Abdominal aortic aneurysm (AAA), occurs when there is an enlarged portion of the abdominal aorta, and accounts for approximately 10,000 deaths per year in the United States. Current treatments include surgical intervention or minimally invasive laparoscopic repair. However, the AAA can rupture, and the patient will not survive surgery or sometimes even reach the hospital. There are no viable pharmacological based treatments for AAA patients, even to reduce the enlargement. This results in the enlargement having to be continuously monitored, which causes constant anxiety for the patient that it could rupture at any moment. Of the drug candidates that have been tested, there have been toxicity concerns and a narrow therapeutic window. This highlights the need for effective pharmacological based treatments for AAA patients.
Researchers in the Department of Surgery have developed a targeted nanoparticle drug delivery system that uses peptide amphiphiles (PA). These PA spontaneously self-assemble into nanofibers when placed in an aqueous environment and are customizable to target a tissue of interest for delivery of a therapeutic agent. A targeting sequence is attached to a PA backbone and through co-assembly with other non-targeted PAs, the PAs can encapsulate drugs in their hydrophobic core. This allows for delivery of drugs that would otherwise display poor oral bioavailability and allow for delivery directly to a tissue of interest, such as an abdominal aortic aneurysm to reduce the enlargement. Synthesis, purification, characterization, and specific targeting by nanofibers to an abdominal aortic aneurysm has been demonstrated in an animal model. The nanofibers present a drug delivery system that is biodegradable, biocompatible, easily delivered by intravenous administration, customizable, and targeted for improved treatment of patients suffering from abdominal aortic aneurysms.
• Targeted drug delivery approach, which provides maximal therapeutic effect to the aneurysmal tissue without systemic adverse effects.
• Encapsulation of hydrophobic drugs improve therapeutic bioavailability.
• Customized targeting to a tissue of interest allows for wide applicability of the system to other diseases.
In addition to treating patients suffering from abdominal aortic aneurysms, the targeted nanofibers can be used for treating patients with aneurysms present in the thoracic aorta or the peripheral arteries.