Dextran Sulfate Based Gel Coating for Drug Eluting Balloon Angioplasty

Abstract

Vascular calcification, a consequence of cardiovascular disease, disrupts natural blood flow and can result in death. Common treatment efforts include various anti-inflammatory medications, balloon angioplasty, or stents, with little success in completely reversing calcification. The proposed design focuses on improving current drug-eluting stents by developing a dextran-sulfate-based gel drug delivery system loaded with receptor activator of nuclear kappa B-ligand (RANKL) to induce osteoclast differentiation. To ensure that the gel could properly deliver RANKL, the gel was tested for its affinity for hydroxyapatite (HA), a critical component of calcification, and its ability to withstand shear. Infrared spectroscopy (IR) indicated binding to HA. Preliminary scanning electron microscopy and energy dispersive X-ray spectroscopy (SEM/EDS) results confirmed the presence of calcium on the gel after a one-hour soak in a HA mixture. Shear testing demonstrated that negligible protein, an average of 0.029± 0.024 μg/mL, was sheared off under flow conditions, indicating that the gel is stable for duration of balloon delivery. These preliminary results indicate that a dextran-sulfate-based gel has potential to serve as a therapeutic gel-coating to treat vascular calcification. Future experimentation will include a co-culture study to determine whether osteoclast progenitor cells will properly proliferate and differentiate in the presence of the RANKL-loaded gel. KEYWORDS: Angioplasty; Calcification; Cardiovascular; Dextran; Gel; Osteoclast; Stent; Vascular