Angiotensin-II regulates dosing time-dependent intratumoral accumulation of macromolecular drug formulations via 24-h blood pressure rhythm in tumor-bearing mice
Angiotensin-II regulates dosing time-dependent intratumoral accumulation of macromolecular drug formulations via 24-h blood pressure rhythm in tumor-bearing mice
复制标题
血管紧张素-II 通过荷瘤小鼠 24 小时血压节律调节给药时间依赖性大分子药物制剂的瘤内积累
DOI：
10.1016/j.bbrc.2017.11.162
复制
发表时间：
2018
影响因子：
3.1
通讯作者：
Ohdo Shigehiro
中科院分区：
文献类型：
--
作者：
Matsunaga Takashi;Matsunaga Naoya;Kusunose Naoki;Ikeda Eriko;Okazaki Hiroyuki;Kakimoto Keisuke;Hamamura Kengo;Koyanagi Satoru;Ohdo Shigehiro
增加药物治疗效果的一种方法是在一天中最有效和/或最佳耐受的时间施用药物。药代动力学和药效学相关基因表达的昼夜变化被证明有助于小分子药物治疗效果的给药时间依赖性差异。然而，尚未详细研究一天中给药时间对高分子量制剂（例如包封在脂质体中的药物）作用的影响。本研究表明，血压节律影响高分子量制剂效应的给药时间依赖性变化。肉瘤180荷瘤小鼠的收缩压显示出明显的24小时振荡。异硫氰酸荧光素标记的牛血清白蛋白（FITC-BSA）（肿瘤血管通透性的指标）的肿瘤内蓄积随一天中的给药时间而变化，与血压昼夜节律相匹配。此外，脂质体包封的奥沙利铂（Lipo-L-OHP）的肿瘤内蓄积随着收缩压的升高而增加。我们的研究结果表明，昼夜血压振荡可能是一个重要的因素，考虑在癌症治疗中的大分子药物和脂质体的给药策略。
One approach to increasing pharmacotherapy effects is administering drugs at times of day when they are most effective and/or best tolerated. Circadian variation in expression of pharmacokinetics- and pharmacodynamics-related genes was shown to contribute to dosing time-dependent differences in therapeutic effects of small molecule drugs. However, influence of dosing time of day on effects of high molecular weight formulations, such as drugs encapsulated in liposomes, has not been studied in detail. This study demonstrates that blood pressure rhythm affects dosing time-dependent variation in effects of high molecular weight formulations. Systolic blood pressure in sarcoma 180-bearing mice showed significant 24-h oscillation. Intratumoral accumulation of fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA), an indicator of tumor vascular permeability, varied with dosing time of day, matching phases of blood pressure circadian rhythm. Furthermore, intratumoral accumulation of liposome-encapsulated oxaliplatin (Lipo-L-OHP) increased with increases in systolic blood pressure. Our findings suggest that circadian blood pressure oscillations may be an important factor to consider in dosing strategies for macromolecular drugs and liposomes in cancer therapy.