Enhancement of intestinal model compound transport by DS-1, a modified Quillaja saponin

DS-1, a modified Quillaja saponin, has recently been shown to promote the absorption of insulin and aminoglycoside antibiotics via the ocular and nasal route. The purpose of this study is to investigate the effect of DS-1 on intestinal permeability, the mechanism of its action, and reversibility of the effect. The permeation-enhancing activity of DS-1 was evaluated in cultured monolayers of the Caco-2 intestinal epithelial cells by examining its effect on the transepithelial electric resistance (TEER) and on transport of mannitol and a model D-decapeptide. Mucosal addition of DS-1 promptly reduced the TEER of the Caco-2 monolayers, and a propensity of recovery of the TEER was observed upon its removal. DS-1 added at 0.01-0.1% (w/v) increased the transports of both mannitol and D-decapeptide in a dose-dependent manner; a relatively "flat" concentration-dependence was seen at 0.1-0.2%. Visualization studies conducted by confocal laser scanning microscopy (CLSM) seem to suggest that DS-1 enhances the Caco-2 permeability mainly via a transcellular route. Histological examination failed to reveal noticeable morphological alterations in the cell monolayers pretreated with DS-1. The integrity of the Caco-2 monolayers, as assessed by their permeability to mannitol, was found to be recoverable following the mucosal pretreatment of DS-1. These results suggest that DS-1 is an efficacious intestinal permeation-enhancing agent with low adverse effect on the epithelial viability and barrier function.