Evaluation of the targeted delivery of 5-fluorouracil and ascorbic acid into the brain with ultrasound-responsive nanobubbles
Evaluation of the targeted delivery of 5-fluorouracil and ascorbic acid into the brain with ultrasound-responsive nanobubbles
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DOI：
10.1080/1061186x.2017.1419354
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发表时间：
2017-12
影响因子：
4.5
通讯作者：
Yusuke Miura;Yuki Fuchigami;Masayori Hagimori;Hiroki Sato;Koki Ogawa;C. Munakata;M. Wada;K. Maruyama;S. Kawakami
中科院分区：
文献类型：
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作者：
Yusuke Miura;Yuki Fuchigami;Masayori Hagimori;Hiroki Sato;Koki Ogawa;C. Munakata;M. Wada;K. Maruyama;S. Kawakami
摘要 最近，已经开发出使用气泡制剂将超声诱导的药物输送到大脑中。然而，在大脑递送后，缺乏亲水性药物在大脑中的药代动力学信息。在本研究中，为了阐明亲水性药物的时程药代动力学，我们使用了脑微透析方法。使用超声波响应纳米气泡（气泡脂质体（BL））和超声波照射，将两种亲水性药物 5-氟尿嘧啶（5-FU）和抗坏血酸输送到小鼠和大鼠的大脑中，并通过微透析评估它们的时程药代动力学。结果表明，通过检测抗坏血酸的抗氧化能力来评估抗坏血酸的时程药效学支持了时程药代动力学。此外，为了加强我们评估的证据，我们改变了 BL 剂量以及超声照射的持续时间和强度对药物输送的影响。其中，改变BLs剂量时，5-FU脑内迁移趋势与其他报道一致。总之，我们成功地阐明了两种亲水性药物在小鼠和大鼠的脑部递送和超声照射后的时程药代动力学。
Abstract Recently, ultrasound-induced drug delivery into the brain using bubble formulations has been developed. After the brain delivery, however, the information on pharmacokinetics of hydrophilic drugs in the brain is lacking. In this study, to clarify the time-course pharmacokinetics of hydrophilic drugs, we used a brain microdialysis method. Using ultrasound-responsive nanobubbles (bubble liposomes (BLs)) with ultrasound irradiation, two hydrophilic drugs, 5-fluorouracil (5-FU) and ascorbic acid, were delivered into the brain of mice and rats and their time-course pharmacokinetics were evaluated with microdialysis. The results indicated that the time-course pharmacodynamics of ascorbic acid evaluated by examining its antioxidant capacity supported the time-course pharmacokinetics. Additionally, to strengthen the evidences of our evaluation, we varied the effect of BLs dose and duration and intensity of ultrasound irradiation on drug delivery. Among them, when the dose of BLs was changed, the trend of 5-FU intracerebral migration was consistent with other report. In conclusion, we succeeded in clarifying the time-course pharmacokinetics of the two hydrophilic drugs after the brain delivery with bubble formulations and ultrasound irradiation using mice and rats.