Mannose-modified Prunus persica kernel protein nanoparticles loading baicalin coated with Lycium barbarum polysaccharide for ulcerative colitis treatment

Baicalin (Ba) is a promising anti-inflammatory agent for treating ulcerative colitis (UC), but its efficacy is constrained by poor solubility and colon-targeting efficiency. Lycium barbarum polysaccharide (LBP), an anionic polysaccharide, not only restores gut microbiota dysbiosis but also exhibits excellent upper gastrointestinal stability and biocompatibility, making it a candidate for developing colon-targeted carriers. In this paper, the polymeric nanoparticles (Ba@MP/LBP NPs) were constructed using LBP, mannose, and Prunus persica kernel protein (PKP) for targeted delivery of baicalin to enhance its efficacy in UC treatment. The obtained Ba@MP/LBP NPs possessed core-shell spherical morphology, narrow particle-size distribution (∼230 nm), negative surface charge (−33.89 mV), and excellent baicalin encapsulation (94.26 %). With the aid of the LBP coating, Ba@MP/LBP NPs can tolerate upper gastrointestinal disturbances and transport Ba@MP NPs into colon, thereby facilitating baicalin uptake by inflammatory macrophages via mannose receptor-mediated endocytosis. Furthermore, the LBP coating strengthened Ba@MP NPs' ability to regulate the intestinal flora; hence, Ba@MP/LBP NPs can restore gut microbiota balance while suppressing pro-inflammatory factor secretion and oxidative stress, ultimately alleviating UC. More importantly, Ba@MP/LBP NPs exhibited favorable biosafety. Overall, this work is the first attempt to employ LBP and PKP as colon-targeting carriers, providing a promising nanomedicine for UC therapy.