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盐酸伊立替康纳米胶束制剂耐受性和药效学评价

崔涛, 武卫党, 慈小燕, 李薇, 郭传敏, 徐静, 伊秀林, 刘昌孝

崔涛, 武卫党, 慈小燕, 李薇, 郭传敏, 徐静, 伊秀林, 刘昌孝. 盐酸伊立替康纳米胶束制剂耐受性和药效学评价[J]. 中国药科大学学报, 2019, 50(2): 175-179. DOI: 10.11665/j.issn.1000-5048.20190207
引用本文: 崔涛, 武卫党, 慈小燕, 李薇, 郭传敏, 徐静, 伊秀林, 刘昌孝. 盐酸伊立替康纳米胶束制剂耐受性和药效学评价[J]. 中国药科大学学报, 2019, 50(2): 175-179. DOI: 10.11665/j.issn.1000-5048.20190207
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CUI Tao, WU Weidang, CI Xiaoyan, LI Wei, GUO Chuanmin, XU Jing, YI Xiulin, LIU Changxiao. Evaluation of tolerance and pharmacodynamics of nano-micelle irinotecan formulation[J]. Journal of China Pharmaceutical University, 2019, 50(2): 175-179. DOI: 10.11665/j.issn.1000-5048.20190207
Citation: CUI Tao, WU Weidang, CI Xiaoyan, LI Wei, GUO Chuanmin, XU Jing, YI Xiulin, LIU Changxiao. Evaluation of tolerance and pharmacodynamics of nano-micelle irinotecan formulation[J]. Journal of China Pharmaceutical University, 2019, 50(2): 175-179. DOI: 10.11665/j.issn.1000-5048.20190207
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盐酸伊立替康纳米胶束制剂耐受性和药效学评价

  • 1.

    天津中医药大学

  • 2.

    天津药物研究院新药评价有限公司

  • 3.

    国家纳米科学中心

基金项目: 天津市科技计划资助项目(No.17YFZCSY01170)

Evaluation of tolerance and pharmacodynamics of nano-micelle irinotecan formulation

摘要

    摘要
  • 摘要: 探究盐酸伊立替康纳米胶束制剂相对于市售盐酸伊立替康注射液(商品名:Campto)在耐受性及药效学方面的改善。通过体外细胞毒性试验，比较两种制剂对于结直肠癌细胞COLO205、HT-29、HCT-8和SW480的体外生长抑制作用；构建COLO205荷瘤小鼠模型，尾静脉注射给予两种制剂，考察荷瘤小鼠对两种制剂的最大耐受剂量，进而探索在接近最大耐受剂量给药时，盐酸伊立替康纳米胶束制剂抗肿瘤药效的改善情况。结果显示，两种制剂对于4种结直肠癌细胞体外生长的抑制作用无明显差异；COLO205荷瘤小鼠对于盐酸伊立替康纳米胶束制剂及Campto的最大耐受剂量分别为432.0及276.5 mg/m2；药效试验中，在接近最大耐受剂量的剂量给药时，二者均表现出明显的抗肿瘤药效，其中，盐酸伊立替康纳米胶束制剂高剂量(345.6 mg/m2)的相对肿瘤增殖率及肿瘤湿重抑制率均显著优于Campto的两个给药剂量(177.0和221.2 mg/m2)(P<；0.05)。
    Abstract: This study aimed to investigate the improvement of tolance and pharmacodynamics of nano-micelle irinotecan formulation compared with irinotecan hydrochloride injection(Campto). The toxic effects of the two formulations on colorectal cancer cells COLO205, HT-29, HCT-8 and SW480 were tested in vitro. COLO205 tumor-bearing mouse model was constructed. The two preparations were given via tail vein injection to investigate the maximum tolerance dose(MTD)of tumor-bearing mice to the two preparations, and then to explore the improvement of anti-tumor efficacy of nano-micelle irinotecan formulation near the MTD. The results showed that there was no significant difference in the inhibitory effect of the two formulations on the four colorectal cancer cells in vitro. The MTD of nano-micelle irinotecan formulation and Campto was 432. 0 and 276. 5 mg/m2 respectively. Both of the two formulations showed significant anti-tumor effect in vivo, and the relative tumor proliferation rate and tumor wet weight inhibition rate of nano-micelle irinotecan formulation at high dose(345. 6 mg/m2)were significantly better than those of Campto at two doses(177. 0 and 221. 2 mg/m2)(P< 0. 05).
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    • 参考文献(12)
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  • 刊出日期:  2019-04-24

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