Transport studies of insulin across rat jejunum in the presence of chickenand duck ovomucoids

Our aim was to evaluate the transport of insulin across rat jejunum in the presence of ovomucoids and to assess the effect of ovomucoids on intestinal tissue by studying the permeation of a lipophilic and a hydrophilic marker . Rat jejunal segments were mounted in a side-by-side diffusion chamber fil led with Krebs bicarbonate buffer, bubbled with 95 % O-2/5 % CO2 at a fixed flow rate and maintained at 37 degreesC. The permeation of insulin, a lipo philic marker ([7-H-3] testosterone) and a hydrophilic marker (D-[1-C-14] m annitol) was evaluated in the presence of 0.5-1.5 muM duck ovomucoid (DkOVM ) or chicken ovomucoid (CkOVM). For stability and permeation of insulin in the presence of alpha -chymotrypsin, an enzyme-to-inhibitor ratio of 1:1 an d 1:2 was used. In the absence of alpha -chymotrypsin, the permeability coe fficient (P-app) of insulin at pH 7.4 was 0.922 +/- 0.168 x 10(-7) cm s(-1) , which decreased with increasing concentrations of DkOVM or CkOVM. Convers ely, the permeation of the hydrophilic and lipophilic marker increased with increasing concentrations of CkOVM and DkOVM. in stability studies, the pe rcentage of drug remaining was found to be 2-fold higher at the 1:2 ratio t han with the 1:1 ratio of enzyme to inhibitor. This was in agreement with t he 2-fold increase in flux values of insulin in the presence of alpha -chym otrypsin and DkOVM at the 1:2 ratio of enzyme to inhibitor. The decrease in permeation of insulin in ovomucoids was unexpected. Marker transport studi es indicated that ovomucoids have the potential to modulate transcellular a nd paracellular permeability. The flux enhancement of insulin in the presen ce of alpha -chymotrypsin and DkOVM is encouraging. The use of ovomucoids o ffers potential to enhance oral delivery of insulin and warrants further in vestigation.