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 [(14)C]-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 [(14)C]-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.