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 fil...

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Published in:Journal of pharmacy and pharmacology 2001-08, Vol.53 (8), p.1131-1138
Main Authors: Agarwal, Vikas, Nazzal, Sami, Reddy, Indra K., Khan, Mansoor A.
Format: Article
Language:English
Subjects:
Animals
Biological Transport - drug effects
Chickens
Chymotrypsin - pharmacology
Dose-Response Relationship, Drug
Ducks
Insulin - pharmacokinetics
Jejunum - drug effects
Jejunum - metabolism
Male
Ovomucin - pharmacology
Permeability - drug effects
Rats
Rats, Sprague-Dawley
Trypsin Inhibitors - pharmacology
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Summary: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°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 μM duck ovomucoid (DkOVM) or chicken ovomucoid (CkOVM). For stability and permeation of insulin in the presence of α‐chymotrypsin, an enzyme‐to‐inhibitor ratio of 1:1 and 1:2 was used. In the absence of α‐chymotrypsin, the permeability coefficient (Papp) of insulin at pH 7.4 was 0.922 ± 0.168 times 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 α‐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 α‐chymotrypsin and DkOVM is encouraging. The use of ovomucoids offers potential to enhance oral delivery of insulin and warrants further investigation.
ISSN:0022-3573
2042-7158
DOI:10.1211/0022357011776522