Genetically engineered normal flora for oral polypeptide delivery: dose-absorption response.

Genetically modified Lactococcus lactis (L. lactis), a probiotic bacterium, able to secrete beta-lactamase (29 kDa), was used as a vector for the oral delivery of beta-lactamase to the rats. Three different doses of L. lactis were administered to the rats, and the resulted beta-lactamase oral bioavailability was studied, and compared to the solution form. The oral administration of 1.2 x 10(7), 3 x 10(7), and 8 x 10(7) colony-forming units of L. lactis led to 145, 209, and 364 mU of beta-lactamase absorbed, and the corresponding bioavailability was 8.7%, 15.5%, and 20.8% based on the in vitro production of beta-lactamase by L. lactis. The oral administration of 504 mU and 1008 mU beta-lactamase free solution resulted in 30 and 47 mU absorbed, a bioavailability of 5.9% and 4.7%, respectively. L. lactis significantly (p < 0.01) increased the oral bioavailability compared to the free solution form. A significant (p < 0.01) increase in the MAT value as compared to the solution, demonstrated that L. lactis can be used as a sustained delivery system. In conclusion, there is a linear relationship between L. lactis dose and these absorption PK parameters within L. lactis dose range of the current study.