Patients with limited preoperative ambulatory ability, age > or = 70, dementia, end-stage renal disease, and advanced coronary artery disease perform poorly and should probably be grouped with bedridden patients, who traditionally have been best served with a palliative above knee amputation. Conversely, younger healthy patients with below knee amputations achieved functional outcomes similar to what might be expected after successful lower extremity revascularization. Amputation in these instances should probably not be considered a failure of therapy but another treatment option capable of extending functionality and independent living.

Prosthetic AV access in the thigh is associated with higher morbidity compared with that reported for the upper extremity, and should be considered only if no upper extremity AV access option is available. Early access failure and the requirement for an increased number of interventions to reestablish and maintain access patency are more common in patients with diabetes mellitus and obesity. The number of interventions per year of access patency is a valuable end point when assessing the outcome of AV access procedures.

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Rationale Matrix metalloproteinases (MMPs)-mediated extracellular matrix destruction is the major cause of development and progression of abdominal aortic aneurysms (AAA). Systemic treatments of MMP inhibitors have shown effectiveness in animal models but it did not translate to clinical success either due low doses used or systemic side-effects of MMP inhibitors. We propose a targeted nanoparticle based delivery of MMP inhibitor at very low doses to the AAA site. Such therapy will be an attractive option for preventing expansion of aneurysms in patients without systemic side effects. Objective Our previous study showed that poly D, L-lactide (PLA) nanoparticles (NPs) conjugated with an anti-elastin antibody could be targeted to the site of an aneurysm in a rat model of AAA. In the study reported here, we tested whether such targeted NPs could deliver the MMP inhibitor batimastat (BB-94) to the site of an aneurysm and prevent aneurysmal growth. Methods and Results PLA NPs were loaded with BB-94 and conjugated with an elastin antibody. Intravenous injections of elastin antibody-conjugated BB-94-loaded NPs (EL-NP-BB94) targeted the site of aneurysms and delivered BB-94 in a calcium chloride injury-induced AAA in rats. Such targeted delivery inhibited MMP activity, elastin degradation, calcification, and aneurysmal development in the aorta (269% expansion in control vs. 40% EL-NP-BB94) at a low dose of BB-94. The systemic administration of BB-94 alone at the same dose was ineffective in producing MMP inhibition. Conclusions Targeted delivery of MMP inhibitors using NPs may be an attractive strategy to inhibit aneurysmal progression.