Ketoprofen controlled release from composite microcapsules for cell encapsulation: Effect on post-transplant acute inflammation Maurizio Ricci a , Paolo Blasi a , Stefano Giovagnoli a , Carlo Rossi a, * , Giacomo Macchiarulo b , Giovanni Luca b , Giuseppe Basta b , Riccardo Calafiore b a Department of Chemistry and Technology of Drugs, School of Pharmacy, University of Perugia, Via del Liceo 1, 06123 Perugia, Italy b Department of Internal Medicine, School of Medicine, University of Perugia, Via E. Dal Pozzo, 06126 Perugia, Italy Received 13 April 2005; accepted 21 June 2005 Available online 29 August 2005 Abstract Cell encapsulation technology raises hopes in medicine and biotechnology. Encapsulated pancreatic islets is a promising approach for the final solution of Type 1 diabetes. Unfortunately, evidence of long-term encapsulated islet graft survival and functional competence lies behind expectancy. Failure was often ascribed to the lack of biocompatibility generating inflam- matory response, or limited immunobarrier competence or hypoxia or finally, low h-cell replication. In order to prevent severe inflammation at early stages after implantation, composite microcapsules were designed. Biodegradable microspheres contain- ing ketoprofen were enveloped into the well established alginate/poly-l-ornithine/alginate capsules. Polyester microspheres were prepared, by solvent evaporation, and characterized for encapsulation efficiency, particle size and in vitro release. Biocompatibility and efficacy to prevent the inflammatory response were studied in vivo. Good encapsulation efficiency and the desired particle size were achieved. In vitro release studies evidenced a high burst effect probably due to a plasticizing effect of both water and ketoprofen. The composite systems showed good biocompatibility and capacity to completely avoid the inflammatory response and the pericapsular cell overgrowth. In conclusion, the inflammatory response in the immediate post- transplant period can be circumvented using multicompartment microcapsules releasing non-steroidal anti inflammatory drugs. D 2005 Published by Elsevier B.V. Keywords: Cell encapsulation; Alginate; Inflammation; Ketoprofen; Polyesters 1. Introduction Cell encapsulation technology raises hopes in med- icine and biotechnology [1]. In fact, transplantation of encapsulated cells has been proposed for therapy of a widely range of diseases such as diabetes [2], hemo- philia [3], cancer [4] and renal failure [5]. Since 0168-3659/$ - see front matter D 2005 Published by Elsevier B.V. doi:10.1016/j.jconrel.2005.06.023 * Corresponding author. Tel.: +39 075 5855127; fax: +39 075 5855163. E-mail address: cfrossi@unipg.it (C. Rossi). Journal of Controlled Release 107 (2005) 395 – 407 www.elsevier.com/locate/jconrel