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负载盐酸阿霉素的羟基磷灰石玉米醇溶蛋白pH敏感性纳米载体的体内药效学研究

In Vivo Pharmacodynamic Study of Hydroxyapatite/Zein pH-Sensitive Nanocarrier Loaded with Doxorubicin Hydrochloride
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摘要 目的:研究负载盐酸阿霉素(DOX)的羟基磷灰石(HA)/玉米醇溶蛋白(Zein)pH敏感型纳米给药系统(HA/Zein-DOX NPs)对小鼠乳腺癌移植瘤的药效,探讨药物新剂型。方法:体内通过构建Balb/c小鼠乳腺癌移植瘤模型,并随机分成生理盐水对照组、DOX组和HA/Zein-DOX NPs组,每隔3日测量小鼠体重及肿瘤体积。尾静脉注射3周,完整剥离肿瘤组织,称取瘤质量,计算抑瘤率。然后剥取主要脏器(心、肝、脾、肺、肾),通过H&E染色切片观察,评价HA/Zein-DOX NPs的抗肿瘤效果。结果:移植瘤小鼠肿瘤体积变化结果显示HA/Zein-DOX NPs能有效抑制小鼠乳腺肿瘤生长,且HA/Zein-DOX NPs组小鼠存活时间比生理盐水组和DOX组长,DOX组与HA/Zein-DOX NPs组的抑瘤率分别为50.28%和83.24%。H&E切片表明HA/Zein-DOX NPs组的心脏毒性明显降低,其他器官毒性差异不明显。结论:体内抗肿瘤实验表明DOX和HA/Zein-DOX NPs均能抑制肿瘤生长,HA/Zein-DOX NPs能够显著提高抗肿瘤疗效和小鼠存活率,且能明显降低DOX原料药的心脏毒性。 Objective:To study the in vivo pharmacodynamic of doxorubicin hydrochloride(DOX)-loaded hydroxyapatite(HA)/Zein pHsensitive nano drug delivery system(HA/Zein-DOX NPs)for breast cancer transplantation tumors in nude mice,to explore new drug formulations.Methods:Balb/c mice breast cancer xenograft model was constructed in vivo and randomly divided into normal saline control group,DOX group and HA/Zein-DOX NPs group.The body weight and tumor volume of Balb/c mice were measured every 3 days.The tail vein was injected for 3 weeks,the tumor tissue was completely removed,the tumor mass was weighed,and the tumor inhibition rate was calculated.Then the main organs(heart,liver,spleen,lung,kidney)were stripped and the anti-tumor effect of HA/Zein-DOX NPs was evaluated by H&E staining.Results:The tumor volume changes in transplanted mice showed that HA/Zein-DOX NPs had a effectively inhibition of tumor growth,and the survival time of mice in HA/Zein-DOX NPs group was longer than that in saline group and DOX group,DOX group and HA.The tumor inhibition rates of the HA/Zein-DOX NPs group were 50.28%and 83.24%,respectively.H&E sections showed a significant reduction in cardiotoxicity in the HA/Zein-DOX NPs group and no significant difference in other organ toxicity.Conclusion:In vivo anti-tumor experiments show that DOX and HA/Zein-DOX NPs can inhibit tumor growth,HA/Zein-DOX NPs can significantly improve anti-tumor efficacy and mouse survival rate,and can significantly reduce the cardiotoxicity of raw DOX.
作者 查丽琼 王蓓蕾 陈卫东 张彩云 ZHA Li-qiong;WANG Bei-lei;CHEN Wei-dong;ZHANG Cai-yun(College of Pharmacy,Anhui University of Chinese Medicine,Hefei 230012,China;Institute of Pharmaceutics Anhui Academy of Chinese Medicine,Hefei 230012,China)
出处 《江西中医药大学学报》 2020年第4期74-77,86,共5页 Journal of Jiangxi University of Chinese Medicine
基金 国家自然科学基金项目(51303006) 安徽省重大科研基金项目(KJ2018ZD031) 安徽省自然科学基金项目(1408085MH196)。
关键词 盐酸阿霉素 羟基磷灰石/玉米醇溶蛋白pH敏感型纳米载体 Balb/c小鼠乳腺癌移植瘤模型 抗肿瘤 心脏毒性 Doxorubicin Hydrochloride Hydroxyapatite/Zein pH-sensitive Drug Nanocarrier Balb/c Mice Breast Cancer Xenograft Model Anti-tumor Cardiotoxicity
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