Co-encapsulation of Beta Cells and Nanoparticles Containing GLP-1 Greatly Improves Insulin Secretion in Alginate-Based Bioartificial Pancreas

Abstract

The bioartificial pancreas presents a promising methodology to treat diabetes. However, this approach is still associated with a high rate of graft failure caused by poorly functioning cells. The incretin effect of glucagon like peptide-1 (GLP-1) make this peptide an attractive therapeutic agent to improve the success of transplantation of encapsulated beta cells. In present work, we developed a novel model based on the co-encapsulation of beta cells with nanoparticles containing GLP-1 on alginate hydrogels, allowing its delivery and action in the specific target, the beta cells. INS-1E beta cells were co-encapsulated with poly(lactide-co-glycolide) (PLGA) nanoparticles containing GLP-1 in alginate and were maintained in culture aiming to evaluate the performance of our drug-delivery system and the influence of GLP-1 in cellular performance. PLGA nanoparticles showed an average size of 169.3 nm, a polydispersity index of 0.05 and an average zeta-potential of −24.3 mV. The average association efficiency of GLP-1 was 65.4% and the in vitro release test showed 71% of GLP-1 delivery after 7 days. The presence of nanoparticles led to increased cellular metabolic activity and 8-fold higher insulin levels. Our results reveal a promising approach to ensure the proper delivery and action of GLP-1 in encapsulated beta cells, ensuring its viability.