Lignin nanoparticles-stabilized Pickering emulsions for delivery of curcumin: Gastrointestinal release, gut microbiota modulation and in vivo intestinal responses.

Hydrophobic nutraceuticals such as curcumin are highly promising for functional food applications, but their poor aqueous dispersibility, limited gastrointestinal stability, and low oral bioavailability greatly restrict their efficacy. Thus, it is important to develop food-grade delivery systems that can improve their gastrointestinal fate and post-digestion functionality. In this study, lignin nanoparticles were fabricated using betaine-lactic acid deep eutectic solvent-assisted anti-solvent self-assembly strategy. The resulting lignin nanoparticles were then used as particulate emulsifiers to form and stabilize curcumin-loaded Pickering emulsions. The optimized LNP-7.5 particles showed favorable colloidal properties, with a SPAN value of 0.812 and a ζ-potential of -54.47 mV. The corresponding curcumin-loaded Pickering emulsion achieved an encapsulation efficiency of 81.65% and loading capacity of 7.03%. It also exhibited favorable antioxidant performance, with ABTS and DPPH radical scavenging activities exceeding 90% and 60%, respectively. Simulated digestion revealed the gastrointestinal-responsive release profile, with limited curcumin release under gastric conditions after 6 h (31.1%) but markedly higher release under small intestinal conditions (69.8%). During in vitro fecal fermentation, digested Cur-LNP-PEs promoted short-chain fatty acid production. Repeated oral administration in mice was well tolerated and modulated colonic redox- and inflammation-related gene expression. Moreover, 16S rRNA gene sequencing revealed a significant overall difference in gut microbial community composition among the five groups. Overall, the optimized delivery system exhibited good encapsulation properties, pH- and digestion-dependent release, and formulation-dependent intestinal and microbial responses, supporting its potential for oral delivery of hydrophobic nutraceuticals.