Site-dependence and structure-effect relationships for alkylglycosides as transmucosal absorption promoters for insulin

Abstract

Alkylglycoside surfactants have recently been identified as a new type of membrane permeation enhancer. The purpose of this study was to compare the effects of alkylglycosides on buccal, nasal, and rectal absorption, and to examine structure/effect relationships for buccal permeation enhancement. Insulin was used as a model, poorly bioavailable, protein drug, and pharmacologic effect was used as an index of absorption. Octylglucoside and dodecylmaltoside at 5% concentrations had greater enhancing effects on buccal absorption than on nasal or rectal insulin absorption. Dodecylmaltoside increased buccal insulin absorption to some extent at concentrations as low as 1%. There was no consistent relationship between the alkyl chain lengths of the alkylglycosides and their absorption promoting effects, nor between the critical micelle concentrations of the enhancers and their absorption promoting effects. A thioglucosidc and an alkylglucamide increased insulin absorption, but sorbitan monolauratc, an ester, did not.