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首页> 外文期刊>International Journal of Pharmaceutics >Development of an ultrasound sensitive oxygen carrier for oxygen delivery to hypoxic tissue
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Development of an ultrasound sensitive oxygen carrier for oxygen delivery to hypoxic tissue

机译:用于向缺氧组织供氧的超声敏感氧载体的开发

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摘要

Radiation therapy is frequently used in the treatment of malignancies, but tumors are often more resistant than the surrounding normal tissue to radiation effects, because the tumor microenvironment is hypoxic. This manuscript details the fabrication and characterization of an ultrasound-sensitive, injectable oxygen microbubble platform (SE61(O2)) for overcoming tumor hypoxia. SE61(O2) was fabricated by first sonicating a mixture of Span 60 and water-soluble vitamin E purged with perfluorocarbon gas. SE61(O2) microbubbles were separated from the foam by flotation, then freeze dried under vacuum to remove all perfluorocarbon, and reconstituted with oxygen. Visually, SE61(O2) microbubbles were smooth, spherical, with an average diameter of 3.1 mu m and were reconstituted to a concentration of 6.5 E7 microbubbles/ml. Oxygen-filled SE61(O2) provides 16.9 +/- 1.0 dB of enhancement at a dose of 880 mu l/l (5.7 E7 microbubbles/l) with a half-life under insonation of approximately 15 min. In in vitro release experiments, 2 ml of SE61(O2) (1.3 E8 microbubbles) triggered with ultrasound was found to elevate oxygen partial pressures of 100 ml of degassed saline 13.8 mmHg more than untriggered bubbles and 20.6 mmHg more than ultrasound triggered nitrogen-filled bubbles. In preliminary in vivo delivery experiments, triggered SE61(O2) resulted in a 30.4 mmHg and 27.4 mmHg increase in oxygen partial pressures in two breast tumor mouse xenografts. (C) 2014 Elsevier B.V. All rights reserved.
机译:放射疗法通常用于治疗恶性肿瘤,但是由于肿瘤微环境缺氧,因此肿瘤通常比周围的正常组织对放射效应更具抵抗力。该手稿详细介绍了用于克服肿瘤缺氧的超声敏感,可注射氧气微泡平台(SE61(O2))的制造和表征。 SE61(O2)的制造方法是先对Span 60和用全氟化碳气体吹扫的水溶性维生素E的混合物进行超声处理。通过浮选将SE61(O2)微泡从泡沫中分离出来,然后在真空下冷冻干燥以除去所有的全氟化碳,并用氧气复溶。视觉上,SE61(O2)微泡是光滑的球形,平均直径为3.1微米,并重新配制为6.5 E7微泡/ ml的浓度。充满氧气的SE61(O2)以880μl/ l的剂量(5.7 E7微泡/ l)提供16.9 +/- 1.0 dB的增强作用,在声波作用下的半衰期约为15分钟。在体外释放实验中,发现用超声波触发的2 ml SE61(O2)(1.3 E8微气泡)可将100 ml脱气盐水的氧气分压提高到比未触发的气泡高13.8 mmHg,比通过超声波触发的氮气填充高20.6 mmHg。气泡。在初步的体内递送实验中,触发的SE61(O2)导致两个乳腺肿瘤小鼠异种移植物中的氧分压分别增加了30.4 mmHg和27.4 mmHg。 (C)2014 Elsevier B.V.保留所有权利。

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