Ketoprofen release from composite microcapsules for cell encapsulation: effect on acute inflammation.

Purpose. To prepare, characterize and in vivo evaluate a composite microcapsule obtained enveloping ketoprofen loaded microspheres (MS) within alginate/poly-L-ornithine microcapsules for cell encapsulation in order to prevent/treat the acute inflammation in the immediate posttransplant period. Methods. Poly-lactide (PLA) and Poly-lactide-co-glicolide (PLGA) MS were prepared by solvent evaporation method. MS morphology and size were investigated by scanning electron microscopy and “single particle optical sensing” technique, respectively. In vitro release studies were carried out in 0.1M phosphate buffer, pH 7.4 at 37°C. Interaction was investigated by Differential Scanning Calorimetry (DSC). Alginate/poly-L-ornithine microcapsules were prepared by extrusion method and characterized by optical microscopy analysis. Microcapsules biocompatibility and efficacy were investigated in CD-1 mice and Sprague/Dawley rats respectively. Results. Loaded and blank MS had similar size distribution with a mean diameter of 5 μm. The MS were spherical and smooth, with a non porous surface. Conventional and composite microcapsules were prepared using an atomizing method resulting in fabrication of monodisperse spherical beads with 600±50 μm average diameter. A high burst effect characterized the release profiles of all the assayed preparations, probably due to the plasticizing effect on the polymer of both ketoprofen and water. DSC data showed a microsphere Tg below 37°C. Biocompatibility studies showed no inflammation for PLA composite microcapsules after two months of intraperitoneal implantation in rodents. Efficacy studies showed that, after six days of implantation, the treated group was practically free of inflammation, while controls presented strong pericapsules overgrowth. Conclusion. It was preliminary observed that acute inflammatory response against microcapsules for cell encapsulation could be controlled using a composite system releasing ketoprofen. This approach may be used also to release other active molecules potentially useful to provide the implanted system with better performance.