“Jelly” Drugs for Better Delivery
(Ivanhoe Newswire) – More than 40 peptide drugs are approved and more than 650 are being testing in clinical studies for treating diseases such as diabetes and cancer. Researchers at Duke University have developed a new delivery system that overcomes the peptide drugs’ shortcomings.
Peptide drugs are very small proteins. An example is the hormone insulin. It is a peptide that regulates the metabolism of carbohydrates in the body and is used as a drug to treat diabetes.
Peptide drugs are mostly effective, but they cannot achieve their full potential. They are rapidly degraded in the blood stream and are cleared from the body, which will result in multiple, frequent injections. This will cause peptide concentrations in the blood to rise after injection and fall dramatically soon after, resulting in unwanted side effects for the patient.
A popular method to solve this problem involves loading peptide drugs into polymer microspheres that are injected under the skin and slowly degrade to release the peptide drugs. This technology has been proven useful, but has issues related to manufacturing.
"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," Ashutosh Chilkoti, Theo Pilkington professor of biomedical engineering in Duke’s Pratt School of Engineering, was quoted as saying.
The new approach will involve making a “fusion protein,” which has multiple copies of a peptide drug fused to a polymer that is sensitive to body heat. The fusion molecule is a liquid, but transforms into a “jelly” when it is injected underneath the skin. Enzymes will begin to attack the drug and liberate copies of the peptide, providing a constant and controlled release of the drug.
Former graduate student and first author, Miriam Amiram said the new delivery system should be for protease-operated depot (POD). In the latest experiments, researchers fused glucagon-like peptide-1 (GLP-1), a regulating hormone, with a genetically engineered heat-sensitive polymer to create the POD.
"Remarkably, a single injection of the GLP-1 POD was able to reduce 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 would be much more desirable to inject such a drug once a week or once a month rather than once or twice a day.
Additionally, this approach avoids the peaks and valleys of drug concentrations that these patients often experience. This new delivery system provides the first entirely genetically encoded alternative to peptide drug encapsulation for sustained delivery of peptide drugs," Chilkoti concluded.
SOURCE: Journal Proceedings of the National Academy of Sciences, January 2013