Local Co-Delivery of Pancreatic Islets and Liposomal Clodronate Using Injectable Hydrogel to Prevent Acute Immune Reactions in a Type 1 Diabetes

Abstract

The purpose of this study was to investigate the effect of locally delivered pancreatic islet with liposomal clodronate (ClodrosomeA (R)) as an immunoprotection agent for the treatment of type 1 diabetes. The bio-distribution of liposomal clodronate in matrigel was checked by imaging analyzer. To verify the therapeutic efficacy of locally delivered islet with liposomal clodronate using injectable hydrogel, four groups of islet transplanted mice (n = 6 in each group) were prepared: 1) the islet group, 2) the islet-Clodrosome group, 3) the islet-Matrigel group, and 4) the islet-Matrigel-Clodrosome group. Immune cell migration and activation, and pro-inflammatory cytokine secretion was evaluated by immunohistochemistry staining and ELISA assay. Cy5.5 labeled liposomes remained in the matrigel for over 7 days. The median survival time of transplanted islets (Islet-Matrigel-Clodrosome group) was significantly increased (> 60 days), compared to other groups. Locally delivered liposomal clodronate in matrigel effectively inhibited the activation of macrophages, immune cell migration and activation, and pro-inflammatory cytokine secretion from macrophages. Locally co-delivered pancreatic islets and liposomal clodronate using injectable hydrogel effectively cured type 1 diabetes. Especially, the inhibition of macrophage attack in the early stage after local delivery of islets was very important for the successful long-term survival of delivered islets.