Oral delivery is the most common way to administer a drug, but it’s not always the most effective. Sometimes very little of the drug a patient swallows ends up being absorbed (1). Oral drugs with low permeability must be given in doses ten to thirty times higher than when delivered intravenously to bring about the intended therapeutic effects. This causes off-target side effects and makes drug manufacturing more expensive. 

In a recent study published in Science Advances, Diptiman Choudhury, a biochemist at the Thapar Institute of Engineering and Technology, developed a creative method for increasing a medication’s chances of being metabolized: transforming bacteria into a drug-transporting boat (2).

Choudhury and his team of researchers created a “bacterioboat” system that encapsulates drug-loaded nanoparticles in the biofilm coating of L. reuteri  bacteria. This biofilm contains sugars and mucus-binding proteins that enable the therapeutic bacteria to anchor within the intestinal lining for multiple days, promoting sustained release of the drug from the biofilm coating.  

“This will generate a significant impact in either academia or industry fields because it has the potential to decrease the dosing of the drug and potentially enhance the treatment efficacy,” said Quanyin Hu, a pharmaceutical scientist at the University of Wisconsin-Madison who was not involved with the study.  “It will provide an inspiration for how to take advantage of the natural delivery system to enhance the drug delivery efficacy.”

Choudhury’s team tested the bacterioboat system’s drug-delivery capabilities in a tumor-bearing mouse model. Plasma concentrations of the orally delivered anticancer drug 5-FU peaked at three hours and were no longer detectable eight hours after administration. However, 5-FU delivered by bacterioboat persisted in circulation for up to 24 hours. 

Mice that received a standard orally-delivered drug and those that received a half-dose of the bacterioboat delivered drug showed equivalent reductions in their tumors, demonstrating that bacterioboat allows for smaller drug quantities to produce a clinically significant effect. In a measurement of side effects, the half-dose of bacterioboat caused no liver toxicity, while the full dose of the conventionally-delivered drug caused some liver capillary destruction. 

Choudhury is optimistic that this drug delivery system may one day be widely used for drugs that are insoluble or have low permeability . “It has huge potential because this particular system doesn’t require you to change the chemistry of the drug,” Choudhury said. “It can actually increase the potency of any drug.”

References

1. Kondamudi, P.K. et al. Drugs as causative agents and therapeutic agents in inflammatory bowel disease. Acta Pharm Sin B  3, 289-296 (2013).
2. Kaur, P. et al. Bacterioboat—A novel tool to increase the half-life period of the orally administered drug. Sci Adv  8, eabh1419 (2022).