Quantitative evaluation of the gastrointestinal absorption of protein into the blood and lymph circulation.
In order to investigate the fate of orally administered proteins, the absorption of ovalbumin (OVA) from the gastrointestinal tract into both the blood and lymph circulation was quantitatively evaluated. After oral administration, a significant amount of intact OVA was detected in both the plasma and the lymph fluid by means of a two-site enzyme immunoassay. The extent of absorption into the plasma, calculated from the area under the plasma concentration versus time curve of OVA after oral and intravenous administration, was only 0.007-0.008% of the dose. This value is extremely low compared to that after nasal administration, showing the stronger barrier function of the gastrointestinal tract against the invasion of macromolecular proteins into the body. The extent of absorption into the lymph was dose-dependent (0.0007-0.002% of dose), and a higher dose leads to a higher fraction of OVA absorbed into the lymph. Moreover, it was demonstrated that not only the small intestine but also the stomach can absorb OVA. OVA absorbed from the stomach was transferred almost exclusively to the blood circulation, which suggests different mechanisms and/or routes of absorption between the stomach and the small intestine. In order to improve the low oral absorption, OVA was incorporated in liposomes and administered orally. Although the effect of liposomes was not significant, it increased OVA absorption into both the plasma and lymph by about 2 to 3-fold. It was considered that the liposomes suppressed the enzymatic degradation of OVA and released it slowly in the gastrointestinal tract.
Tsume
Y
Y
Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
Taki
Y
Y
Sakane
T
T
Nadai
T
T
Sezaki
H
H
Watabe
K
K
Kohno
T
T
Yamashita
S
S
D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D007408:Intestinal Absorption; D008196:Lymph / Q000378:metabolism*; D008297:Male; D010047:Ovalbumin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar
D001798:Blood Proteins; D010047:Ovalbumin