Nanostructured archaeolipid carriers for the treatment of inflammatory bowel diseases

HIGA LH; SCHILRREFF P; JEREZ HE; ROMERO EL; MORILLA MJ

Mar del Plata

Congreso; SAIC.SAI.SAFIS 2018; 2018

Inflammatory bowel diseases (IBD) are chronic relapsing disorders of the gastrointestinal tract, charac¬terized by chronic inflammation and epithelial injury induced by the uncontrolled activation of the mucosal immune system. Dendritic cells and macrophages are key cells in the inflamed mucosa, which produce large amounts of pro-inflammatory cytokines. Overproduction of reactive oxygen species (ROS) is also involved in symptoms of IBD.Herein, we have prepared nanostructured archaeolipid carriers (NAC) composed by a core of neutral archaeal lipids (NA) as antioxidants and a shell of polar archaeolipids (PA) as hydrolytic, oxidative, and enzymatic attack resistant lipids and carrying dexamethasone (D-NAC) for oral delivery. The anti-inflammatory and anti-oxidant activities of D-NAC submitted to in vitro digestion were evaluated in a co-culture model of inflamed intestine consisting of human intestinal cell monolayers, Caco-2 cells, and human monocyte-derived macrophages THP-1 cells, stimulated with lipopolysaccharide (LPS) and compared with carriers without archaeal lipids (D-NLC).D-NAC made of a core of a compritol and NA containing dexamethasone and stabilized by a shell of PA and Tween 80 (2; 2; 1.2; 3% w/w) were prepared by homogenization-ultrasonication. D-NAC showed mean size of 60 ± 9 nm and zeta potential of -32 ± 5 mV and no changes in mean size was observed after in vitro digestion. Lipolysis of NLC was relatively fast, being almost completely digested in 30 minutes. In contrast, the lipolysis was significative lower for NAC, up to 60 min the accumulative lipolytic percentage was only 25%. Digested D-NAC decreased the secretion of TNF-α and IL-8 and showed higher antioxidant activity than digested D-NLC in the co-culture model.Thus, the ultra-small, highly negatively charge D-NAC resulted highly stable under gastrointestinal conditions, reduced the secretion of the pro-inflammatory cytokines, and showed high antioxidant activity. These D-NAC could be the most promising candidate for IBD treatments.