Kim D D, Takeno M M, Ratner B D, Horbett T A
Department of Bioengineering, University of Washington, Seattle 98195, USA.
Pharm Res. 1998 May;15(5):783-6. doi: 10.1023/a:1011987423502.
Biomaterials which release locally high concentrations of antithrombotic agents should lessen the thrombogenicity of the materials. To evaluate this approach, we prepared novel polyurethane matrices loaded with hirudin and coated them with 2-hydroxyethyl methacrylate (HEMA) by glow discharge plasma deposition (GDPD) to reduce the release rate.
Polyurethane (BioSpan) matrices containing hirudin and pore former (d-mannitol or BSA) were prepared by the solvent casting method. HEMA plasma deposition was then applied using GDPD technique to create a diffusional barrier film on the surface of the matrices. The effect of pore former and HEMA plasma coating on the release of hirudin was systematically investigated. Surface properties of matrices was also studied using Scanning Electron Microscopy (SEM) and Electron Spectroscopy for Chemical Analysis (ESCA).
The release of hirudin from BioSpan matrix could be controlled by changing the weight fraction and particle size of pore former. HEMA plasma treatment of matrices produced a thin, highly cross-linked film on the surface. The initial burst and subsequent release of hirudin was significantly reduced after HEMA plasma coating, which suggested that the plasma disposition acted as a diffusional barrier and limited the release of hirudin incorporated in the polyurethane matrix.
The plasma coating served as a diffusional barrier, and could work to control the release kinetics of hirudin by changing the various plasma coating conditions. Local delivery of hirudin using these biomaterials at the site of cardiovascular diseases can have the advantage of regional high levels of hirudin, as well as lowering systemic hirudin exposure, thereby minimizing the possibility of side effects.
