Drug Discov Ther. 2009;3(5):228-233.

Vaginal delivery of protein drugs in rats by gene-transformed Lactococcus lactis.

Kaushal G, Shao J


A probiotic bacterium, Lactococcus lactis subsp. lactis (L. lactis) transformed with plasmid ss80, which made it capable of synthesizing and secreting β-lactamase, a 29 kDa protein, was used to deliver β-lactamase via vaginal route. The vaginal absorption of β-lactamase in rats was studied when delivered by this L. lactis system and compared to the β-lactamase solution with or without the untransformed L. lactis. The vaginal administration of 1.2 × 107, 3 × 107, and 8 × 107 colony forming units (cfu) of L. lactis resulted in the amount absorbed of 77, 194, and 216 mU, with the respective doses. Cmax, mean retention time and mean absorption time of β-lactamase were also increased with the increase in the cfu of L. lactis administered. These results have demonstrated that L. lactis can significantly increase (p < 0.01) the β-lactamase vaginal absorption as compared to the β-lactamase solution, which is probably due to the adhesion of L. lactis to and continuous synthesis and delivery of β-lactamase directly to the vaginal mucosa. In conclusion, transformed normal flora may be an efficient method to deliver protein drugs through the vaginal route.

KEYWORDS: Lactococcus lactis, β-lactamase, normal flora, protein delivery, vaginal, pharmacokinetics

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