Department of Biomedical Engineering, University of California, Davis, CA 95616, USA.
J Control Release. 2010 Apr 2;143(1):13-22. doi: 10.1016/j.jconrel.2009.12.010. Epub 2009 Dec 16.
The design of delivery vehicles that are stable in circulation but can be activated by exogenous energy sources is challenging. Our goals are to validate new imaging methods for the assessment of particle stability, to engineer stable and activatable particles and to assess accumulation of a hydrophilic model drug in an orthotopic tumor. Here, liposomes were injected into the tail vein of FVB mice containing bilateral Met-1 tumors and imaged in vivo using microPET and optical imaging techniques. Cryo-electron microscopy was applied to assess particle shape prior to injection, ex vivo fluorescence images of dissected tissues were acquired, excised tissue was further processed with a cell-digest preparation and assayed for fluorescence. We find that for a stable particle, in vivo tumor images of a hydrophilic model drug were highly correlated with PET images of the particle shell and ex vivo fluorescence images of processed tissue, R(2)=0.95 and R(2)=0.99 respectively. We demonstrate that the accumulation of a hydrophilic model drug is increased by up to 177 fold by liposomal encapsulation, as compared to accumulation of the drug at 24 hours.
设计在循环中稳定但可以被外源性能量源激活的递药载体具有挑战性。我们的目标是验证用于评估颗粒稳定性的新成像方法，设计稳定且可激活的颗粒，并评估亲水性模型药物在原位肿瘤中的积累。在这里，将脂质体注入含有双侧 Met-1 肿瘤的 FVB 小鼠的尾静脉中，并使用 microPET 和光学成像技术进行体内成像。应用冷冻电子显微镜在注射前评估颗粒形状，获取离体组织的荧光图像，进一步用细胞消化液处理切除的组织并进行荧光检测。我们发现，对于稳定的颗粒，亲水性模型药物的体内肿瘤图像与颗粒壳的 PET 图像高度相关，与处理组织的离体荧光图像的相关性分别为 R(2)=0.95 和 R(2)=0.99。我们证明，与 24 小时时药物的积累相比，脂质体包封可使亲水性模型药物的积累增加多达 177 倍。
