Oligoethyleneimine‐Conjugated Hyaluronic Acid Modulates Inflammatory Responses and Enhances Therapeutic Efficacy for Ulcerative Colitis

Abstract Modulation of innate immune responses is a potential strategy for treating inflammatory diseases. Although biogenic polyamines are known as immunomodulatory compounds possessing anti‐inflammatory functions, their biomedical applications have been limited owing to their cytotoxicity. Here, the discovery of an anti‐inflammatory and biocompatible compound is reported, which is a relatively low‐molecular‐weight polyamine, branched oligoethyleneimine (bOEI). Among bOEI molecules, bOEI‐300 strongly suppresses the secretion of pro‐inflammatory cytokines from stimulated primary macrophages by scavenging reactive oxygen species and inhibiting the nuclear translocation of the nuclear factor kappa‐B. Moreover, its polyampholyte‐like conjugate with hyaluronic acid improves the biocompatibility of polyamines and enhanced anti‐inflammatory functions. In a murine ulcerative colitis model, the conjugates enhance therapeutic efficacy by suppressing the production of pro‐inflammatory cytokines. This polyamine‐conjugated biopolymer has enormous potential to treat inflammatory diseases via the modulation of inflammatory responses.