Tunable jelly takes ups and downs out of peptide delivery

A tunable jellylike depot could extend the half-life of peptide drugs, allowing delivery without the peaks and valleys often associated with these drugs.

Peptide drugs are rapidly cleared from the bloodstream, so they have to be dosed frequently. This has two downsides: the inconvenience and pain of regular injections and the side effects linked with varying drug levels in the blood. To get around these issues, a team of biomedical engineers from Duke University has created protease-operated depots (PODs). These are genetically engineered fusion proteins that link multiple copies of a peptide drug to an elastin-like polypeptide. The protein is liquid at room temperature but sets into a jelly under the skin, where it is broken down by naturally occurring proteases, releasing the drug at a controlled and preprogrammed rate.

"We wanted to know if we could create a system that does what the polymer microspheres do, but gets rid of the microspheres and is more patient-friendly," said Ashutosh Chilkoti, a professor of biomedical engineering at Duke's Pratt School of Engineering.

To prove the concept, the researchers engineered E. coli bacteria with a synthetic gene construct to produce a fusion protein that combined the Type 2 diabetes therapeutic glucagonlike peptide-1 (GLP-1) and the heat-sensitive polymer. A single injection of the protein reduced blood glucose in mice up to 5 days, about 120 times longer than the peptide alone.

"This new delivery system provides the first entirely genetically encoded alternative to peptide drug encapsulation for sustained delivery of peptide drugs," Chilkoti said.

While there are a number of companies developing oral and injectable peptide delivery systems, there is a big potential market for these, as there are more than 40 peptide drugs approved for use in humans, including insulin, and more than 650 currently in clinical trials.

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