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Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug

Paper ID Volume ID Publish Year Pages File Format Full-Text
6315 480 2013 10 PDF Available
Title
Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug
Abstract

Immuno-isolation of islets has the potential to enable the replacement of pancreatic function in diabetic patients. However, host response to the encapsulated islets frequently leads to fibrotic overgrowth with subsequent impairment of the transplanted grafts. Here, we identified and incorporated anti-inflammatory agents into islet-containing microcapsules to address this challenge. In vivo subcutaneous screening of 16 small molecule anti-inflammatory drugs was performed to identify promising compounds that could minimize the formation of fibrotic cell layers. Using parallel non-invasive fluorescent and bioluminescent imaging, we identified dexamethasone and curcumin as the most effective drugs in inhibiting the activities of inflammatory proteases and reactive oxygen species in the host response to subcutaneously injected biomaterials. Next, we demonstrated that co-encapsulating curcumin with pancreatic rat islets in alginate microcapsules reduced fibrotic overgrowth and improved glycemic control in a mouse model of chemically-induced type I diabetes. These results showed that localized administration of anti-inflammatory drug can improve the longevity of encapsulated islets and may facilitate the translation of this technology toward a long-term cure for type I diabetes.

Keywords
Anti-inflammatory drugs; Curcumin; Encapsulated islets; Diabetes; Fibrotic overgrowth; Host response
First Page Preview
Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 34, Issue 23, July 2013, Pages 5792–5801
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering