INFLUENCE OF BILE-SALTS ON THE PERMEABILITY THROUGH THE NASAL-MUCOSA OF RABBITS OF INSULIN IN COMPARISON WITH DEXTRAN DERIVATIVES

The nasal drug absorption and the effect of absorption promoters have been studied in rabbits. Nasal mucosa excised from rabbits was mounted as a flat sheet in an in vitro chamber. The result indicates that the change in the porosity of the membrane by pretreatment with bile salts increased the permeability coefficient of sodium chloride in the nasal membrane. The permeabilities of dextran derivatives were enhanced by pretreatment with sodium glycocholate (GC). The permeability coefficient (P) of fluorescein isothiocyanate diethylaminoethyl dextran (FITC-dextran, DE) was higher than that of FITC-dextran (DT), and P of FITC dextran sulfate (DS) was lower than that of DT with the same molecular weight. Comparing insulin with dextran that is the same molecular weight as insulin, P of insulin induced by the pretreatment with GC was higher than that of hydrophilic dextran. The partition coefficient seemed to have better effect on the nasal membrane transport than the molecular weight of the penetrant.