Unmet NeedType 2 diabetes (T2D) contributes to 90% of all cases of diabetes and represents a critical global public health problem. T2D specifically affects glucose metabolism and those with the disease either do not produce enough insulin or do not respond properly to insulin signaling to maintain normal levels of glucose in the blood. Several serious complications can result from T2D and only maintenance therapy exists. The most effective drug therapy for T2D is glucagon-like peptide-1 (GLP-1), but its short half-life in the blood of less than 2 minutes represents a critical challenge for actual clinical application. At present, there have been many attempts to generate analogs of GLP-1 that have better circulation and longer half-lives. One especially promising candidate is exendin-4, which has a 20-30 time longer blood half-life, shares 53% sequence homology to GLP-1, and demonstrates many necessary glucoregulatory functions. However one potential caveat to the use of exendin-4 is that it has poor serum stability, requiring injection twice daily. Consequently, there is a critical unmet need to enhance the durability and effectiveness of exendin-4 treatment as well as its serum stability and circulation time for improved treatment of T2D that results in fewer injections and better overall patient compliance.
Technology OverviewJohns Hopkins researchers developed a tannic acid (TA)/exendin-4/Fe
3+ ternary nanoparticle system that complexes TA and exendin-4 stabilized via a TA-Fe
3+ coordination. These nanoparticles were highly uniform and had a high encapsulation efficiency of exendin-4. The system enables the nanoparticles to release their encapsulated peptides in a pH-dependent and controlled manner. Upon IP injection of the exendin-4 nanoparticles into a T2D mouse model, they achieved a rapid reduction in blood glucose levels in less than 12 hours. They were able to maintain normal levels for 72 hours and levels were maintained below the therapeutic threshold for 6 days with only one injection. The exendin-4 nanoparticles also had better blood circulation time and half-life compared to protein alone. This TA/exendin-4/Fe
3+ ternary nanoparticle system represents a potential novel treatment method for T2D but could be scalable to other peptides and disease systems.
Stage of DevelopmentThe inventors have developed a method for the scalable production of a nanoparticle system that can be used to encapsulate bioactive proteins with high efficiency and a controllable release rate. This system of peptide-loaded nanoparticles has the potential to treat a variety of diseases. Thus far, it has been tested for T2D in mice but further research and optimization is required to expand the system to other diseases and ultimately human patients.
PublicationsHe Z, et al. Journal of Controlled Release 301, 119-128, 2019