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.

Co-encapsulation of Egg-White-Derived Peptides (EWDP) and Curcumin within the Polysaccharide-Based Amphiphilic Nanoparticles for Promising Oral Bioavailability Enhancement: Role of EWDP

“…12−14 However, the complicated preparation process, limited formation mechanism understanding, and related economic and safety issues (e.g., chemical synthesis and high-energy input) have all placed severe restrictions on the commercial applications. 15,16 Therefore, rational design of facile food-derived material-based co-delivery systems would be essential for the combinational usage of diverse nutraceuticals with different polarities in the food industry and related healthcare fields.…”

“…17 (CMCS), a typical nontoxic chitosan derivative, could effectively improve the oral bioavailability of nutrients via the excellent mucoadhesive property. 16,19 Besides, CMCS exhibits better biocompatibility and water solubility (especially in a neutral or basic environment) than the native chitosan due to the abundant hydrophilic groups on the glucose backbones (e.g., carboxyl group). 20 Thus, developing chitosan derivative− cyclodextrin-based oral co-delivery systems for hydrophilic and hydrophobic nutraceuticals has received increasing attention from all over the world.…”

“…With the rapid development of the layer-by-layer self-assembly concept, numerous researchers have proved that multiple hydrophilic and hydrophobic components could be placed in different regions within a single system to achieve co-delivery . Besides, the co-delivery of various components (e.g., resveratrol, vitamin C, catechin, and quercetin) could exert better bioactivity with admirable controlled release properties. − However, the complicated preparation process, limited formation mechanism understanding, and related economic and safety issues (e.g., chemical synthesis and high-energy input) have all placed severe restrictions on the commercial applications. , Therefore, rational design of facile food-derived material-based co-delivery systems would be essential for the combinational usage of diverse nutraceuticals with different polarities in the food industry and related healthcare fields.…”

“…Accordingly, γ-cyclodextrin (γ-CD), a food-grade amphiphilic polysaccharide, possesses the ideal hydrophobic cavity, which could easily form inclusion with various liposoluble compounds via host–guest interactions. Unfortunately, the poor mucoadhesive properties have greatly hindered the γ-CD applications for numerous nutraceuticals’ bioavailability improvements. , Coincidently, carboxymethyl chitosan (CMCS), a typical nontoxic chitosan derivative, could effectively improve the oral bioavailability of nutrients via the excellent mucoadhesive property. , Besides, CMCS exhibits better biocompatibility and water solubility (especially in a neutral or basic environment) than the native chitosan due to the abundant hydrophilic groups on the glucose backbones (e.g., carboxyl group) . Thus, developing chitosan derivative–cyclodextrin-based oral co-delivery systems for hydrophilic and hydrophobic nutraceuticals has received increasing attention from all over the world. , …”

Fermented Jussara: Evaluation of Nanostructure Formation, Bioaccessibility, and Antioxidant Activity

“…Besides that, the microbiota composition differs between individuals, and its modulation is closely linked to several physiological mechanisms. This modulation can be performed by probiotic microorganisms present or added to food and composing the human intestinal microbiota ( Round and Mazmanian, 2009 ; Guergoletto et al, 2016 ; Zhang et al, 2016 ; Braga, Mesquita et al, 2018 ; Yan et al, 2018 ; Li et al, 2019 ; Santamarina et al, 2019 ; Yan et al, 2021 ). Intestinal bacteria are known to be equipped with a wide variety of enzymes capable of hydrolyzing various glucosides.…”