A novel nested liposome drug delivery vehicle capable of ultrasound triggered release of its payload.
A novel nested liposome drug delivery vehicle capable of ultrasound triggered release of its payload.
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DOI：
10.1016/j.jconrel.2011.06.032
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发表时间：
2011-11-07
期刊：
影响因子：
--
通讯作者：
Esener S
中科院分区：
文献类型：
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作者：
Ibsen S;Benchimol M;Simberg D;Schutt C;Steiner J;Esener S
聚焦超声的使用可以是局部突出肿瘤组织的有效方法，并且具体地触发回声药物递送载体的激活，以努力减少全身化疗副作用。在这里，我们展示了一种独特的超声触发车辆的设计和制造方法，其中有效载荷和全氟化碳气体微泡都封装在脂质体的内部水空间内。这种嵌套的脂质壳几何结构既稳定了微泡，又确保了它在空间上足够接近以始终与脂质体膜相互作用。显示内部微泡在暴露于强度为1 - 1.5 MPa的超声时使外部脂质体膜破碎。聚焦超声允许将内部有效载荷释放到组织模型内的局部区域。载体显示出16%的高有效载荷装载效率、在血液中数小时的稳定性和低水平的体外巨噬细胞识别。高速荧光视频呈现了这种车辆与超声波相互作用的第一个光学图像。这种在深层组织的小区域中打开外膜的能力可以提供超出生化靶向的第二水平的空间和时间控制，使得这些颗粒有希望用于体内动物研究。
The use of focused ultrasound can be an effective method to locally highlight tumor tissue and specifically trigger the activation of echogenic drug delivery vehicles in an effort to reduce systemic chemotherapy side effects. Here we demonstrate a unique ultrasound triggered vehicle design and fabrication method where the payload and a perfluorocarbon gas microbubble are both encapsulated within the internal aqueous space of a liposome. This nested lipid shell geometry both stabilized the microbubble and ensured it was spatially close enough to interact with the liposome membrane at all times. The internal microbubble was shown to fragment the outer liposome membrane upon exposure to ultrasound at intensities of 1 - 1.5 MPa. The focused ultrasound allowed the release of the internal payload to localized regions within tissue phantoms. The vehicles showed high payload loading efficiency of 16%, stability in blood of several hours, and low level macrophage recognition in vitro. High speed fluorescent videos present the first optical images of such vehicles interacting with ultrasound. This ability to open the outer membrane in small regions of deep tissue could provide a second level of spatial and temporal control beyond biochemical targeting, making these particles promising for in vivo animal studies.