Pharmaceutical Research

, Volume 27, Issue 2, pp 285–295

Bioactive Long-Term Release from Biodegradable Microspheres Preserves Implanted ALG-PLO-ALG Microcapsules from In Vivo Response to Purified Alginate

  • Stefano Giovagnoli
  • Paolo Blasi
  • Giovanni Luca
  • Francesca Fallarino
  • Mario Calvitti
  • Francesca Mancuso
  • Maurizio Ricci
  • Giuseppe Basta
  • Ennio Becchetti
  • Carlo Rossi
  • Riccardo Calafiore
Research Paper



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.


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.


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.


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.


alginate microcapsules biodegradable microspheres diabetes post-grafting response superoxide dismutase and ketoprofen 


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Stefano Giovagnoli
    • 1
  • Paolo Blasi
    • 1
  • Giovanni Luca
    • 2
  • Francesca Fallarino
    • 3
  • Mario Calvitti
    • 3
  • Francesca Mancuso
    • 3
  • Maurizio Ricci
    • 1
  • Giuseppe Basta
    • 2
  • Ennio Becchetti
    • 3
  • Carlo Rossi
    • 1
  • Riccardo Calafiore
    • 2
  1. 1.Dipartimento di Chimica e Tecnologia del Farmaco, Faculty of PharmacyUniversity of PerugiaPerugiaItaly
  2. 2.Dipartimento di Medicina Interna (Di.M.I.), Sezione di Medicina Interna e Scienze Metaboliche ed Endocrine, School of MedicineUniversity of PerugiaPerugiaItaly
  3. 3.Dipartimento di Medicina Sperimentale e Scienze BiochimicheUniversity of PerugiaPerugiaItaly

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