裸鼠乳腺癌模型评价拉帕替尼固体分散体的药效  

Evaluation of Pharmacodynamics of Lapatinib Solid Dispersion in Nude Mice with Breast Cancer

作　　者：胡献跃 戴关海[2] 王晨霞[1] HU Xianyue;DAI Guanhai;WANG Chenxia(Jinhua Polytechnic,Jinhua,Zhejiang,China 321017;Zhejiang Academy of Traditional Chinese Medicine,Hangzhou,Zhejiang,China 310007)

机构地区：[1]金华职业技术学院,浙江金华321017 [2]浙江省中医药研究院,浙江杭州310007

出　　处：《中国药业》2020年第1期11-14,共4页China Pharmaceuticals

基　　金：浙江省公益技术应用研究(实验动物)资助项目[2017C37169]

摘　　要：目的利用裸鼠乳腺癌模型评价拉帕替尼固体分散体的抑瘤效果。方法采用溶剂挥发法,制备不同表观溶解度的甲苯磺酸拉帕替尼固体分散体,建立裸鼠乳腺癌模型,设置模型组、TYKERB对照组、低水溶性组、中水溶性组和高水溶性组,分别灌胃给药6周,比较各组的肿瘤增殖率、抑瘤率、表皮生长因子受体(EGFR)和人表皮生长因子受体2(HER2)蛋白表达量,评价药物表观溶解度的改善与抑瘤作用的关系。结果拉帕替尼表观溶解度的增加与其抑瘤效应成正相关,高水溶性组和中水溶性组与TYKERB对照组比较,肿瘤增殖率、抑瘤率、EGFR和HER2蛋白表达量等指标均有显著改善(P <0. 05)。结论固体分散技术能显著提高甲苯磺酸拉帕替尼的表观溶解度和抑瘤作用。Objective To evaluate the antitumor effect of lapatinib solid dispersion( SD) using nude mice model with breast cancer. Methods Lapatinib ditosylate SDs with different apparent solubility were prepared by solvent evaporation. A model of transplanted tumors of nude mice was established. The mice were treated orally with TYKERB,low water-soluble SD,medium water-soluble SD,high water-soluble SD and water for 6 weeks. The relationship between the apparent solubility of the drug and the antitumor effect was evaluated by comparing the tumor proliferation rate,tumor inhibition rate,the expression of EGFR and HER2 protein. Results The increase of apparent solubility of lapatinib was positively correlated with its antitumor effect. Compared with the TYKER control group,the expression of EGFR and HER2 in the high water-soluble group and the medium water-soluble group were significantly improved( P < 0. 05). Conclusion Solid dispersion technology can significantly improve the apparent solubility and antitumor effect of lapatinib ditosylate.

关 键 词：甲苯磺酸拉帕替尼 移植瘤 表皮生长因子受体 人表皮生长因子受体2 抑瘤率 

分 类 号：R965[医药卫生—药理学] R979.1[医药卫生—药学]