Butyrate‐Loaded Chitosan/Hyaluronan Nanoparticles: A Suitable Tool for Sustained Inhibition of ROS Release by Activated Neutrophils

• Published in: Macromolecular bioscience 2017-11, Vol.17 (11), p.n/a
• Main Authors: Sacco, Pasquale, Decleva, Eva, Tentor, Fabio, Menegazzi, Renzo, Borgogna, Massimiliano, Paoletti, Sergio, Kristiansen, Kåre Andre, Vårum, Kjell Morten, Marsich, Eleonora
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammatory agents; butyrate; Butyrates - pharmacology; Cell Adhesion - drug effects; Chitosan; Chitosan - pharmacology; chitosan/hyaluronan nanoparticles; Controlled release; Drug Liberation; Endocytosis - drug effects; Fatty acids; Fibronectins - pharmacology; human neutrophils; Humans; Hyaluronic acid; Hyaluronic Acid - pharmacology; Hydrogen Peroxide - metabolism; inflammation; Inflammatory bowel diseases; Inflammatory diseases; Injury prevention; Internalization; Intestine; Leukocytes (neutrophilic); Lymphocytes B; Mucins - metabolism; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Neutrophil Activation - drug effects; Neutrophils; Neutrophils - drug effects; Neutrophils - metabolism; Reactive oxygen species; Reactive Oxygen Species - metabolism; Stability; Superoxides - metabolism; Sus scrofa; Time dependence; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.201700214

Tissue damage caused by excessive amounts of neutrophil‐derived reactive oxygen species (ROS) occurs in many inflammatory diseases. Butyrate is a short‐chain fatty acid (SCFA) with known anti‐inflammatory properties, able to modulate several neutrophil functions. Evidence is provided here that butyrate inhibits neutrophil ROS release in a dose and time‐dependent fashion. Given the short half‐life of butyrate, chitosan/hyaluronan nanoparticles are next designed and developed as controlled release carriers able to provide cells with a long‐lasting supply of this SCFA. Notably, while the inhibition of neutrophil ROS production by free butyrate declines over time, that of butyrate‐loaded chitosan/hyaluronan nanoparticles (B‐NPs) is sustained. Additional valuable features of these nanoparticles are inherent ROS scavenger activity, resistance to cell internalization, and mucoadhesiveness. B‐NPs appear as promising tools to limit ROS‐dependent tissue injury during inflammation. Particularly, by virtue of their mucoadhesiveness, B‐NPs administered by enema can be effective in the treatment of inflammatory bowel diseases. Chitosan/hyaluronan nanoparticles are developed for the controlled release of butyrate, an anti‐inflammatory short‐chain fatty acid that inhibits neutrophil production of tissue‐damaging reactive oxygen species (ROS). Butyrate‐loaded nanoparticles (B‐NPs) sustain the inhibitory effect, otherwise short‐lived, of butyrate and exhibit additional features: inherent ROS scavenger activity, resistance to neutrophil uptake, and mucoadhesive properties. B‐NPs appear a promising tool against ROS‐dependent damage during inflammation.