EFFECT OF A CONJUGATED BILE-SALT ON THE PULMONARY ABSORPTION OF INSULIN IN RATS

Pulmonary delivery of insulin with sodium glycocholate (NaGC) as the a bsorption promoter has been investigated using intratracheal instillat ion method. The absolute bioavailability of insulin solution at a dose level of 1 U kg-1 was found to be 78.8% and 9.1% respectively in the presence and absence of 20 mM NaGC, representing a 9-fold increase. Si gnificantly enhanced hypoglycemic effects were also observed following intratracheal administration of 1 U kg-1 insulin with NaGC. The pharm acological availability values were found to be 11.08, 18.97, 21.16, 2 3.37, and 23.44% in the presence of 0, 5, 10, 20 and 30 mM of NaGC, re spectively. On the other hand, Tween 80, at a concentration of 20 mM, resulted in a pharmacological availability of only 16.04% while both s urfactants exhibited considerable reductions in the air-water interfac ial tension. Histological studies failed to reveal any observable alte ration in the epithelial integrity even at 30 mM NaGC concentration. T he mechanisms of bile salt-mediated pulmonary insulin absorption have therefore been postulated to be a combination of a number of factors i ncluding dissociation of insulin oligamers, dilation of pulmonary epit helial tight junctions, surface tension reduction, aminopeptidase inhi bition, and ciliostatic effect.