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Orally delivered rapamycin is an immunosuppressant that inhibits islet graft rejection in patients treated for type 1 diabetes, but it suffers from poor bioavailability, inconsistent cellular distribution and adverse reactions. Here the authors show that subcutaneous delivery of rapamycin using a polymersome platform allows for control of the drug’s biodistribution and activity on specific immune cells, which changes its mechanism of action from immunosuppression to tolerance, reduces side effects and enhances anti-inflammatory efficacy.
