A promising drug delivery method that could replace injectables with drugs

For chronic conditions like rheumatoid arthritis, treatment often requires lifelong injections of medication. Fear of needles, infection from injections, and pain are factors that cause patients to miss doses, which encourages the development of new infusion strategies that combine efficacy with limited side effects to adequately treat patients.

Researchers at Baylor College of Medicine and collaborating institutions have discovered a better way to deliver drugs that don’t require an injection but can be as easy as swallowing a pill. Research appears in Proceedings of the National Academy of Sciences.

“People don’t want injections for the rest of their lives,” said Dr. Christine Beeton, professor of integrative physiology at Baylor. “In our current work, we explored the possibility of using biological bacteria Lactobacillus reuteri as a novel oral drug delivery platform for the treatment of rheumatoid arthritis in animal models.”

Previous work from the Beeton laboratory has shown that a peptide (short protein) derived from anemone toxin effectively and safely reduces disease severity in a mouse model of rheumatoid arthritis. low and patients with plaque psoriasis. “However, peptide treatment requires repeated injections, reduces patient compliance, and direct oral delivery of peptides has low efficacy,” says Beeton.

Beeton collaborated with Dr. Robert A. Britton, professor of microbiology and molecular virology and a member of the Dan L Duncan Comprehensive Cancer Center at Baylor. Britton Laboratories has developed the tools and expertise to transform probiotics bacteria for the production and release of compounds. In the present study, the team bioprocessed the probiotic L. reuteri to secrete the ShK-235 peptide derived from anemone toxin.

They chose L. reuteri because these bacteria are native to the intestines of humans and other animals. This is one of a group of lactic acid bacteria that have long been used as a cell factory in the food industry and are recognized as safe by the US Food and Drug Administration. L. reuteri has an excellent safety profile in infants, children, adults, and even in immunosuppressed populations.

“The results are encouraging,” Beeton said. “Daily administration of these peptide-secreting bacteria, known as LrS235, significantly reduced clinical signs of the disease, including arthritis, cartilage destruction, and bone damage in animal models. rheumatoid arthritis.”

The researchers monitored the bacterium LrS235 and the peptide ShK-235 it secretes inside animal models. They found that after feeding mice with live LrS235 releasing ShK-235, they were able to detect ShK-235 in the blood circulation.

“Another reason we chose L. reuteri is that these bacteria don’t stay permanently in the gut,” says Beeton. “They are eliminated as the gut regularly renews the inner surface layer on which the bacteria attach.” . “This opens up the possibility of tailoring treatment management.”

More research is needed to bring this new drug delivery system into the clinic, but the researchers predict that it could make treatment easier for patients in the future. “These bacteria can be stored in capsules that can be left on the kitchen counter,” says Beeton. “A patient can take the capsule while on vacation without refrigeration or carrying a needle and continue treatment without the inconvenience of daily injections.”

These findings provide an alternative delivery strategy for peptide-based drugs and suggest that such techniques and principles could be applied to a wider range of drugs and the treatment of chronic inflammatory diseases .

Other contributors to this work include Yuqing Wang, Duolong Zhu, Laura C. Ortiz-Velez, Jacob L. Perry, Michael W. Pennington and Joseph M. Hyser.