Abstract
Ongoing aortic wall degeneration and subsequent aneurysm exclusion failure are major concerns after an endovascular aneurysm repair with a stent-graft. An ideal solution would be a drug therapy that targets the aortic wall and inhibits wall degeneration. Here, we described a novel drug delivery system, which allowed repetitively charging a graft with therapeutic drugs and releasing them to the aortic wall in vivo. The system was composed of a targeted graft, which was labeled with a small target molecule, and the target-recognizing nanocarrier, which contained suitable drugs. We developed the targeted graft by decorating a biotinylated polyester graft with neutravidin. We created the target-recognizing nanocarrier by conjugating drug-containing liposomes with biotinylated bio-nanocapsules. We successfully demonstrated that the target-recognizing nanocarriers could bind to the targeted graft, both in vitro and in blood vessels of live mice. Moreover, the drug released from our drug delivery system reduced the expression of matrix metalloproteinase-9 in mouse aortas. Thus, this hybrid system represents a first step toward an adjuvant therapy that might improve the long-term outcome of endovascular aneurysm repair.
Highlights
Abdominal aortic aneurysm (AAA) is a noteworthy disease that causes segmental expansion and aortic rupture [1,2]
The grafts biotinylated with amine-coupling contained 3.1 nmol/cm2 biotin, and the grafts biotinylated with a pHEMA coating contained 245 nmol/cm2 biotin
The pHEMA-coating technique greatly increased the amount of biotin on the graft (Figure 2C)
Summary
Abdominal aortic aneurysm (AAA) is a noteworthy disease that causes segmental expansion and aortic rupture [1,2]. MMP-9 is the primary enzyme responsible for aortic wall degradation. We previously reported that pharmacologic treatment with hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) inhibited the secretion of MMP-9, a marker of vessel wall degeneration, from human aneurysm tissues in culture [6]. We showed in a mouse model that pharmacologic inhibition of c-Jun N-terminal kinase (JNK), a proinflammatory signaling molecule, could successfully treat aortic aneurysms [11,12].
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