Biocompatible Chitosan-Based Nanoparticles for the Delivery of <i>Lactobacillus johnsonii</i> Lipoteichoic Acid: Enhancing Stability and Biofunctional Properties

Lipoteichoic acid (LTA), a component of the Gram-positive bacterial cell wall, exhibits potent immunomodulatory properties. However, it is highly unstable and susceptible to degradation under gastrointestinal conditions, which limits its in vivo functional application. In this study, LTA from the<i>Lactobacillus johnsonii</i> was encapsulated into chitosan-tripolyphosphate (CS-TPP) nanoparticles for the first time, establishing a robust delivery system. The resulting LTA@CS-TPP nanoparticles displayed uniform nano size, favorable stability, high encapsulation efficiency, and sustained release behavior. Simulated digestion assays demonstrated that nanoencapsulation effectively protected LTA from gastric degradation and enabled controlled release in the intestinal phase. Cellular experiments showed that LTA@CS-TPP enhanced antioxidative stress defenses, reduced intracellular ROS levels, and alleviated LPS-induced inflammatory injury. Immunofluorescence analysis further revealed that LTA@CS-TPP significantly suppressed NF-κB activation and nuclear translocation, suggesting interference with the TLR₄/MyD88/NF-κB signaling cascade. Compared with free LTA, nanoencapsulation not only preserved but also amplified its bioactivity, whereas blank CS-TPP nanoparticles exerted minimal effects. Collectively, these findings provide the first evidence of chitosan-based nanoencapsulation of LTA and highlight its potential as a bioactive delivery platform for inflammation modulation, laying the groundwork for future oral administration studies with promising applications in functional foods and therapeutic strategies.