Development of a Water‐Dispersible Supramolecular Complex of Polyphenol with Polypeptides for Attenuation of the Allergic Response using a Mechanochemical Strategy

The prevalence of allergic disorders has increased worldwide in recent decades. Polyphenols, including resveratrol and curcumin, are posited to have potential as therapeutic agents for allergy; however, their use has been limited by poor water solubility. Accordingly, a highly concentrated, water dispersible, supramolecular complexes of polyphenols with polypeptides (poly‐L‐lysine, poly‐γ‐glutamic acid) and gelatin using high‐speed vibration milling are developed. The complex exhibits resistance to photobleaching and thermal radiation. Treatment of a rat basophilic leukemia cell line (RBL‐2H3) with polypeptide complexes containing resveratrol is suppressed allergic responses in vitro. Moreover, aerosolized administration of polypeptide complexes demonstrates excellent bioavailability and inhibition of immediate hypersensitivity reactions in ear tissue in vivo. Furthermore, the method avoids the use of organic solvent and therefore reduces undesirable biological responses. The complex of polyphenols with polypeptides are prepared via a mechanochemical approach using a ball milling. The methodology is enabled to provide highly concentrated dispersion of polyphenol with excellent stability against long‐term duration and thermal stress. In addition, the complex of resveratrol with poly‐γ‐glutamic acid is exhibited excellent antiallergic effects in vivo.