Research Paper

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 GiovagnoliAffiliated withDipartimento di Chimica e Tecnologia del Farmaco, Faculty of Pharmacy, University of Perugia Email author 
  • , Paolo BlasiAffiliated withDipartimento di Chimica e Tecnologia del Farmaco, Faculty of Pharmacy, University of Perugia
  • , Giovanni LucaAffiliated withDipartimento di Medicina Interna (Di.M.I.), Sezione di Medicina Interna e Scienze Metaboliche ed Endocrine, School of Medicine, University of Perugia
  • , Francesca FallarinoAffiliated withDipartimento di Medicina Sperimentale e Scienze Biochimiche, University of Perugia
  • , Mario CalvittiAffiliated withDipartimento di Medicina Sperimentale e Scienze Biochimiche, University of Perugia
  • , Francesca MancusoAffiliated withDipartimento di Medicina Sperimentale e Scienze Biochimiche, University of Perugia
  • , Maurizio RicciAffiliated withDipartimento di Chimica e Tecnologia del Farmaco, Faculty of Pharmacy, University of Perugia
  • , Giuseppe BastaAffiliated withDipartimento di Medicina Interna (Di.M.I.), Sezione di Medicina Interna e Scienze Metaboliche ed Endocrine, School of Medicine, University of Perugia
  • , Ennio BecchettiAffiliated withDipartimento di Medicina Sperimentale e Scienze Biochimiche, University of Perugia
    • , Carlo RossiAffiliated withDipartimento di Chimica e Tecnologia del Farmaco, Faculty of Pharmacy, University of Perugia
    • , Riccardo CalafioreAffiliated withDipartimento di Medicina Interna (Di.M.I.), Sezione di Medicina Interna e Scienze Metaboliche ed Endocrine, School of Medicine, University of Perugia

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Abstract

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.

KEY WORDS

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