Preparation and in vitro and in vivo characterization of composite microcapsules for cell encapsulation

Cell encapsulation technology raises great hopes in medicine and biotechnology. Transplantation of encapsulated pancreatic islets represents a promising approach to the final cure of type 1 diabetes mellitus. Unfortunately, long-term graft survival and functional competence remain only partially fulfilled. Failure was often ascribed to the lack of biocompatibility generating inflammatory response, limited immunobarrier competence, hypoxia, and low beta-cell replication. In the present work, ketoprofen loaded biodegradable microspheres, embedded into alginate/poly-L-ornithine/alginate microcapsules, were prepared in order to release ketoprofen at early stages after implantation. Morphology, size, in vitro release behaviour, and in vivo biocompatibility were assessed. The effect of some preparation parameters was also evaluated. Polymeric microspheres were spherical and smooth, two populations of about 5 and 20 mu m of mean diameter characterized the particle size distribution. A high burst effect was observed for all preparations during in vitro release studies. Ketoprofen, plasticizing the polymeric matrix, could be responsible of this release behaviour. Alginate/poly-L-ornithine/alginate microcapsules were not modified upon ketoprofen loaded microspheres encapsulation and an optimal dispersion was obtained. Composite system showed good biocompatibility when a high molecular weight polymer was employed. Therefore a potentially suitable composite system for cell encapsulation was obtained. This system may be successfully used to release NSAIDs and other active molecules capable to improve cell system functional performance and life-span. (c) 2006 Elsevier B.V. All rights reserved.