Deformable gas-filled microbubbles targeted to P-selectin
Deformable gas-filled microbubbles targeted to P-selectin
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DOI：
10.1016/j.jconrel.2006.06.008
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发表时间：
2006-09-12
影响因子：
10.8
通讯作者：
Klibanov, Alexander L.
中科院分区：
文献类型：
--
作者：
Rychak, Joshua J.;Lindner, Jonathan R.;Klibanov, Alexander L.
超声造影微泡已成功靶向许多血管内疾病标志物。我们假设，通过使微泡可变形，导致微泡与内皮细胞粘附接触面积增加和粘附稳定，可以进一步改善靶向递送。活化的白细胞利用这种策略;它们在与脉管系统中的发炎内皮结合后变形。脂质壳微泡靶向内皮炎性蛋白P-选择素与连接到微泡壳的单克隆抗P-选择素抗体。可变形的微泡是通过控制加压与部分气体损失，这产生了一个平均过剩的壳表面积类似于30%，并形成向外突出的皱纹和褶皱。在剪切流下，在平行板流动室中评估目标微泡粘附性和变形性。在0.4和1.35 dyn/cm（2）之间的壁面剪切应力下，可变形微泡的持续粘附始终优于无摩擦微泡的粘附。在此剪切范围内，目标褶皱微泡因剪切流动而变形，这与无褶皱微泡不同。在小鼠提睾肌炎症模型中，通过活体显微镜观察到可变形微泡靶向的显著改善。总的来说，粘附的机械方面，如颗粒形状，可变形性和表面微观结构，是重要的工程有效的位点靶向的基于颗粒的药物用于医学成像和治疗。(c)2006 Elsevier B. V.保留所有权利。
Ultrasound contrast microbubbles have been successfully targeted to a number of intravascular disease markers. We hypothesized that targeted delivery could be improved further, by making the microbubbles deformable, leading to increased microbubble-endothelium adhesion contact area and stabilized adhesion. Activated leukocytes utilize such strategy; they deform after binding to inflamed endothelium in the vasculature. Lipid-shell microbubbles were targeted to the endothelial inflammatory protein P-selectin with a monoclonal anti-P-selectin antibody attached to the microbubble shell. Deformable microbubbles were created by controlled pressurization with partial gas loss, which generated an average excess shell surface area of similar to 30% and the formation of outward-projected wrinkles and folds. Targeted microbubble adhesion and deformability were assessed in the parallel plate flow chamber under shear flow. Sustained adhesion of deformable microbubbles at wall shear stresses between 0.4 and 1.35 dyn/cm(2) was consistently better than adhesion of wrinkle-free microbubbles. Over this shear range, targeted wrinkled microbubbles were deformed by shear flow, unlike wrinkle-free microbubbles. In a murine cremaster inflammation model, a significant improvement of deformable microbubble targeting was observed by intravital microscopy. Overall, the mechanical aspects of adhesion, such as particle shape, deformability and surface microstructure, are important in engineering efficient site-targeted particle-based agents for medical imaging and therapy. (c) 2006 Elsevier B.V. All rights reserved.