Targeted semi-polymerized shell microbubbles for detection of early post-surgical abdominal adhesions
Gormley, Catherine Anne
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Post-surgical abdominal adhesions, initially a fibrinous matrix linking two organs or tissues which matures to scar tissue, form after nearly 90% of abdominal or pelvic surgeries. Adhesions cause a number of serious post-operative complications, including small bowel obstructions, female infertility, chronic pain, and reoperation complications. Adhesions typically are not diagnosed until long after formation when the patient presents complication-related symptoms. Both the diagnosis and treatment require another invasive surgery and these procedures lead to further adhesion formation. This inability to non-invasively assess adhesion formation means that most promising anti-adhesion agents do not advance to human trials. To address this problem, we have developed a polymerized-shell microbubble (PSM) as an ultrasound (US) contrast agent to target fibrin, an early marker of adhesion formation that is not present in the healthy peritoneum. We have characterized the in vitro stability and fibrin binding properties of these PSMs. For adhesion applications, microbubbles require long term stability on the order of days. We can modify the degree of shell polymerization of the PSMs to achieve stability up to 1 week. Achieving long-term stability through shell modification impacts the acoustic properties of the microbubbles, therefore, there is a trade-off between bubble stability and echogenicity. Furthermore, the fibrin-binding dynamics of our targeted peptide are not well understood, and we have performed systematic studies on this property. Our results show these fibrin-targeted PSMs can be successfully fabricated with two methods of production. We have shown the long-term stability of these PSMs and that they bind selectively to fibrin. All together, these studies indicate that fibrin-targeted PSMs can both aid in the early diagnosis of surgical adhesions and help overcome this major roadblock preventing clinical trials.