Lucifer Yellow Permeability Research Articles

In vitro nasal transport across rabbit mucosa: Effect of oxygen bubbling, pH and hypertonic pressure on permeability of lucifer yellow, diazepam and 17 β-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 β-estradiol (E2; MW 272) and estrone (El; MW 270) that was produced from E2 by 17 β-hydroxy-steroid dehydrogenase (17 β-HSD). The low pH increased the permeation of drugs, especially LY. The activity of 17 β-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.

Simultaneous in vitro measurement of intestinal tissue permeability and transepithelial electrical resistance (TEER) using Sweetana-Grass diffusion cells.

A simple modification of the commercially available Sweetana-Grass (S-G) side-by-side diffusion cells, allowing the simultaneous measurement of tissue permeability and transepithelial electrical resistance (TEER), has been described and validated for rat excised, muscle-free intestinal tissue. The TEER-lowering effects of a series of acylcarnitines were shown to be correlated with previously reported in vitro (i.e., membrane perturbation) and in vivo (i.e., absorption enhancement) activity. The TEER-lowering effect of palmitoyl carnitine chloride (PCC) was also shown to be reversible. The effects of PCC on TEER and the permeability of poorly absorbed compounds (cefoxitin and lucifer yellow) were simultaneously determined. Compared to controls (mannitol-treated), PCC immediately produced a rapid drop in colon TEER. By 5 min post-PCC addition, colon TEER was 50% of control; by 10 min post-PCC addition, colon TEER was 17% of control. After a lag of about 5-10 min post-PCC addition, the cefoxitin or lucifer yellow permeability coefficient increased more than 20-fold. The modified S-G cells provide a simple and reproducible method whereby flux and TEER can be simultaneously determined, providing a valuable link between the effect of absorption enhancers on TEER measurements and the increased permeability of poorly absorbed compounds.