Antithrombotic Peptide Delivery from Glow-Discharge Plasma-Coated Controlled Release Matrices

Abstract

A novel polymeric matrix system has been developed to deliver agents to block platelet adhesion or inhibit thrombin activation on implanted biomaterials. The base material of the system used was BioSpan®, a medical-grade polyether-urethane urea (PEUU) elastomer, which contained a dispersion of an active agent: either an anti-platelet-adhesion peptide (echistatin), small peptide (RGDSGY), or direct antithrombin peptide (hirudin), along with bovine serum albumin (BSA) or poly(ethylene glycol) (PEG) as an excipient and poreformer. The PEUU-peptide matrix was subsequently processed using radio-frequency glowdischarge (RFGD) plasma polymerization of acrylate monomers, either 2-hydroxyethyl methacrylate (HEMA), n-butyl methacrylate (BMA), or N-isopropyl acrylamide (NIPAAm) to create a barrier membrane. Control of plasma parameters changed the cross linking of this thin, conformal barrier, and produced different release rates of the active agents from the matrix. Biologically active echistatin and hirudin were delivered successfully, but some matrices exhibited a limited reduction in release rate due to osmotic rupturing of the matrix and coating. For RGDSGY-containing matrices, the reduction in release rate with RFGD plasma coating was greatest for matrices with PEG excipients of 10,000 and 20,000 molecular weight.