Tartis Michaelann Shortencarier, McCallan Jennifer, Lum Aaron F H, LaBell Rachel, Stieger Susanne M, Matsunaga Terry O, Ferrara Katherine W
Department of Biomedical Engineering, University of California, Davis, Davis, CA 95616, USA.
Ultrasound Med Biol. 2006 Nov;32(11):1771-80. doi: 10.1016/j.ultrasmedbio.2006.03.017.
Drug delivery vehicles that combine ultrasonic and molecular targeting are shown to locally concentrate a drug in a region-of-interest. The drug delivery vehicles, referred to as acoustically active lipospheres (AALs), are microbubbles surrounded by a shell of oil and lipid. In a region limited to the focal area of ultrasound application, circulating AALs are deflected by radiation force to a vessel wall and can subsequently be fragmented. Ligands targeting the alphavbeta3 integrin are conjugated to the AAL shell and increase in vitro binding by 26.5-fold over nontargeted agents. Toxicity assays demonstrate that paclitaxel-containing AALs exert a greater antiproliferative effect after insonation than free paclitaxel at an equivalent concentration. Lastly, ultrasound and molecular targeting are combined to deliver a model drug to the endothelium and interstitium of chorioallantoic membrane vasculature in vivo.
结合超声和分子靶向的药物递送载体可将药物局部集中在感兴趣区域。这种药物递送载体被称为声学活性脂质球（AALs），是由油和脂质外壳包围的微泡。在仅限于超声应用焦点区域的范围内，循环中的AALs会因辐射力而偏向血管壁，随后可能会破碎。靶向αvβ3整合素的配体与AAL外壳结合，与非靶向制剂相比，体外结合增加了26.5倍。毒性试验表明，含紫杉醇的AALs在超声照射后比同等浓度的游离紫杉醇具有更大的抗增殖作用。最后，将超声和分子靶向相结合，在体内将一种模型药物递送至绒毛尿囊膜脉管系统的内皮和间质。
