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.
Kaushal
Gagan
G
School of Pharmacy, University of Charleston, 2300 MacCorkle Ave. S.E., Charleston, West Virginia 25304, USA.
Shao
Jun
J
D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D007408:Intestinal Absorption / Q000187:drug effects* / Q000502:physiology; D013294:Lactococcus lactis / Q000235:genetics*; D010455:Peptides / Q000008:administration & dosage* / Q000235:genetics* / Q000493:pharmacokinetics; D019936:Probiotics / Q000008:administration & dosage; D015202:Protein Engineering / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D001618:beta-Lactamases / Q000008:administration & dosage / Q000235:genetics
D010455:Peptides; D001618:beta-Lactamases