Ozoile-alginate microspheres for the therapeutic management of Crohn's disease

Ozone is a highly unstable gas with strong oxidizing capacity that can be successfully applied for medical treatments. The ozone effects on wounds healing and tissues repairing have been widely studied, whereas its oxidizing capacity has been tested in order to verify its disinfectant and sanitizing properties. Ozone reacts with the olephinic bonds of olive oil forming the ozonides, a class of chemical compounds that represent an alternative to drug therapy due to their features. In this work, we used stable ozonides (Ozoile®) produced in a patented process. Ozoile® releases molecular oxygen driving the production of radical species with the generation of moderate oxidative stress in the environments characterized by a protonic increase, such as ischemic, hypoxic, or damaged tissues. Moderate oxidative stress stimulates the expression of numerous antioxidant enzymes by the activation of the nuclear factor-erythroid 2-related factor 2 (Nrf2). The generation of a moderate pro-oxidant environment leads to the stimulation of molecular mechanisms that are able to suppress the inflammatory response. Moreover, the oxidative stress may induce the expression of the hypoxia-inducible factor-1α (HIF-1α), which is a transcription factor mainly associated to the adaptive responses of cells to hypoxia. HIF-1α induces the expression of hundreds of genes, among these there are several growth factors such as vascular endothelial growth factor (VEGF), platelet- derived growth factor (PDGF), fibroblast growth factor (FGF), transforming growth factor-α (TGF-α), and TGF- β, which are involved in the complex multi-step process of tissue regeneration. In this work, Ozoile® was embedded into stimuli-responsive sodium alginate microspheres (SRAMs) with the aim to reach targeted inflammatory sites (Figure 1). In this perspective, Ozoile-SRAMs represent a new and smart technology for drug delivery in the therapeutic management of Crohn’s disease (CD), which is a chronic inflammatory bowel pathology mainly affecting the ileum and colon. This disease is characterised by intestinal ulcers that can cause stenosis or fistulas. Here, the Ozoile-SRAMs could be effective releasing the active ozonide principle thus favouring the healing.