The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed.

No abstract

The development of effective forms to incorporate poorly soluble drugs into delivery systems remains a problem. Thus, it is important to find alternatives such as finding excipients that increase drug solubility. Ionic liquids (ILs), particularly choline-based ILs, have been studied as solubility enhancers in drug delivery systems. Nonetheless, to acknowledge this property as a functionality, it needs to be proven at non-toxic concentrations. Hence, herein two choline-amino acid ILs were studied as functional excipients by evaluating their influence on the solubility of the poorly water-soluble ferulic acid and rutin, while considering their safety. The solubility of the drugs was always higher in the presence of the ILs than in water. Ionic liquids did not affect the radical scavenging activity of the drugs or the cell viability. Moreover, stable oil-in-water (O/W) emulsions were prepared containing each drug and the ILs, allowing a significantly higher drug loading. Globally, our results suggest that choline-based ILs may act as green functional excipients, since at non-toxic concentrations they considerably improve drug solubility/loading, without influencing the antioxidant activity of the drugs, the cell viability, or the stability of the formulations.

The renal cell carcinoma (RCC) is the most common type of kidney cancer. Identifying novel and more effective therapies, while minimizing toxicity, continues to be fundamental in curtailing RCC. Rutin, a bioflavonoid widely found in nature, has shown promising anticancer properties, but with limited applicability due to its poor water solubility and pharmacokinetics. Thus, the potential anticancer effects of rutin toward a human renal cancer cell line (786-O), while considering its safety in Vero kidney cells, was assessed, as well as the applicability of ionic liquids (ILs) to improve drug delivery. Rutin (up to 50 µM) did not show relevant cytotoxic effects in Vero cells. However, in 786-O cells, a significant decrease in cell viability was already observed at 50 µM. Moreover, exposure to rutin caused a significant increase in the sub-G1 population of 786-O cells, reinforcing the possible anticancer activity of this biomolecule. Two choline-amino acid ILs, at non-toxic concentrations, enhanced rutin’s solubility/loading while allowing the maintenance of rutin’s anticancer effects. Globally, our findings suggest that rutin may have a beneficial impact against RCC and that its combination with ILs ensures that this poorly soluble drug is successfully incorporated into ILs–nanoparticles hybrid systems, allowing controlled drug delivery.