Development of tryptophan-modified chitosan-based nanorelease system: universal encapsulation and targeted delivery of hydrophilic and hydrophobic bioactive compounds

This study successfully constructed an amphiphilic universal nanodelivery system (Trp-CS-PC) by modifying chitosan (CS) with hydrophobic L-Trp and dynamically self-assembling it with pectin (PC). This system achieved efficient and universal encapsulation of hydrophilic bovine collagen peptides (BCP) and hydrophobic curcumin (CUR) (encapsulation efficiency: BCP, 92.2±3.1%; CUR, 73.4±4.5%). Mechanistic studies indicate that the hydrophilic backbone in Trp-CS-PC fixes BCP through hydrogen bonding networks, while the hydrophobic microdomain stabilizes CUR through π-π stacking interactions. Trp-CS and PC formed a core-shell structure via pH-responsive ionic crosslinking, which maintained a tight network in the gastric environment, significantly reducing the release rates of BCP and CUR in gastric fluid (BCP: 18.23±1.05%; CUR: 36.56±2.17%). Trp modification significantly improved the solubility (5.95±0.38   mg/mL) and mucosal adhesion of CS, making this delivery system possess excellent storage stability (size variation <5% within 28 days) and intestinal retention ability (cumulative release of BCP and CUR <59% after gastrointestinal digestion). Furthermore, in vitro activity evaluation results showed that the biological activity retention of BCP and CUR delivered by Trp-CS-PC was significantly higher than that of the control group (P<0.05) . This study provides new ideas and strategies for the research and application of universal oral delivery systems for hydrophilic and hydrophobic bioactive substances.