeta电位表征。采用MTT法检测CT-SMs对HEp-2细胞增殖能力的影响;荧光倒置显微镜定性和流式细胞仪定量考察HEp-2细胞对CT-SMs的摄取情况。结果经一定质量浓度CT处理后,MCF-7细胞增殖未受影响,差异无统计学意义(与对照组相比,P>0.05),而HEp-2细胞的增殖能力受到明显抑制(与对照组相比,P<0.05),呈剂量-时间依赖性;CT-SMs最佳处方是K_m(乳化剂与助乳化剂比例)为Kolliphor~?HS15-无水乙醇7∶3,CT-Km为3∶7。制备的微乳平均粒径为(354.0±9.5)nm,外观圆整呈类球形,分布均匀,Zeta电位为(-13.4±0.3)m V。细胞摄取实验结果表明,相同质量浓度的CT-SMs和CT处理HEp-2细胞后,CT-SMs较CT摄取量更多,分别为545.70±11.56、230.00±17.76。结论。采用滴加水法成功制备了CT-SMs,其处方工艺可行,制得的自微乳质量稳定可控。CT-SMs可明显抑制HEp-2细胞的增殖。

Objective To investigate the effect of citronellol(citronellol,CT)on the proliferation of HEp-2 and MCF-7 cells,and prepare CT self-emulsifying drug delivery system(CT-SMs).Its antitumor activity and cell uptake ability of HEp-2 cells in vitro was evaluated.Methods The effect of CT on the cell proliferation of HEp-2 and MCF-7 were investigated by MTT assay.The pseudo-ternary phase diagram method was used to optimize the formulation of CT-SMs,and the appearance morphology,mean particle size,and Zeta potential were characterized.The effect of CT-SMs on the proliferation of HEp-2 cells was detected by MTT assay and cellular uptake was determined by fluorescence inversion microscopy and flow cytometry.Results After a certain concentration of CT treatment,MCF-7 cells proliferation was not affected,and the difference was not statistically significant(P>0.05 compared with the control group),while the proliferative capacity of HEp-2 cells was significantly inhibited(P<0.05 compared with the control group)in a dose-time dependent manner.The best prescription for CT-SMs was as following:Km(emulsifier∶co-emulsifier)was Kolliphor?HS 15∶absolute ethanol=7∶3,CT∶Km=3∶7,the mean particle size was(354.0±9.5)nm,the appearance was round and spherical with uniform distribution,and the Zeta potential was(-13.4±0.3)mV.The results of cellular uptake experiments showed that the intake of CT-SMs(545.70±11.56)was higher than that of CT(230.00±17.76)in HEp-2 cells treating the same concentration of CT-SMs and CT.Conclusion CT-SMs could significantly inhibit the proliferation of HEp-2 cells.In this study,CT-SMs were successfully prepared by dropping water method and the quality of CT-SMs was stable and controllable.