Transport studies of insulin across rat jejunum in the presence of chicken and 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 filled with Krebs bicarbonate buffer, bubbled with 95% O2/5% CO2 at a fixed flow rate and maintained at 37 degrees C. The permeation of insulin, a lipophilic marker ([7- 3H] testosterone) and a hydrophilic marker (D-[1- 14C] mannitol) was evaluated in the presence of 0.5-1.5 microM 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 and 1:2 was used. In the absence of alpha-chymotrypsin, the permeability coefficient (Papp) 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. Conversely, the permeation of the hydrophilic and lipophilic marker increased with increasing concentrations of CkOVM and DkOVM. In stability studies, the percentage of drug remaining was found to be 2-fold higher at the 1:2 ratio than with the 1:1 ratio of enzyme to inhibitor. This was in agreement with the 2-fold increase in flux values of insulin in the presence of alpha-chymotrypsin and DkOVM at the 1:2 ratio of enzyme to inhibitor. The decrease in permeation of insulin in ovomucoids was unexpected. Marker transport studies indicated that ovomucoids have the potential to modulate transcellular and paracellular permeability. The flux enhancement of insulin in the presence of alpha-chymotrypsin and DkOVM is encouraging. The use of ovomucoids offers potential to enhance oral delivery of insulin and warrants further investigation.
Agarwal
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V
Department of Pharmaceutical Sciences, Texas Tech University HSC, School of Pharmacy, Amarillo 79106, USA.
Nazzal
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S
Reddy
I K
IK
Khan
M A
MA
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002645:Chickens; D002918:Chymotrypsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004372:Ducks; D007328:Insulin / Q000493:pharmacokinetics*; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010059:Ovomucin / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014361:Trypsin Inhibitors / Q000494:pharmacology*
D007328:Insulin; D014361:Trypsin Inhibitors; D010059:Ovomucin; D002918:Chymotrypsin; C117608:alpha-chymotrypsin