Development and in vitro evaluation of chitosan-fucoidan composite nanoparticle delivery system loaded with tetramethylpyrazine for anti-H. pylori therapy

Tetramethylpyrazine (TMP) is a natural compound, and several marketed drugs use TMP for the clinical treatment of neurological diseases. TMP also exhibits antibacterial activity; however, its inhibitory effect on Helicobacter pylori ( H. pylori ) has not been fully explored in the scientific literature. In this study, a nanoparticle drug delivery system (TMP@CS/FU NPs) was developed using the natural polysaccharides chitosan (CS) and fucoidan (FU). CS and FU form a stable framework through electrostatic adsorption, and TMP accumulates within the nanoparticle framework via hydrogen bonds, hydrophobic interactions, and other forces. This results in a core-shell structure, creating stable nanoparticles with an average size of approximately 280 nanometers. The polydispersity index (PDI) ranges from 0.3 to 0.4, and the zeta potential is approximately 15 mV. The drug loading capacity was 33.25%, with an encapsulation efficiency of 9.5%. Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) confirmed the successful encapsulation of TMP. In vitro pharmacological experiments showed that the TMP@CS/FU NPs system effectively inhibited the growth of H. pylori strain SSI, disrupted its structure, affected urease activity, and significantly reduced the expression of key virulence factors linked to H. pylori infection. Additionally, metabolomics analysis provided a deeper understanding of the multi-target and multi-pathway metabolic mechanisms through which TMP@CS/FU NPs influence H. pylori steroid metabolism, amino sugar nucleotide metabolism, arachidonic acid metabolism, and other pathways. This suggests that TMP likely inhibits H. pylori by targeting multiple pathways. These findings reveal the mechanisms by which TMP@CS/FU NPs suppress the growth and proliferation of H. pylori , further confirming the value of this drug delivery system in combating H. pylori . Molecular docking studies revealed that TMP may exert its antibacterial effects by influencing disease-related targets of H. pylori . These findings suggest that the TMP@CS/FU NPs drug delivery system not only significantly enhances the antibacterial activity of TMP but also targets H. pylori through multiple pathways, reducing the risk of H. pylori developing resistance to TMP. This provides a new strategy and research direction for the treatment of H. pylori infections.