Oral delivery of β-lactamase by Lactococcus lactis subsp. lactis transformed with Plasmid ss80

Abstract

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 β-lactamase, a 29 kDa protein, was used as the delivery system for β-lactamase. Oral absorption of β-lactamase in rats when delivered by this L. lactis system was investigated. The oral bioavailability of β-lactamase delivered by 3 × 10 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 β-lactamase free solution form, the relative oral bioavailability was 4.7%, which increased to 6.0% when co-administered with 3 × 10 7 of the untransformed L. lactis. The results demonstrated that the L. lactis significantly increased the β-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 β-lactamase orally compared with the free solution form. It also provides a sustained delivery mechanism for β-lactamase. Gene-transformed normal flora may be used as an efficient and sustained delivery system for protein drugs through oral route.