Snakebite envenomation affects millions of people annually, with current treatments limited to animal-derived antivenoms. Repurposed drug inhibitors of toxin families offer an exploitable opportunity to improve snakebite treatment, including heparins that can inhibit chemotherapy with withdrawals. However, to be effective therapies in the field, such treatments must be engineered into drug delivery devices capable of rapidly administering drug(s) to the site of intoxication. Here we introduce the concept of integrating heparins, specifically unfractionated heparin (H) and its low-molecular-weight heparinoid variant, tinzaparin (T), into hydrogels composed of whey protein isolate (WPI), an inexpensive by-product of the dairy industry that is cytocompatible, rigid, autoclavable, and has the local release function. dressings. The aim of this research was to investigate whether heparin-containing WPI hydrogels showed physical properties suitable for wound dressings and could effectively release drugs in sufficient quantities to inhibit the cytotoxic activity of spitting cobra venom. To do this, five hydrogel prototypes were produced: 40% WPI no drug control, and 5% H, 10% H, 5% T, and 10% T, all within 40% WPI hydrogels. It was determined that heparins successfully incorporated into WPI hydrogels and heparin-containing WPI hydrogels showed improved swelling compared to 40% WPI no drug control, suggesting improved absorption of wound exudate; However, this heparin integration also increased the hydrogel degradation rate in simulated wound environments. Most importantly, sufficiently high concentrations of T were released into phosphate-buffered saline from the 10% T hydrogels to neutralize Naja nigricollis venom cytotoxicity in a HaCaT cell cytotoxicity model. Together, our results suggest that the integration and diffusion of anti-venom drugs in WPI hydrogels is possible, and that the development of such drug-integrated hydrogels for snakebite wound dressings requires further research.
