Focused ultrasound and microbubbles for enhanced extravasation.
Focused ultrasound and microbubbles for enhanced extravasation.
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DOI：
10.1016/j.jconrel.2010.06.012
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发表时间：
2010-11-20
期刊：
影响因子：
--
通讯作者：
Klibanov AL
中科院分区：
文献类型：
--
作者：
Böhmer MR;Chlon CHT;Raju BI;Chin CT;Shevchenko T;Klibanov AL
血管对白蛋白的渗透性可以通过使用超声波和聚合物或脂质壳微泡来改变。聚焦超声破坏微泡的区域在凝胶体模中量化为压力、循环次数和微泡类型的函数。在 2 MPa 压力下，对于脂质壳试剂，破坏发生在相当宽的区域，而对于聚合物壳试剂，在此设置下，获得了半径仅为 1 mm 的明显破坏点。当使用具有较厚外壳的微气泡时，气泡被破坏的压力会转变为更高的值。在体内，脂质和聚合物微泡均增加了白蛋白结合染料伊文思蓝的外渗，尤其是在肌肉中，导致治疗开始 30 分钟后每克肌肉组织中注射剂量的约 6-8% 外渗，而在没有微泡的情况下，在肌肉中无法检测到伊文思蓝。超声治疗和伊文思蓝注射之间的时间变化表明，在所使用的设置下促进外渗的时间窗口至少为一个小时。在 MC38 肿瘤中，在没有超声的情况下已经发生了外渗，并且只有每克最大注射剂量百分比为 3% 时才能建立约 2 倍的增强趋势。超声介导的微泡破坏尤其增强了 MC38 肿瘤高度血管化的外部和邻近肌肉的外渗，因此对于抗血管生成药物等的释放最有用。
The permeability of blood vessels for albumin can be altered by using ultrasound and polymer or lipid-shelled microbubbles. The region in which the microbubbles were destroyed with focused ultrasound was quantified in gel phantoms as a function of pressure, number of cycles and type of microbubble. At 2 MPa the destruction took place in a fairly wide area for a lipid-shelled agent, while for polymer-shelled agents at this setting, distinct destruction spots with a radius of only 1 mm were obtained. When microbubbles with a thicker shell were used, the pressure above which the bubbles were destroyed shifts to higher values. In vivo both lipid and polymer microbubbles increased the extravasation of the albumin binding dye Evans Blue, especially in muscle leading to about 6–8% of the injected dose to extravasate per gram muscle tissue 30 minutes after start of the treatment, while no Evans Blue could be detected in muscle in the absence of microbubbles. Variation in the time between ultrasound treatment and Evans Blue injection, demonstrated that the time window for promoting extravasation is at least an hour at the settings used. In MC38 tumors, extravasation already occurred without ultrasound and only a trend towards enhancement with about a factor 2 could be established with a maximum percentage injected dose per gram of 3%. Ultrasound mediated microbubble destruction especially enhances the extravasation in the highly vascularized outer part of the MC38 tumor and adjacent muscle and would, therefore, be most useful for release of, for instance, anti-angiogenic drugs.
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作者：
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DOI：
10.1161/01.atv.0000179768.06206.cb
发表时间：
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影响因子：
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