A preliminary investigation into the activity and toxicity of an amyloid-based Emodin formulation

Emodin is a natural plant derivative with many therapeutic properties including anti-cancer, anti-apoptosis, and anti-inflammatory effects. However, the delivery of Emodin is quite challenging due to its superhydrophobic properties. Furthermore, conventional systemic delivery approaches often result in side effects. Thus, alternative strategies are important for the successful delivery of Emodin. The goal of this study was to develop a novel Emodin drug depot utilizing peptide amyloids. For the peptides, an aggregation-prone amino acid domain of receptor-interacting serine/threonine-protein kinase 3 (RIP3) protein was used. The RIP3/Emodin amyloid aggregates physicochemical characterization, cellular uptake, effects on toxicity, oxidative stress, and inflammation were investigated. Studies reveal that Emodin-encapsulated RIP3 peptide amyloid aggregates were able to induce significant lung cancer cell toxicity compared to free Emodin. Further, aggregates alone did not exhibit toxicity and or oxidative stress. In addition, the formulation was able to inhibit lipopolysaccharide (LPS) mediated inflammation in macrophage cells. Overall, the studies indicate the potential of RIP3 peptide amyloids as hydrophobic drug depots.