Problem statement: To date, insulin is the most accepted therapeutic solution available for controlling
hyperglycemia. The treatment for diabetes has improved over the years from syringes for injecting insulin to
insulin pens to pumps and sensor-augmented implantable devices trying to improve patient care. However,
the accuracy, requirement of skilled personnel, lack of social acceptance, and inconvenience to the user are
some of the factors that make diabetes treatment unpopular and detested. Continuous effort is
required to improve the treatment and patient experience. In this regard, the developed amyloid delivery depot will aid in the precise delivery of active insulin with minimal invasiveness, immune response, and long-term controlled and sustained release of insulin for treating hyperglycemia. Hence, eliminating the need for frequent injections during treatment and providing a better patient experience.
Project details: Hydrogels are hydrophilic (water-loving) 3D networks formed by polymers. Due to the
hydrophilic property of the polymers present in the network, they can absorb water and swell. This property
can be utilized in many applications such as tissue engineering, support structure for cells, etc. Amyloid
hydrogels are hydrogels that are formed by the 3D network of protein fibrils. They have a multitude of
applications in various biomedical and bio-nanotechnological fields. Globally, various studies are going on to
explore delivery systems of chemical and biological origin for releasing insulin for the treatment of diabetes.
Most of them fail to provide long-term controlled insulin release. While some studies show immune
reactions some other methods require sophisticated methods for preparation, preservation, and storage. So,
there is an unmet demand for a non-toxic method for the long-term release of insulin.
We propose to use non-toxic functional amyloid-based hydrogels as depots for releasing biologically active
insulin. This system can protect the biological, physical, and chemical integrity of the drug molecule in the
stable cross-β-sheet (3D network) structure without any chemical cross-linking during processing, storage,
and delivery. Additionally, thixotropicity (the property of becoming less viscous when subjected to applied
stress) of the formulation enables easy subcutaneous administration where the released insulin can be
carried over to the main blood vessels through capillaries. Our previous study showed that the designed
amyloid hydrogels can release insulin in a controlled and sustained manner in vitro. We confirmed that the insulin released from the hydrogels was biologically active and can reduce the blood glucose level upon
administration. The specific aims of the project include evaluating the insulin release efficacy of designed functional amyloid hydrogels in vivo (diabetic animal model), modulating the mechanical and physio-chemical properties of the selected hydrogel by incorporating bio-adhesives, enhancing the effectiveness of the hydrogel by co-
encapsulating insulin with amylin analog and assessing the long-term toxicology effect of the developed formulation using animal models.