Enhancement of Intestinal Model Compound Transport by DS-1, a Modified Quillaja Saponin

Abstract

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.

Role of Caco-2 Cell Monolayers in Prediction of Intestinal Drug Absorption

“…The CCM are routinely employed in investigating the impact of excipients used in delivery systems for enhancement of bioavailability of the drug and for the mechanistic absorption‐enhancer studies (106, 107). Chao et al (108) evaluated the permeation enhancing activity of DS‐1 (a modified Quillaja saponin) in CCM by examining its effect on the TEER and on transport of mannitol and a model d ‐decapeptide. DS‐1 added at 0.01–0.1% (w/v) increased the transports of both mannitol and d ‐decapeptide in a dose‐dependent manner mainly via a transcellular route.…”

Allergenic Potency of Spices: Hot, Medium Hot, or Very Hot

“…This molecular size corresponds to the size of molecules, which are relevant for sensitization and IgE binding in spice allergy. Moreover, plants may contain detergent substances like saponin, which also affect the epithelial barrier [43]. …”

Biologically and Pharmacologically Active Saponins from Plants: Recent Advances

“…This compound could be a good drug absorption-promoting agent. DS-I was shown highly efficious in enhancing intestinal permeability with reduced toxicity making it a good absorption-enhancing agent to be coformulated with orally delivered drugs [38].…”