Psoriasis and enzyme therapeutics

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Localized delivery of indoleamine 2,3-dioxygenase (IDO) conjugated microgels reduced psoriatic scores compared to soluble IDO or unconjugated microgels.

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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.

Source: onlinelibrary.wiley.com

*Funding: National Institutes of Health