Transplantation of pancreatic islets is recognized as a potential curative therapy for TIDM; however, islets are extremely susceptible to the mechanical, hypoxic and immunologic stresses associated with transplantation, causing a high rate of failure. We evaluated a novel technique to improve islet cell survival, using dual nanoporous encapsulation and local delivery of exenatide, a clinically approved drug known to promote islet survival. Islets were microencapsulated with alginate-poly-L-lysine using an electrospray method, then placed inside a nanoporous device which contained a drug delivery chamber. Initial studies were performed to titrate drug diffusion through the nanoporous membrane. Tuning of pore size and application of a PEG coating allowed either burst release or sustained delivery at desired local concentrations (10nM exenatide). Next, we tested the effect of dual encapsulation and local drug delivery on murine islet viability and function in vitro using three groups: (I) unencapsulated islets (control), (II) dual encapsulated islets, (III) dual encapsulated islets + exenatide. Islet morphology and insulin production were assessed over a 14-day period. At day 14, islet viability was compared using dual fluorescent (live/dead) staining. Dispersion of islets occurred in Group I (91%) by day 14, but was minimal in both encapsulated Groups II (17%) and III (9%). Within the encapsulated islet groups, mean islet viability was significantly improved by local delivery of exenatide (Group II vs Group III, P = 0.01). Massive insulin release occurred in group I during the period of maximal cell death. Insulin release from dual encapsulated islets was lower, but was sustained more consistently throughout the culture period. In conclusion, dual islet encapsulation prevented islet dispersion in culture. Local drug delivery of exenatide was achieved using a nanoporous drug chamber and was shown to significantly improve islet viability. Future plans include the implementation of dual encapsulated islets and exenatide for in-vivo studies in mice and dogs, with the ultimate goal of curing human TIDM.

« Back to 2013 American Transplant Congress