In vitro interactions between the oral absorption promoter, sodium caprate (C-10) and S-Typhimurium in rat intestinal ileal mucosae

Purpose. The medium chain fatty acid, sodium caprate (C-10), is a promising oral drug delivery agent that may promote permeability of peptides through increasing paracellular permeability of the intestinal epithelium. One safety concern is that it may permit co-absorption of by-stander agents including pathogens. The purpose of this in vitro study was to examine the effects of C-10 on rat intestinal ileal mucosae in the presence of co-administered Salmonella typhimurium in a low volume vertical Ussing chamber. Methods. C-10 or S. typhimurium was added to rat ileal mucosae mounted in chambers and the flux of the paracellular flux of [C-14]-mannitol examined. S. typhimurium adherence and uptake by ileal mucosae was also examined by counting. Bacterial growth curves were assessed in the presence of C-10. Minimum inhibitory- and bacteriocidal concentrations of C-10 were determined against a range of bacteria. Results. Apical addition of either C-10 or S. typhimurium to rat ileal mucosae mounted in modified diffusion chambers significantly increased the flux of [C-14]-mannitol in a concentration-dependent fashion. Co-exposure with increasing concentrations of C-10 attenuated the Salmonella-induced increase in mannitol flux. Histological evaluation revealed that C-10 inhibited both adhesion and invasion of S. typhimurium to intestinal mucosae. Short term bacterial growth studies in the presence of C-10 showed evidence of concentration-dependent inhibition. C-10 was bacteriocidal in mM concentrations against S. typhimurium and selected gram positive and negative bacteria. Conclusions. C-10 does not promote the permeation of a common bacterium across isolated intestinal tissue upon acute co-exposure. It prevents S. typhimurium attachment to epithelia and impedes growth of a range of different bacterial strains.