Genetically engineered normal flora for oral polypeptide delivery: Dose–absorption response
✍ Scribed by Gagan Kaushal; Jun Shao
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 220 KB
- Volume
- 98
- Category
- Article
- ISSN
- 0022-3549
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✦ Synopsis
Genetically modified Lactococcus lactis (L. lactis), a probiotic bacterium, able to secrete b-lactamase (29 kDa), was used as a vector for the oral delivery of b-lactamase to the rats. Three different doses of L. lactis were administered to the rats, and the resulted b-lactamase oral bioavailability was studied, and compared to the solution form. The oral administration of 1.2 Â 10 7 , 3 Â 10 7 , and 8 Â 10 7 colony-forming units of L. lactis led to 145, 209, and 364 mU of b-lactamase absorbed, and the corresponding bioavailability was 8.7%, 15.5%, and 20.8% based on the in vitro production of b-lactamase by L. lactis. The oral administration of 504 mU and 1008 mU b-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. ß 2009 Wiley-