Abstract 11179: Development of a Novel Hybrid Device with Rechargeable Drug-Eluting Capability for Minimally Invasive Treatment of Aortic Aneurysms
Ongoing aortic wall degeneration and subsequent failure of aneurysm exclusion is the major concern after the endovascular aneurysm repair (EVAR). The aortic wall-targeted drug therapy to inhibit the wall degeneration would provide an ideal solution for this concern. Here, we report a novel device, the rechargeable drug delivery system (RDDS), which is capable of charging, recharging and releasing drugs in vivo for the treatment of aortic aneurysms. We have developed basic technologies for RDDS by using neutravidin-biotin interaction. We created the targeted graft, which is a biotinylated polyester graft bound to neutravidin. We also created the target recognition nanocarrier by conjugating drug-containing liposomes and biotinylated bio-nanocapsules (BNCs). We succeeded in incorporating suitable drugs for aneurysm treatment, such as HMG-CoA reductase inhibitors (statins) or a JNK inhibitor, into the BNC-liposome complex. We demonstrated that the target recognition nanocarriers can bind to the target molecule-labeled graft both in vitro experiments and in the blood vessels of live animals. Moreover, we examined the local drug delivery from the graft to the aortic wall in mouse. For this experiment, we placed the graft bound to the statin-containing nanocarriers just close by mouse abdominal aorta, which was stimulated with 0.5M CaCl2. While treatment with calcium caused high expression of MMP-9 in the aortic tissue, the statin-containing graft significantly reduced the MMP-9 expression, indicating the successful local drug delivery from the graft to the aortic wall in vivo. Thus, we propose that RDDS is a possible adjuvant therapy to improve the long-term outcome of EVAR.
- © 2011 by American Heart Association, Inc.