Attenuating Oxidative Stress Via Oxalate Ester‐Containing Ferulic Acid‐Based Poly(anhydride‐esters) that Scavenge Hydrogen Peroxide

Ferulic acid (FA) is a naturally occurring, potent antioxidant commonly utilized in biomedical, food, and cosmetic formulations. While effective, FA's instability decreases its efficacy in formulations. Previous work demonstrates stabilization and controlled release of FA when incorporated into a polymer; however, these polymers lack inherent bioactivity, which can be significant in systems being actively impaired by oxidative stress. To address this limitation, oxalate ester linkages are incorporated into the polymer backbone due to their high reactivity toward hydrogen peroxide, a reactive oxygen species precursor. While polymer thermal properties and weight‐averaged molecular weight are similar to previous FA‐based poly(anhydride‐esters), the relative hydrophobicity, as indicated by contact angle measurements, is significantly higher. In vitro release studies indicate that polymer degradation and corresponding release of free FA are not solely dependent on hydrophobicity; despite higher hydrophobicity, these oxalate‐containing polymers degrade faster than previously published, more hydrophilic FA‐based polymers. Moreover, released FA maintains antioxidant activity, whereas the polymer displays hydrogen peroxide scavenging activity. Cytocompatibility studies demonstrate acceptable in vivo use up to 0.01 mg mL −1 . This polymer system offers a two‐pronged approach to attenuate oxidative stress, as both the release product (i.e., FA) and polymer possess radical scavenging activity, rendering it useful for antioxidant applications.