透明质酸包裹的木犀草素胶束制备及其对小鼠肺癌移植瘤的抑制作用

Preparation of hyaluronic acid-encapsulated luteolin micelles its inhibition on lung cancer xenografts in mice

目的:评估木犀草素胶束经透明质酸包裹后的肿瘤靶向性。方法:采用逆相蒸发法制备透明质酸包裹的木犀草素胶束(HA-LE-MC),以包封率和粒径为优化指标对处方进行筛选,测定其表观形态、载药量、包封率和粒径,最后进行了肺癌移植瘤小鼠活体成像实验与体内抗肿瘤实验。结果:泊洛沙姆407(F127)与双十烷基二甲基溴化铵(DDAB)的最佳质量配比为9∶1,HA-LE-MC粒径为(140.0±1.8)nm,包封率为(61.2±2.4)%,载药量为(74.0±1.2)μg/mL。活体成像实验表明胶束尾静脉注射后集中分布在肿瘤部位,说明胶束具有较强的肿瘤靶向性。体内抗肿瘤实验显示,HA-LE-MC对Lewis肺癌移植瘤有抑制作用,与原料药组相比,小鼠瘤重显著降低(P<0.01),与顺铂相比对体重的影响减小,且能增加荷瘤小鼠的脏器指数。结论:制备的HA-LE-MC具有靶向性,抗肿瘤活性增强,且能增强荷瘤小鼠免疫功能,改善生存状况。

Objective:To prepare luteolin micelles encapsulated by hyaluronic acid and evaluate its inhibition on lung cancer xenografts in mice.Methods:Reverse phase evaporation method was used to prepare hyaluronic acid-coated luteolin micelles(HA-LE-MC).The prescription was screened with encapsulation efficiency and particle size as optimization indicators,and its apparent morphology,drug loa-ding,encapsulation efficiency and particle size were determined and finally in vivo imaging experiments and in vivo anti-tumor experiments.Results:The best mass ratio of poloxamer 407(F127)and didecyl dimethyl ammonium bromide(DDAB)was 9∶1,and the particle size of HA-LE-MC was about(140.0±1.8)nm,the encapsulation rate was(61.2±2.4)%.The drug loading was(74.0±1.2)μg/mL.In vivo imaging experiments showed that micelles were concentrated in the tumor site after tail vein injection,indicating that micelles had strong tumor targeting.In vivo anti-tumor experiments showed that compared with luteolin HA-LE-MC had stronger inhibitory effect on Lewis lung cancer xenograft tumors(P<0.01),and it had lower side effects compared with the positive drug cisplatin(P<0.05),and could enhance the immune function of tumor-bearing mice.Conclusion:The prepared HA-LE-MC had targeted properties,enhanced anti-tumor activity and could enhance the immune function of tumor-bearing mice and improve the survival of mice with explanted lung cancer.