Oral delivery of beta-lactamase by Lactococcus lactis subsp. lactis transformed with Plasmid ss80.
The objective was to use normal flora to deliver protein/peptide drugs orally. A probiotic bacterium, Lactococcus lactis subsp. lactis (L. lactis) transformed with Plasmid ss80, which made it able to synthesize and secrete beta-lactamase, a 29 kDa protein, was used as the delivery system for beta-lactamase. Oral absorption of beta-lactamase in rats when delivered by this L. lactis system was investigated. The oral bioavailability of beta-lactamase delivered by 3x10(7) of the L. lactis was equivalent to 209 mU of i.v. dose, and the estimated relative bioavailability was 16.7%. When delivered by beta-lactamase free solution form, the relative oral bioavailability was 4.7%, which increased to 6.0% when co-administered with 3x10(7) of the untransformed L. lactis. The results demonstrated that the L. lactis significantly increased the beta-lactamase oral bioavailability by 2-3-folds (p<0.01), the mean residence time (MRT) by 3-4 times (p<0.01), and the mean absorption time (MAT) by 6-14 times (p<0.01), as compared to the free solution form with/without the untransformed L. lactis. In conclusion, the L. lactis is more efficient in delivering beta-lactamase orally compared with the free solution form. It also provides a sustained delivery mechanism for beta-lactamase. Gene-transformed normal flora may be used as an efficient and sustained delivery system for protein drugs through oral route.
Kaushal
Gagan
G
Biotechnology and Drug Delivery Laboratory, Department of Pharmacy and Administrative Sciences, College of Pharmacy and Allied Health Professions, St. John's University, 8000 Utopia Parkway, Jamaica, NY 11439, USA.
Shao
Jun
J
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D005260:Female; D007408:Intestinal Absorption; D013294:Lactococcus lactis / Q000201:enzymology / Q000235:genetics; D010957:Plasmids; D051381:Rats; D017207:Rats, Sprague-Dawley; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
D001618:beta-Lactamases