Bioactive Long-Term Release from Biodegradable Microspheres Preserves Implanted ALG-PLO-ALG Microcapsules from In Vivo Response to Purified Alginate
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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.
KEY WORDSalginate microcapsules biodegradable microspheres diabetes post-grafting response superoxide dismutase and ketoprofen
- 1.Nathan DM. The rationale for glucose control in diabetes mellitus. Endocrinol Metabol Clin North Am. 1992;21:221–35.Google Scholar
- 5.Calafiore R, Basta G. Alginate/poly-L-ornithine microcapsules for pancreatic islet cell immunoprotection. In: Kühtreiber WM, Lanza RP, Chick WL, editors. Cell encapsulation, technology and therapeutics. New York: Birkhäuser; 1999. p. 138–50.Google Scholar
- 6.Calafiore R. Bioartificial pancreas. In: Dumitriu S, editor. Polymeric Biomaterials. New York: Marcel Dekker; 2002. p. 983–1005.Google Scholar
- 11.Vizzardelli C, Molano RD, Pileggi A, Berney T, Cattan P, Fenjves ES, et al. Neonatal porcine pancreatic cell clusters as a potential source for transplantation in humans: Characterization of proliferation, apoptosis, xenoantigen expression and gene delivery with recombinant AAV. Xenotransplantation. 2002;9:14–24.CrossRefPubMedGoogle Scholar
- 13.Living Cell Technologies Updates Progress with Diabetes Clinical Trial. http://www.lctglobal.com/latest-news.php (accessed 10/27/09).
- 14.Open-label Investigation of the Safety and Effectiveness of DIABECELL(R) in Patients With Type I Diabetes Mellitus http://www.clinicaltrials.gov/ct2/show/NCT00940173?term=pig+islets&rank=1 (accessed 10/30/09).
- 20.Luca G, Calafiore R, Basta G, Ricci M, Calvitti M, Neri L, et al. Improved function of rat islets upon co-microencapsulation with Sertoli’s cells in alginate/poly-l-ornithine. AAPSPharmSciTech. 2001;2: article 15.Google Scholar
- 21.Giovagnoli S, Luca G, Casaburi I, Blasi P, Macchiarulo G, Ricci M, et al. Long-term delivery of superoxide dismutase and catalase entrapped in poly(lactide-co-glycolide) microspheres: in vitro effects on isolated neonatal porcine pancreatic cell clusters. J Control Release. 2005;107:395–407.CrossRefPubMedGoogle Scholar
- 37.Giovagnoli S, Blasi P, Ricci M, Rossi C. Biodegradable microspheres as carriers for native superoxide dismutase and catalase delivery. AAPS Pharm Sci Tech. 2004;5(4): article 51Google Scholar
- 39.Shibuya T, Watanade Y, Nalley KA, Fusco A, Salafsky B. The BCA protein determination system: an analysis of several buffers, incubation temperature and protein standards. Tokyo Ika Daigaku Zasshi. 1989;47(4):677–82.Google Scholar
- 41.Basta G, Calafiore R. A process for the ultrapurification of alginates. 2009. WO/2009/093184.Google Scholar
- 44.Active Standard ASTM F2064. Standard guide for characterization and testing of alginates as starting materials intended for use in biomedical and tissue-engineered medical products. 2006. http://www.astm.org/Standards/F2064.htm.
- 46.Blasi P, Schoubben A, Giovagnoli S, Perioli L, Ricci M, Rossi C. Ketoprofen poly(lactide-co-glycolide) physical interaction. AAPSPharmSciTech. 2007;8(2): article 37.Google Scholar