Biomedical engineers have developed a novel delivery method for a new class of drugs called peptide drugs – these very small proteins that can help regulate metabolism and treat diabetes.
But peptide drugs rapidly degrade in the bloodstream, and their rapid clearance from the body means multiple, frequent injections. Because of this, their concentrations in the blood spike right after injection then fall dramatically, causing unwanted side effects.
To overcome these hurdles, a team led by Ashutosh Chilkoti of Duke University came up with a new delivery system they’re calling POD, for protease-operated depot:
- Multiple copies of a peptide drug are fused to a polymer, which creates a ‘fusion protein.’
- The molecule, which is sensitive to body heat, is a liquid in a syringe; it transforms into a jelly when injected under the skin.
- Enzymes in the skin attack the POD, freeing up the copies of the peptide, which go on to provide a constant and controllable release of drug over time.
To test the method, the team fused glucagon-like peptide-1 (GLP-1), a hormone that regulates the release of insulin, with a genetically engineered heat sensitive polymer to create the POD.
A single injection of the GLP-1 POD reduced blood glucose levels in mice for up to five days -- that’s 120 times longer than an injection of the peptide alone. “For a patient with type 2 diabetes, it would be much more desirable to inject such a drug once a week or once a month rather than once or twice a day,” Chilkoti says.
More than 40 peptide drugs are approved for human use and more than 650 are being tested in clinical studies.
The work was published in the Proceedings of the National Academy of Science last week.
[Via Duke University]
Image by Jill A. Brown via Flickr