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 ocula r and nasal route. The purpose of this study is to investigate the eff ect of DS-1 on intestinal permeability, the mechanism of its action, a nd reversibility of the effect. The permeation-enhancing activity of D S-1 was evaluated in cultured monolayers of the Caco-2 intestinal epit helial cells by examining its effect on the transepithelial electric r esistance (TEER) and on transport of mannitol and a model D-decapeptid e. Mucosal addition of DS-1 promptly reduced the TEER of the Caco-2 mo nolayers, and a propensity of recovery of the TEER was observed upon i ts 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 relative ly ''flat'' concentration-dependence was seen at 0.1-0.2%. Visualizati on studies conducted by confocal laser scanning microscopy (CLSM) seem to suggest that DS-1 enhances the Caco-2 permeability mainly via a tr anscellular route. Histological examination failed to reveal noticeabl e morphological alterations in the cell monolayers pretreated with DS- 1. The integrity of the Caco-2 monolayers, as assessed by their permea bility to mannitol, was found to be recoverable following the mucosal pretreatment of DS-1. These results suggest that DS-1 is an efficaciou s intestinal permeation-enhancing agent with low adverse effect on the epithelial viability and barrier function.