Propylene Glycol Caprylate as a Novel Potential Absorption Enhancer for Improving the Intestinal Absorption of Insulin: Efficacy, Safety, and Absorption-Enhancing Mechanisms.

Sodium caprate (C10) acts as an absorption enhancer. However, the absorption-enhancing effects of compounds with structures similar to C10 have not been characterized. In the present study, insulin was used as a model drug. We examined the effects of C10 and its related compounds on intestinal absorption of insulin using an in situ closed loop in rats. Insulin absorption was significantly enhanced by propylene glycol caprylate (Sefsol-218), a C10-related compound, after large intestinal administration. In addition, activity of lactate dehydrogenase did not increase in the intestinal epithelium in the presence of Sefsol-218 at concentrations equivalent to or lower than 1% (v/v). However, a significant increase in lactate dehydrogenase activity was observed in response to C10. These findings suggested that Sefsol-218 was safer than C10. Furthermore, mechanistic studies showed that increased membrane fluidity and loosening of tight junctions (TJs) might be underlying mechanisms by which this compound improved intestinal absorption of insulin. Furthermore, Sefsol-218 opened TJs by reducing the expression of claudin-4, which is a major TJ protein. These findings suggested that Sefsol-218 effectively enhanced intestinal insulin absorption without causing serious damage to the intestinal epithelium.