Exosome-mediated insulin delivery for the treatment of diabetes mellitus

Abstract

Exosomes are membrane-bound extracellular nanovesicles of 30-150 nm released by almost all cell types. Since they were discovered in 1983, numerous studies yielded clear evidences that exosomes serve as essential messengers for hundreds of biological-signaling processes as well as in pathological processes. In consequence of the discovery of exosomal natural functions, a wide range of applications have been developed in several fields of study, especially in drug delivery for therapeutic use. Following this growing stream of study, the aim of this work was to test the efficiency of exosome-mediated human insulin delivery using exosomes extracted from three different cell lines: hepatocellular carcinoma (HepG2); primary dermal fibroblasts (HDFa) and pancreatic β cells (RIN-m); all related to the production and/or the ability to sense insulin and, consequently regulate glucose levels in the extracellular medium. The obtained results revealed that the optimal loading efficiency was achieved by a 200 V electroporation, in comparison to an incubation at room temperature. Moreover, the maximum in vitro exosome uptake was reached after 6 h of incubation with loaded exosomes, and lightly decrease 24 h after adding the exosomes. Furthermore, glucose quantification assays revealed that exosome-mediated incorporation of insulin present significative differences in HDFa and HepG2 cells, enhancing the transport in HDFa, in comparison with free human insulin effect in the regulation of extracellular glucose levels. On the other hand, no significative differences were found between both treatments in RIN-cells. Hence, the results suggest that exosomes could be a potentially valuable tool for a biocompatible and stable insulin delivery as part of a future treatment of diabetes mellitus.