V. Agarwal et al., Transport studies of insulin across rat jejunum in the presence of chickenand duck ovomucoids, J PHARM PHA, 53(8), 2001, pp. 1131-1138
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.