Development of an ultrasound sensitive oxygen carrier for oxygen delivery to hypoxic tissue.
Development of an ultrasound sensitive oxygen carrier for oxygen delivery to hypoxic tissue.
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DOI：
10.1016/j.ijpharm.2014.11.023
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发表时间：
2015-01-15
影响因子：
5.8
通讯作者：
Wheatley MA
中科院分区：
文献类型：
--
作者：
Eisenbrey JR;Albala L;Kramer MR;Daroshefski N;Brown D;Liu JB;Stanczak M;O'Kane P;Forsberg F;Wheatley MA
放射疗法经常用于治疗恶性肿瘤，但肿瘤通常比周围正常组织对放射效应更具抵抗力，因为肿瘤微环境是缺氧的。这份手稿详细介绍了超声波敏感的，可注射的氧气微泡平台（SE 61 O2）的制造和表征，以克服肿瘤缺氧。SE 61 O2是通过首先对Span 60和水溶性维生素E的混合物进行超声处理来制造的，该混合物用全氟化碳气体净化。通过浮选将SE 61 O2微泡与泡沫分离，然后在真空下冷冻干燥以除去所有的全氟化碳，并用氧气重构。目视检查，SE 61 O2微泡光滑、呈球形，平均直径为3.1 μm，复溶后浓度为6.5 E7微泡/ml。充氧SE 61 O2在剂量为880 μl/l（5.7 E7微泡/l）时可提供16.9 ± 1.0 dB的增强，在超声作用下的半衰期约为15 min。在体外释放实验中，发现用超声触发的2 ml SE 61 O2（1.3 E8微泡）使100 ml脱气盐水的氧分压比未触发的气泡高13.8 mmHg，比超声触发的氮气填充的气泡高20.6 mmHg。在初步的体内递送实验中，触发的SE 61 O2导致两个乳腺肿瘤小鼠异种移植物中的氧分压增加30.4 mmHg和27.4 mmHg。
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 (SE61O2) for overcoming tumor hypoxia. SE61O2 was fabricated by first sonicating a mixture of Span 60 and water-soluble vitamin E purged with perfluorocarbon gas. SE61O2 microbubbles were separated from the foam by flotation, then freeze dried under vacuum to remove all perfluorocarbon, and reconstituted with oxygen. Visually, SE61O2 microbubbles were smooth, spherical, with an average diameter of 3.1 μm and were reconstituted to a concentration of 6.5 E7 microbubbles/ml. Oxygen-filled SE61O2 provides 16.9 ± 1.0 dB of enhancement at a dose of 880 μl/l (5.7 E7 microbubbles/l) with a half-life under insonation of approximately 15min. In in vitro release experiments, 2 ml of SE61O2 (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 SE61O2 resulted in a 30.4 mmHg and 27.4 mmHg increase in oxygen partial pressures in two breast tumor mouse xenografts.
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