Development of a nanoporous and multilayer drug-delivery platform for medical implants

Abstract

Varvara Karagkiozaki,1 Eleftherios Vavoulidis,1 Panagiotis G Karagiannidis,1 Maria Gioti,1 Dimitrios G Fatouros,2 Ioannis S Vizirianakis,3 Stergios Logothetidis11Lab for Thin Films–Nanosystems and Nanometrology, Physics Department, 2Department of Pharmaceutical Technology, 3Laboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, GreeceAbstract: Biodegradable polymers can be applied to a variety of implants for controlled and local drug delivery. The aim of this study is to develop a biodegradable and nanoporous polymeric platform for a wide spectrum of drug-eluting implants with special focus on stent-coating applications. It was synthesized by poly(DL-lactide-co-glycolide) (PLGA 65:35, PLGA 75:25) and polycaprolactone (PCL) in a multilayer configuration by means of a spin-coating technique. The antiplatelet drug dipyridamole was loaded into the surface nanopores of the platform. Surface characterization was made by atomic force microscopy (AFM) and spectroscopic ellipsometry (SE). Platelet adhesion and drug-release kinetic studies were then carried out. The study revealed that the multilayer films are highly nanoporous, whereas the single layers of PLGA are atomically smooth and spherulites are formed in PCL. Their nanoporosity (pore diameter, depth, density, surface roughness) can be tailored by tuning the growth parameters (eg, spinning speed, polymer concentration), essential for drug-delivery performance. The origin of pore formation may be attributed to the phase separation of polymer blends via the spinodal decomposition mechanism. SE studies revealed the structural characteristics, film thickness, and optical properties even of the single layers in the triple-layer construct, providing substantial information for drug loading and complement AFM findings. Platelet adhesion studies showed that the dipyridamole-loaded coatings inhibit platelet aggregation that is a prerequisite for clotting. Finally, the films exhibited sustained release profiles of dipyridamole over 70 days. These results indicate that the current multilayer phase therapeutic approach constitutes an effective drug-delivery platform for drug-eluting implants and especially for cardiovascular stent applications.Keywords: drug delivery, implants, stents, polymers, spin-coating, atomic force microscopy