In vitro nasal transport across rabbit mucosa: Effect of oxygen bubbling, pH and hypertonic pressure on permeability of lucifer yellow, diazepam and 17 beta-estradiol

The effect of pH, oxygen bubbling and hypertonic osmolarity in excised rabbit nasal mucosa on permeation of drugs was examined. For preincubation we used: (i) pH 5.2 saline, pH 7.4 saline and Krebs-Ringer solution (KR); (ii) the absence and presence of oxygen bubbling; and (iii) hypertonic KR. The control was put in KR with oxygen bubbling without preincubation. The permeation of lucifer yellow (LY; MW 521) as a hydrophilic drug and of diazepam (DP; MW 285) as a lipophilic drug and the amount of protein released from tissue were measured after preincubation. Also the enzyme activity in the nasal mucosa was examined by measuring the permeation of 17 beta-estradiol (E2; MW 272) and estrone (E1; MW 270) that was produced from E2 by 17 beta-hydroxy-steroid dehydrogenase (17 beta-HSD). The low pH increased the permeation of drugs, especially LY. The activity of 17 beta-HSD appears to decrease by a low pH more than by bubbling. The protein from the mucosa after preincubation was released in the donor and receiver cells without bubbling irrespective of pH. High osmotic pressure in donor KR solution with bubbling also released more protein in the donor cell compared with a change in pH to 5.2 and 7.4 without bubbling. The results of the released protein amount are in agreement with those of the permeability study, suggesting a morphological change. The low pH increased the permeation of drug, and decreased the enzyme activity in the nasal mucosa without increasing the release of protein from the nasal mucosa compared with the release at pH 7.4. This finding can be applied to nasal absorption of drugs. (C) 1997 Elsevier Science B.V.