The Need

Imaging and re-intervention procedures, necessary to maintain open blood vessels following vascular reconstruction surgery, are expensive. For example, the cost of maintenance for an arteriovenous (AV) fistula used in hemodialysis access has been estimated at $15,000/year. In bypass and AV fistula surgeries, veins are abruptly exposed to high pressures and flow rates of the arterial system and increased turbulence. In response, the vein undergoes intimal hyperplasia (IH), which can lead to stenosis and failure with failure rates for such grafts approaching 50%. Bypass, trauma reconstruction, and AV fistula surgeries are all categorized as open vascular reconstruction surgeries and are attractive targets for anti-stenosis technology. There are no FDA approved clinical options for preventing IH driven stenosis after open vascular reconstruction surgeries.

Over 400,000 open vascular reconstructions are performed in the US each year for heart and peripheral bypasses. As of 2018, 550,000 Americans received dialysis every year for end stage renal disease. AV fistula surgery is preferred for long-term hemodialysis vascular access. Thus, the need for improved anti-stenosis technology is substantial.

The Technology

OSU inventors have developed a novel anti-stenosis technology. Their product candidate (Pericelle, all-inclusive kit) combines a uni-molecular micelle nanoparticle and a hydrogel, which together facilitate localized and sustained delivery of the anti-stenotic drug, rapamycin. Rapamycin is an approved drug of demonstrated efficacy as an anti-stenotic agent in endovascular procedures, where the delivery mechanism is rapamycin-eluting stents. Such stents are not usable in open vascular reconstruction surgeries.

In brief, immediately following vessel anastomosis, rapamycin loaded nanoparticles suspended in a thermo-sensitive hydrogel are applied to the outside of the reconstructed vessel. Upon contact with the vessel, the gel warms and solidifies, thereby restricting nanoparticles and drug to the targeted vessel. Nanoparticles provide sustained local release of rapamycin for over three months, allowing prolonged effective dose delivery to the vulnerable vessel with minimal systemic exposure. The particles specifically target pathogenic smooth muscle cells to shield normal cells from toxicity. When loaded with anti-restenotic drugs, they inhibit initial hyperplasia, the major cause of restenosis.

A prototype of the delivery system was tested within a rat model and showed after 3 months initial hyperplasia was still 80% inhibited compared to the control.

Commercial Applications

• Enables vascular surgeons to prevent stenosis following open vascular reconstruction surgeries

Benefits/Advantages

• Prolonged, effective dose delivery
• Nanoparticles and anti-stenotic drug restricted to targeted vessel; minimal systemic exposure

Publications

Chen, G., et al. Unimolecular Micelle-Based Hybrid System for Perivascular Drug Delivery Produces Long-Term Efficacy for Neointima Attenuation in Rats. Biomacromolecules. 2017, 18, 2205–2213.

Patents

Issued application in the U.S.A.