New research-Improving GLP-1 drug delivery by 'painting' it on antibodies

Pentelute and his team have developed a technology to attach GLP-1 receptor agonists to IgGs within the body. The drug delivery system, which he calls in vivo antibody painting, is itself a peptide and is composed of a binder region that attaches to the IgG, a payload region that carries the GLP-1 receptor agonist, and a reactive region that attaches (i.e., paints) the GLP-1 drug onto the IgG with a covalent bond.

In laboratory tests of the antibody painting platform on mouse and human IgGs, the researchers found that nearly half of all antibodies successfully attached to GLP-1 receptor agonists at a body temperature of 98.6 degrees Fahrenheit (37 degrees Celsius).

Next, they tested the platform for delivering GLP-1 receptor agonists in a mouse model for Type 2 diabetes and metabolic-induced obesity. Pentelute and his colleagues found that the mice experienced sustained blood glucose management and weight loss for up to 15 days after a single treatment. In fact, mice that received antibody painting had better and longer lasting results at a GLP-1 drug dose much lower than the current traditionally administered dose.

The researchers have shared their findings in a preprint research article that is currently under peer review. Pentelute will expand upon this work during his ACS Spring 2025 presentation, including new results from demonstrations showing that the platform can effectively paint antibodies in the presence of extracellular debris such as cellular proteins.

“We’re also expanding the technology to make antibody drug conjugates for cancer,” shares Pentelute. “And we’re modifying this technology to be able to paint multiple drugs onto one antibody,” he adds. “With new technology like this, the future of peptide-based therapies could see reduced costs and enhanced effectiveness.”

Reference:

Improving GLP-1 drug delivery by ‘painting’ it on antibodies, American Chemical Society, Meeting: ACS Spring 2025.