NOVEL NANOVESICLES INCREASED STABILITY AND ANTIOXIDANT ACTIVITY OF SUPEROXIDE DISMUTASE

SCHILRREFF, P; SIMIONI, Y; ROMERO, EL; MORILLA, MJ

Congreso; LXIII Reunión científica anual de la Sociedad Argentina de Investigación Clínica SAIC; 2018

Inflammatory bowel diseases (IBD), such as Crohn?s disease or colitis are associated with an imbalance, comprising increased reactive oxygen species (ROS) and decreased antioxidant activity. Antioxidant enzymes, such as superoxide dismutase (SOD), play a key role in diminishing oxidative stress and has attracted considerable attention on treatment of ROS-related disorders. However, clinical applications of SOD are very limited due to its instability. On the other hand, we have previously demonstrated that nanovesicles prepared with archaeolipids (ARC) have greater resistance to hydrolytic attacks, oxidation and lipolysis, unlike vesicles prepared with phospholipids named liposomes (LIPO). Therefore, we propose ARC as a useful oral delivery system for SOD that can provide protection to proteolysis during the gastrointestinal transit. ARC loaded with SOD (ARC-SOD) were prepared by thin-film hydration followed by extrusion method. Nano-sized (240 ± 8.9 nm), monodisperse (polydispersity index, PdI: 0.237 ± 0.02) and negative Z-potential (-34.34 ± 1.39 mV) were obtained. Colloidal stability of ARC-SOD was measured during storage and after simulated digestion process. Antioxidant and anti-inflammatory activity on macrophages stimulated with H2O2 or lipopolysaccharides (LPS) for both digested and undigested vesicles, was determined by MTT assay and measuring the levels of proinflammatory cytokines, respectively. Intracellular ROS levels were identified using flow cytometry. Effectiveness of the ARC-SOD was compared with LIPO-SOD. ARC-SOD reduced the levels of IL-6 and TNF-α and ROS production on macrophages stimulated LPS as compared with free SOD or loaded in ordinary LIPO. After in vitro digestion, size, PdI and the antioxidant activity of ARC-SOD was retained, while that of LIPO-SOD was lost. In conclusion, ARC-SOD conferred SOD with better stability and enhanced therapeutic potential, offering a promising oral delivery option in treatment of IBD.