UCLA researchers from the Department of Medicine-Endocrinology have formulated a novel nanoparticle for management of hypoglycemia that can efficiently deliver glucagon, while also allowing for long-term stabilization and storage.
BACKGROUND: Hypoglycemia is a condition characterized by abnormally low blood glucose levels, posing a significant risk for individuals with type 1 diabetes. Glucagon (GCG) has been integral to managing hypoglycemia by promoting glycogen breakdown in the liver, thus increasing blood glucose levels. Despite its importance, GCG is unstable in aqueous solutions, presenting challenges for developing therapeutics. Recent innovations such as Eli Lilly’s BAQSIMI® nasal GCG offer a more user-friendly administration option, but they are only stable between 25-30 °C. To overcome this issue, an aqueous GCG formulation, ZEGALOGUETM, was developed, but it has a maximum storage temperature of 25 °C for up to 12 months. Therefore, there is a demand to create therapeutics that enable long-term stabilization and storage of GCG to treat hypoglycemia.
INNOVATION: UCLA researchers have developed a novel formulation for the delivery of GCG that effectively increases blood glucose levels, while also allowing for long-term stabilization and storage. Researchers synthesized poly(trehalose) diblock copolymer nanoparticles with complex morphologies and confirmed, using transmission electron microscopy and dynamic light scattering, that their structure and size remained intact after exposure to aqueous media. The nanoparticles were exposed to thermal stress and analyzed by high-performance liquid chromatography, which confirmed their stability at elevated temperatures. UCLA researchers also performed in vivo mouse studies to evaluate the efficacy of GCG-nanoparticle conjugates in mice with hypoglycemia and found that delivery of the GCG-coated vesicles (i) restored glucose levels, and (ii) induced a more pronounced and sustained elevation of blood glucose compared to other formulations. After assessing the stability of GCG-vesicle conjugates in various conditions, researchers found that the GCG nanoparticles retained their biological activity even after 30 days of storage at room-temperature. In summary, UCLA researchers have developed a novel nanoparticle capable of delivering GCG while maintaining stability under room temperature and extended storage conditions. This finding provides potential for GCG delivery in hypoglycemia management, especially in contexts where room-temperature stability in aqueous solution is critical.
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ADVANTAGES:
DEVELOPMENT-TO-DATE: UCLA researchers have developed a novel poly(trehalose) diblock copolymer nanoparticle to deliver GCG which has been validated in in vitro and in vivo contexts.
KEYWORDS: Nanoparticle, glucagon, Trehalose Diblock Copolymers, hypoglycemia, type 1 diabetes, glycogen, vesicles, transmission electron microscopy, dynamic light scattering, high-performance liquid chromatography