title: Ketoprofen controlled release from composite microcapsules for cell encapsulation: effect on post-transplant acute inflammation.
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 inflammatory response, or limited immunobarrier competence or hypoxia or finally, low beta-cell replication. In order to prevent severe inflammation at early stages after implantation, composite microcapsules were designed. Biodegradable microspheres containing 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.
authors.affiliation: Department of Chemistry and Technology of Drugs, School of Pharmacy, University of Perugia, Via del Liceo 1, 06123 Perugia, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Ricci
authors.forename: Paolo
authors.initials: P
authors.lastname: Blasi
authors.forename: Stefano
authors.initials: S
authors.lastname: Giovagnoli
authors.forename: Carlo
authors.initials: C
authors.lastname: Rossi
authors.forename: Giacomo
authors.initials: G
authors.lastname: Macchiarulo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Luca
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basta
authors.forename: Riccardo
authors.initials: R
authors.lastname: Calafiore
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000627:therapeutic use*; D002214:Capsules; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations; D004055:Differential Thermal Analysis; D004339:Drug Compounding; D005079:Excipients; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects; D007660:Ketoprofen / Q000008:administration & dosage* / Q000627:therapeutic use*; D019344:Lactic Acid; D008297:Male; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D016377:Organ Transplantation / Q000009:adverse effects*; D010316:Particle Size; D011091:Polyesters; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D003692:Delayed-Action Preparations; D005079:Excipients; D011091:Polyesters; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D007660:Ketoprofen