Oral Delivery of Chitosan Derivative-Based Nanoparticles Encapsulating Quercetin to Attenuate Intestinal Injury and Regulate Gut Microbiota Dysbiosis in Mucositis Treatment

Abstract

Although the importance of quercetin (QUE) in diets and as food supplements is well-known, the oral utilization of QUE is limited by its instability, poor solubility, and low bioavailability. To overcome these disadvantages, QUE-loaded chitosan derivative-based nanoparticles (QUE-CDNPs) were fabricated, and their ameliorative efficacy against intestinal injury and gut microbiota dysbiosis in chemotherapy-induced mucositis were investigated. The morphology and structural characteristics of the QUE-CDNPs produced showed an average size of about 370.7 nm and a ζ potential of −21.9 mV. It indicated that the QUE encapsulation efficiency in CDNPs reached 71.2%, and the CDNP carrier substantially increased the bioavailability of QUE compared with that of the free QUE in vivo. QUE-CDNP treatment remarkably alleviated the 5-Fu-induced destruction of villus and crypt in the jejunum. In addition, QUE-CDNPs effectively caused an attenuation of the pro-inflammation factors expression and an enhancement of claudin-1 expression in the jejunum, which consequently ameliorated intestinal barrier function. Furthermore, the QUE-CDNP treatment partially reversed the alterations in the intestinal microbiota of mice with 5-Fu-induced mucositis by decreasing the abundance of Bacteroides. These results demonstrate that the use of the QUE-CDNP-delivery system has the potential to improve both the stability and bioavailability and thus the efficacy of quercetin for the treatment of intestinal mucositis.