Following vascular bypass interventions, autologous saphenous vein grafts are prone to fail due to intimal hyperplasia development. An atorvastatin (ATV)-eluting tubular mesh coated with poly(d,l-lactide-co-glycolisde) acid (PLGA) was designed for perivascular application, in order to prevent the development of this pathology. Formulation parameters such as PLGA molecular weight, concentration of ATV and PLGA in the coating solution and number of coatings were investigated to optimise the mesh in terms of drug loading efficacy, drug release kinetics and mechanical properties. Using the dip-coating technique, 1.6 mg of ATV was loaded on a tubular 5 cm long mesh. The most important parameter influencing ATV loading was the concentration of the drug in the coating solution. In vitro an ATV release profile combining an initial fast release over 3 days and a sustained release over 40 days was obtained; consistent with the timeframe of hyperplasia development. The amount of PLGA polymer coating as well as the molecular weight of the polymer were optimized to achieve these kinetics. A poly(d,l-lactide-co-caprolactone) (PLCL) layer was sprayed on the external side of the PLGA coated tubular mesh to restrict the ATV release to the vascular tissue. Scanning electron microscopy observation showed that the macroporosity of the mesh was preserved after coating, while texture analysis demonstrated that its elasticity decreased slightly.
Keywords: Atorvastatin; Coating; Mesh; PLCL → Poly(d,l-lactide-co-caprolactone); PLGA → Poly(d,l-lactide-co-glycolide); Perivascular; Polyethylene terephthalate.
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