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Biopolymer Injection Offers Long-Term Glucose Control

By HospiMedica International staff writers
Posted on 19 Jun 2017
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Image: An injection every fortnight could help control type 2 diabetes (Photo courtesy of ShutterStock).
Image: An injection every fortnight could help control type 2 diabetes (Photo courtesy of ShutterStock).
A novel biopolymer injection with an optimized glucagon-like peptide-1 (GLP1) formulation could potentially replace daily insulin shots with one administered just once or twice a month.

Under development at Duke University (Durham NC, USA) and PhaseBio Pharmaceuticals (Malvern, PA, USA), the new approach fuses GLP1 with a heat-sensitive biopolymer called elastin-like polypeptide. Held in a solution, the biopolymer drug can be injected into the body, forming a subcutaneous depot. Once it enters the bloodstream, body heat causes it to convert into a biodegradable gel that releases the drug slowly and steadily, without the characteristic short half-life of the native ligand that results from enzymatic inactivation and rapid clearance.

The researchers conducted animal studies that showed that a single injection of GLP1 resulted in zero-order release kinetics and circulation times of up to 10 days in mice and 17 days in monkeys. The optimized pharmacokinetics lead to 10 days of glycemic control in three different mouse models of diabetes, as well as the reduction of glycosylated hemoglobin (A1c) levels and weight gain in obese mice treated once weekly for eight weeks. The researchers added that the design principles could also improve the pharmacological performance of other peptide and protein therapeutics. The study was published on June 5, 2017, in Nature Biomedical Engineering.

“What's exciting about this work was our ability to demonstrate that the drug could last over two weeks in non-human primates,” said lead author Kelli Luginbuhl, MSc, a PhD student at Duke University. “Because our metabolism is slower than monkeys and mice, the treatment should theoretically last even longer in humans, so our hope is that this will be the first bi-weekly or once-a-month formulation for people with type 2 diabetes.”

GLP-1 is a peptide hormone that can decrease blood sugar levels in a glucose-dependent manner by enhancing the secretion of insulin. Endogenous GLP-1 is rapidly degraded by dipeptidyl peptidase-4 (DPP-4), neutral endopeptidase 24.11, and renal clearance, resulting in a half-life of approximately two minutes; consequently, only 10-15 % of GLP-1 reaches circulation intact. To overcome this, GLP-1 receptor agonists and DPP-4 inhibitors have been developed to resist and reduce this activity. GLP-1-based treatment has also been associated with weight loss and lower hypoglycemia risks.

Related Links:
Duke University
PhaseBio Pharmaceuticals

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