Localized IDO Delivery via Granular PEG Hydrogel Enhances Therapeutic Control of Psoriasis

Enzyme therapeutics are often limited by poor stability, rapid clearance, and systemic effects that reduce therapeutic efficacy and necessitate high dosing. Enzyme-biomaterial conjugation can address these limitations and improve outcomes by localizing therapeutics at the tissue site of intended action. In particular, indoleamine 2,3-dioxygenase (IDO), a potent immunomodulatory enzyme, has demonstrated therapeutic effectiveness when retained locally at sites of inflammation through fusion to a carbohydrate-binding protein. Here, we report a complementary biomaterial-mediated delivery strategy to prolong retention time and investigate efficacy in an imiquimod-induced model of psoriasis. IDO maintained enzyme activity after bioconjugation to polyethylene glycol maleimide (PEG-MAL) microgels. Localized delivery of IDO-conjugated microgels reduced psoriatic scores compared to soluble IDO or unconjugated microgels. Additionally, fibrotic capsule thickness decreased 30% in the IDO-conjugated microgel group compared to the unconjugated microgel. These findings demonstrate the efficacy of localized IDO delivery via covalent attachment to granular hydrogels, which may serve as a platform for other immunomodulatory enzymes.