Biodegradable microsphere-loaded tacrolimus enhanced the effect on mice islet allograft and reduced the adverse effect on insulin secretion.

The adverse effects of tacrolimus have limited the use of this potent immunosuppressive drug in clinical transplantation. To improve the therapeutic effects, we developed a new type of tacrolimus with biodegradable microsphere technology and examined the immunosuppressive effects on allogeneic islet transplantation and the side-effects on insulin secretion in vivo. With a single subcutaneous injection, mouse blood concentrations of tacrolimus (M-FK) carried in biodegradable microspheres remained flat for 2 weeks (only 10 h for conventional tacrolimus). A single subcutaneous administration of 20 mg/kg of M-FK significantly prolonged the survival of islet allografts (MST = 28 days) compared with the control group (MST = 10 days). Series administration of 10 mg/kg of M-FK at 7-day intervals markedly prolonged the survival of islet grafts, and resulted in 60% allograft acceptance. In mice with syngeneic islet transplantations, a single administration of 30 mg/kg of tacrolimus inhibited insulin secretion, whereas a single administration of an equal dosage of M-FK did not. The results suggested that M-FK enhanced the immunosuppressive effects on islet allograft rejection more effectively with reduced side-effects on insulin secretion.