Biomaterials 24 (2003) 3101–3114 . Multifunctional microcapsules for pancreatic islet cell entrapment: design, preparation and in vitro characterization Giovanni Luca a,c , Giuseppe Basta b , Riccardo Calafiore b , Carlo Rossi a , Stefano Giovagnoli a , Elisabetta Esposito d , Claudio Nastruzzi a, * a Department of Medicinal Chemistry and Pharmaceutics, University of Perugia, Perugia, Italy b Department of Internal Medicine, Section of Internal Medicine and Endocrine and Metabolic Sciences, School of Medicine, University of Perugia, Perugia, Italy c Consorzio Interuniversitario per i Trapianti d’organo, Rome, Italy d Department of Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy Received 26 September 2002; accepted 20 February 2003 Abstract Great advances in cell transplantation have been made, including the recent, remarkable success in pancreatic islet transplantation for the treatment of type 1 diabetes mellitus. Unfortunately, the transplanted cells are very susceptible to oxidative stress that cause severe damage to either allo- or xenogeneic islets upon graft in diabetic patients. Consequently, the transplanted islet functional life span is significantly shortened. The aim of this study was to examine the possible effects of antioxidants on in vitro cultured adult rat islets, and to evaluate the effects of a prolonged-release formulation, in form of cellulose acetate (CA) microspheres, on Vitamin D 3 activity. Isolated rat islets, both free and entrapped in microspheres were treated with Vitamin D 3 . The effects of the vitamin were studied at 3, 6 and 9 days of in vitro cell culture. According to insulin secretory patterns, treatment with Vitamin D 3 of both free and CA entrapped microspheres, increased the insulin output as compared to untreated controls. Such positive effects were confirmed under islet static incubation with glucose at day 6. These results suggest that pancreatic islets can be advantageously treated with anti-oxidising vitamins before implantation, and speculatively, with the help of special delivery systems, throughout the islet cell life span, in the post-transplant time period. r 2003 Elsevier Science Ltd. All rights reserved. Keywords: Polymers; Membrane; Glucose; Insulin; Anti-oxidants 1. Introduction Pancreatic islet cell transplantation might represent the final solution to the therapy of type 1 diabetes mellites (T1DM) as demonstrated by the very promising results obtained by ongoing allograft clinical trials [1]. These have so far shown restoration of euglycemia in 70% of the grafted patients at 2 years of post-transplant follow up. However the islet supply problem is still open, depending upon scarce availability of human organ donors, while immunosuppressive therapy is associated with adverse long-term side effects. To possibly solve the above indicated drawbacks, both alternate tissues as a resource for donor islets, and innovative strategies for islets transplant immunopro- tection are currently being investigated. It is well known that only very few islet xenograft protocols in animals have been proven successful [2]. Immunological reactions, as well as not immune events, such as inflammation or apoptosis, are the main causes for graft failure [3–7]. Recent clinical data from the above mentioned trials, have demonstrated that success of human islet transplantation is largely due to characteristics of the implanted cells (with special regard to number and viability [1]). Although mastered in a few laboratories, microencap- sulation technology, consisting of physical envelopment *Corresponding author. Dipartimento di Chimica e Tecnologia del Farmaco, University di Perugia, via del Liceo, 06100 Perugia, Italy. Tel.: +39-075-5852057; fax: +39-075-5852230. E-mail address: nas@unipg.it (C. Nastruzzi). URL: www.unipg.it. 0142-9612/03/$ - see front matter r 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0142-9612(03)00118-2