Abstract No. 433 Dipyridamole-loaded electrospun polymer scaffold based on polyethylene glycol/polycaprolactone for localized drug delivery

Abstract

One of the major causes of failure of vascular interventions is neointimal hyperplasia (NIH). To prevent the development of NIH, drugs must be delivered locally, for which drug-eluting, resorbable polymer scaffolds present a promising strategy (Liechty et.al., 2010). In this study, dipyridamole (DPA)-eluting scaffolds based on polyethylene glycol (PEG) and polycaprolactone (PCL) were fabricated and tested. PCL (MW 80,000) and PEG (MW 8000) were blended in chloroform at 3:1, 1:1, and 1:3 mass ratios for a final polymer concentration of 200 mg/mL. DPA was added at 0.1 mg/mL. Electrospinning was done with Avecta’s Spraybase system at 1 mL volume, 1 mL/hr flow rate, 15.0 kV voltage, and 15 cm distance. Bilayer scaffolds were fabricated with a layer containing DPA on a layer without DPA. Scaffolds were characterized by scanning electron microscopy (SEM) and porosity and tested for DPA release, cell proliferation, and blood biocompatibility. SEM images of the electrospun scaffolds revealed that adding PEG to PCL decreased the fiber diameter and pore size of the scaffolds. Scaffolds fabricated from 3:1 PCL:PEG demonstrated the slowest cumulative rate of release, with 9.17% cumulative release after 8 days. Scaffold fabricated from 3:1 PCL:PEG also exhibited higher levels of cell attachment and proliferation. With the 3:1 bilayer, RF24 endothelial cells proliferated on non-eluting side (luminal), while MOVAS smooth muscle cells were inhibited on DPA-eluting side (adventitial). No scaffolds showed significant hemolysis and clotting upon contact with blood. Significant differences were observed when compared to positive control (multiple t-tests, P < 0.001). PCL and PEG blended scaffolds in a 3:1 PCL:PEG mass ratio demonstrate slow and sustained drug release, adjustable cell proliferation properties, and biocompatibility, making for potential graft candidates. This approach may also be used for local and controlled release of other drugs, such as chemotherapeutic agents.