槲皮素纳米脂质体药物的制备及其抗肿瘤作用研究

Preparation and anti-tumor effect of quercetin nano-liposome

目的 制备槲皮素纳米脂质体药物，并对其进行表征，探究槲皮素纳米脂质体药物的体内抗肿瘤作用。方法 以胆固醇和卵磷脂为膜材，采用薄膜-超声法制备槲皮素纳米脂质体药物。采用透射电镜观察所制备槲皮素纳米脂质体粒径及分散度，利用马尔文粒度分析仪测定槲皮素纳米脂质体的Zeta电位。建立宫颈癌荷瘤小鼠模型，探究槲皮素纳米脂质体的抗肿瘤作用，采用尾静脉注射法给小鼠连续注射槲皮素纳米脂质体和原药15 d。测定肿瘤抑制率、胸（脾）脏指数并对肿瘤组织进行病理学观察。结果 磷脂∶胆固醇∶槲皮素＝8∶2∶1，水化时间为15 min，超声时间为15 min，该条件下所制得槲皮素纳米脂质体粒径分布均匀，电位良好；槲皮素纳米脂质体的抑瘤率可达54.16%，显著高于槲皮素原药处理组（χ2＝6.477，P〈0.05）；病理结果显示，槲皮素纳米化后对肿瘤的治疗效果显著优于槲皮素原药处理组。结论 槲皮素原药与槲皮素纳米脂质体均可显著抑制肿瘤生长，且槲皮素纳米化后效果优于槲皮素原药。该研究将为槲皮素纳米脂质体在宫颈癌治疗中的应用提供理论依据和实验基础。

Objective To prepare quercetin liposome and to explore the antitumor effect of quercetin liposome.Methods The cholesterol and lecithin were used as membrane materials,quercetin nano liposome was prepared by thin film ultrasound method.The zeta potential and particle size distribution of quercetin liposome were tested by Malvern laser particle size analyzer and transmission electron microscope respectively.In order to explore the anti-tumor effect of quercetin nano-liposome,the mouse model of cervical cancer was established.After tail vein injection of quercetin and quercetin nano-liposome for 15 days,the tumor inhibitory rate,the thymus（spleen）index were analyzed,and the pathology of tumor tissues was further observed.Results Under the condition of lecithin：cholesterol：quercetin = 8 ：2 ~ 1,the hydration time of 15 min and the ultrasonic time of 15 min,the quercetin nano-liposome was prepared,and the particle size distribution was uniform and the potential was-10.8.The tumor inhibitory rate of quercetin nano-liposome treatment group was 54.16%,which was significantly higher than that of the quercetin treatment group（ X2 = 6.477,P 〈 0.05）.The pathology results of the tumor tissues showed that nanocrystallization of quercetin could increase the anti-cancer effect of quercetin.Conclusion Both quercetin and quercetin nano-liposome exhibit significant effect on the tumor growth,and the inhibitory rate is increased after quercetin was nanocrystallization.Our study will provide theoretical basis for the application of quercetin nano-liposome in the treatment of cervical cancer.