Screening of various glycosidases for the synthesis of octyl glucoside

Thirteen glycosidases of microbial origin and almond beta-glycosidase were assayed in octanol/DMF (80:20, v/v), using a combination of hydrolysis, transglycosylation, and condensation reactions, in order to assess their potential for the production of alkyl glucosides. The two mesophile enzymes were highly impaired by the organic media. Three of the 11 thermophile enzymes gave interesting results in the hydrolysis and transglycosylation reactions, but they were highly inhibited by glucose. This made their use in a condensation reaction less interesting than the use of almond beta-glucosidase, which has a lower activity but shows less inhibition by the glucose.     

In vitro assessment of alkylglycosides as permeability enhancers

A series of alkylglycosides has been evaluated on human cell lines to determine its ability to open cellular tight junctions. Alkylglycosides were applied to cell monolayers; the resulting change in resistance was determined by transepithelial electrical resistance measurements. Change in resistance across cell monolayers is an indieation of tight junction activation, whereas subsequent increase in resistance signifies monolayer recovery. Of the 13 alkylglycosides tested, 4 caused irreversible solubilization of cell membranes, 5 allowed a partial recovery of the monolayer after a relatively rapid reduction in resistance, and 4 induced a decrease in resistance with more complete cell recovery. Alkylglycosides allowing extensive cell recovery after removal may indieate tight junctions activity dominance over membrane fluidity Repeated application of alkylglycosides for 6 hours lowered resistance across cells, which returned to near-normal values after a recovery period of 48 hours. A model dye was transported across the cell monolayer only in the presence of an alkylglycoside, although recovery of cells was incomplete. Activity of the alkylglycosides was unrelated to either the carbon chain length or to the carbohydrate moiety. A direct correlation was established between the concentration of applied alkylglycoside and reduction in resistance over a constant time period. Dodecylmaltoside and oetylglucoside were found to be optimal in decreasing resistance at low concentrations and allowing significant recovery of cells. Therefore these 2 alkylglycosides may be useful in facilitating drug transport across biological membranes. Published: October 19, 2001.