PURPOSE: To assess whether prevention of unexpected in vivo adverse inflammatory and immune responses to biohybrid organ grafts for the treatment of Type I Diabetes Mellitus (T1DM) is possible by superoxide dismutase and ketoprofen controlled release. METHODS: Superoxide dismutase and ketoprofen-loaded polyester microspheres were prepared by W/O/W and O/W methods, embodied into purified alginate-poly-L-ornithine-alginate microcapsules and intraperitoneally implanted into CD1 mice. The microspheres were characterized for morphology, size, encapsulation efficiency, enzyme activity and in vitro release. Purified alginate contaminants were assayed, and the obtained microcapsules were investigated for size and morphology before and after implantation over 30 days. Cell pericapsular overgrowth and expression were evaluated by optical microscopy and flow cytometry. RESULTS: Superoxide dismutase and ketoprofen sustained release reduced cell pericapsular overgrowth in comparison to the control. Superoxide dismutase release allowed preserving the microcapsules over 30 days. Ketoprofen-loaded microspheres showed some effect in the immediate post-grafting period. A higher macrophage and T-cell expression was observed for the control group. CONCLUSIONS: Microspheres containing superoxide dismutase and ketoprofen may represent novel tools to limit or prevent unpredictable adverse in vivo response to alginate, thus contributing to improve cell transplantation success rates in T1DM treatment.
PURPOSE: To assess whether prevention of unexpected in vivo adverse inflammatory and immune responses to biohybrid organ grafts for the treatment of Type I Diabetes Mellitus (T1DM) is possible by superoxide dismutase and ketoprofen controlled release. METHODS: Superoxide dismutase and ketoprofen-loaded polyester microspheres were prepared by W/O/W and O/W methods, embodied into purified alginate-poly-L-ornithine-alginate microcapsules and intraperitoneally implanted into CD1mice. The microspheres were characterized for morphology, size, encapsulation efficiency, enzyme activity and in vitro release. Purified alginate contaminants were assayed, and the obtained microcapsules were investigated for size and morphology before and after implantation over 30 days. Cell pericapsular overgrowth and expression were evaluated by optical microscopy and flow cytometry. RESULTS: Superoxide dismutase and ketoprofen sustained release reduced cell pericapsular overgrowth in comparison to the control. Superoxide dismutase release allowed preserving the microcapsules over 30 days. Ketoprofen-loaded microspheres showed some effect in the immediate post-grafting period. A higher macrophage and T-cell expression was observed for the control group. CONCLUSIONS: Microspheres containing superoxide dismutase and ketoprofen may represent novel tools to limit or prevent unpredictable adverse in vivo response to alginate, thus contributing to improve cell transplantation success rates in T1DM treatment.
Authors: Riccardo Calafiore; Giuseppe Basta; Giovanni Luca; Angelo Lemmi; M Pia Montanucci; Giuseppe Calabrese; Leda Racanicchi; Francesca Mancuso; Paolo Brunetti Journal: Diabetes Care Date: 2006-01 Impact factor: 19.112
Authors: A M James Shapiro; Camillo Ricordi; Bernhard J Hering; Hugh Auchincloss; Robert Lindblad; R Paul Robertson; Antonio Secchi; Mathias D Brendel; Thierry Berney; Daniel C Brennan; Enrico Cagliero; Rodolfo Alejandro; Edmond A Ryan; Barbara DiMercurio; Philippe Morel; Kenneth S Polonsky; Jo-Anna Reems; Reinhard G Bretzel; Federico Bertuzzi; Tatiana Froud; Raja Kandaswamy; David E R Sutherland; George Eisenbarth; Miriam Segal; Jutta Preiksaitis; Gregory S Korbutt; Franca B Barton; Lisa Viviano; Vicki Seyfert-Margolis; Jeffrey Bluestone; Jonathan R T Lakey Journal: N Engl J Med Date: 2006-09-28 Impact factor: 91.245
Authors: Stefano Giovagnoli; Giovanni Luca; Ivan Casaburi; Paolo Blasi; Giacomo Macchiarulo; Maurizio Ricci; Mario Calvitti; Giuseppe Basta; Riccardo Calafiore; Carlo Rossi Journal: J Control Release Date: 2005-09-20 Impact factor: 9.776