A new slow-release jelly delivery system has been developed at Duke University that overcomes the shortcomings of a promising class of peptide drugs known as very small proteins, which are typically used to treat diabetes and cancer.
The new approach involves making a ‘fusion protein’ with multiple copies of a peptide drug attached to a polymer that is sensitive to body heat. In this way, the fusion molecule is engineered to be in liquid form when in a syringe, but turns into jelly when injected under the skin.
Natural enzymes present in the skin then attack the injected drug and release the peptide in a constant, controllable amount over time.
More than 40 peptide drugs have been approved for use in humans and more than 650 are currently being tested. One instance is the hormone insulin, a peptide that controls carbohydrate metabolism and typically used to treat diabetes.
However, peptide drugs can’t presently achieve their full potential because they are rapidly degraded and cleared from the body. This means they have to be given as multiple, frequent injections which can be very uncomfortable and painful.
This also creates many unwanted health problems for patients because peptide concentrations in blood rise sharply just after injection and fall just as sharply soon afterwards.
In these latest experiments, researchers fused glucagon-like peptide-1 (GLP-1) - a hormone that regulates insulin release - with a genetically engineered heat-sensitive polymer to create a delivery system known as a protease-operated depot or POD.
A single injection of GLP-1 POD reduced blood glucose levels in mice for up to five days, which is 120 times longer than an injection of the peptide alone.
For a patient with type 2 diabetes, it’s obviously much more desirable to be able to inject a drug once a week or month rather than once or twice a day. Not only that, such an approach avoids the problematic peaks and valleys of drug concentrations seen with normal injections.
PODs are also relatively easy to make because both the peptide drug and the heat-sensitive polymer are made of amino acids, which can be made as one long stretch by specially engineered bacteria.
In short - this exciting new approach promises to be the first genetically encoded delivery system for peptide drugs and is likely to unleash their full potential, making them highly effective in treating disease.