Bioactive long-term release from biodegradable microspheres preserves implanted ALG-PLO-ALG microcapsules from in vivo response to purified alginate.
OBJECTIVE
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.
Giovagnoli
Stefano
S
Dipartimento di Chimica e Tecnologia del Farmaco, Faculty of Pharmacy, University of Perugia, Via del Liceo 1, Perugia, 06123, Italy. eureka@unipg.it
Blasi
Paolo
P
Luca
Giovanni
G
Fallarino
Francesca
F
Calvitti
Mario
M
Mancuso
Francesca
F
Ricci
Maurizio
M
Basta
Giuseppe
G
Becchetti
Ennio
E
Rossi
Carlo
C
Calafiore
Riccardo
R
D020341:Absorbable Implants; D000464:Alginates / Q000008:administration & dosage* / Q000302:isolation & purification / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D002214:Capsules; D003692:Delayed-Action Preparations; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism; D020723:Glucuronic Acid / Q000008:administration & dosage / Q000302:isolation & purification / Q000493:pharmacokinetics; D006603:Hexuronic Acids / Q000008:administration & dosage / Q000302:isolation & purification / Q000493:pharmacokinetics; D051379:Mice; D008863:Microspheres; D010316:Particle Size; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*
D000464:Alginates; D002214:Capsules; D003692:Delayed-Action Preparations; D006603:Hexuronic Acids; D010455:Peptides; C008973:polyornithine; D020723:Glucuronic Acid