Tannin-chitosan composite nanoparticles as potencial nanomedicine to prevent urinary tract infections

Introduction. Naturally occurring renewable resources that inhibit microbial adhesion are important alternatives to antibiotics and may help stem the alarming increase in drug resistant bacteria. Bacterial invasion of gut... [ view full abstract ]

Introduction. Naturally occurring renewable resources that inhibit microbial adhesion are important alternatives to antibiotics and may help stem the alarming increase in drug resistant bacteria. Bacterial invasion of gut epithelial cells (enterocytes) provides a mechanism by which pathogens are protected from complements, antibodies, and other immune defense molecules, which in turn, allows the pathogens to colonize and persist in the gut. We have invented novel composite biomaterial comprising formulations of tannin, extracted from cranberries (fruit, juice or press cake), and chitosan, manufactured from shrimp shells. The composites are versatile and can be formulated into useful biomaterials, such as nanoparticles, 3-dimensional foams, and films. Methods. Chitosan binds to negatively charged tannins by an electrostatic interaction driven by its positively charged amino group. This interaction allows developing stable hybrid nanoparticles via ionotropic gelation with tripolyphosphate (TPP), suitable as a therapeutic controlled release system for urinary tract infections. We study the effect of cranberry tannin-chitosan composite nanoparticles on the invasion of Caco-2 cells by Uro-pathogenic Escherichia coli (UPEC) strain 5011, supplied by the UW-University Hospital (Madison, WI, USA). Results. Results of a dose-response experiment indicate the cranberry tannin-chitosan composite nanoparticles significantly reduced invasion of Caco-2 cells by extra-intestinal pathogenic E. coli (ExPEC). The nanoparticles significantly inhibited the ability of the pathogen to invade the Caco-2 cells by 40%, 80% and 96% at a total polyphenolic concentration of 0.2 µg, 0.5µg and 0.75µg GAE/ml (respectively). Discussion. Figure shows scanning electron micrographs exploring the effect of tannin-chitosan composite nanoparticles on ExPEC surface structures that are involved in cell adhesion and subsequent inhibition of invasion of intestinal epithelial cells in vitro. When the pathogen was exposed to the tannin-chitosan composite nanoparticle material (Fig. C), extensive coating and cross-linking on multiple bacteria was seen (Fig. B), compared to control (Fig. A). Results suggest the cranberry tannin-chitosan composite nanoparticles physically coat the surface virulence factors of ExPEC, which in turn prevents invasion of the intestinal epithelial cell.