Ultrasound-microbubble targeted delivery of ICAM-1 in mouse model of peripheral arterial disease

Background/introduction Peripheral arterial disease (PAD) affects 12 million people in the United States. Unfortunately, current treatments are highly invasive and have limited efficacy. Ultrasound (US) in conjunction with microbubbles (MB) has recently been explored as a non-invasive strategy for the delivery of intravascularly circulating therapeutic agents. US mediated MB oscillation can lead to non-damaging, reversible and localized vascular permeabilization resulting in substantial increases of nanoparticle (NP) concentrations in US-treated tissue. Furthermore, by coating NPs with a brush layer of polyethylene glycol (PEG), NPs have long circulating half-lives and limited toxicity. This study investigates the ability of US to deliver ICAM-1-bearing PEG/polyethylenimine (PEG/PEI) NPs to the vascular endothelium in a mouse model of PAD. ICAM-1, an adhesion molecule, expressed postocclusion by the endothelium of collateral arteries has previously been shown to aid in blood flow restoration. Overexpression of ICAM-1 in this model aims to reestablish pre-occlusion blood flow non-invasively.