Nanostructured archaeolipid carriers for the treatment of inflammatory bowel diseases"

LETICIA H HIGA; PRISCILA SCHILRREFF; ANDRES BRISKI; HORACIO JEREZ; EDER ROMERO; MARIA JOSE MORILLA

Mar del Plata

Congreso; Reunion Anual SAIC NanomedAR 2018; 2018

SAIC NANOMED

Inflammatory bowel diseases (IBD) are chronic relapsing disordersof the gastrointestinal tract, charac¬terized by chronic inflammation and epithelial injury induced by the uncontrolled activation ofthe mucosal immune system. Dendritic cells and macrophages arekey cells in the inflamed mucosa, which produce large amounts ofpro-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 ofinflamed intestine consisting of human intestinal cell monolayers,Caco-2 cells, and human monocyte-derived macrophages THP-1cells, stimulated with lipopolysaccharide (LPS) and compared withcarriers 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-NACshowed mean size of 60 ± 9 nm and zeta potential of -32 ± 5 mVand 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 forNAC, up to 60 min the accumulative lipolytic percentage was only25%. Digested D-NAC decreased the secretion of TNF-α and IL-8and showed higher antioxidant activity than digested D-NLC in theco-culture model.Thus, the ultra-small, highly negatively charge D-NAC resulted highly stable under gastrointestinal conditions, reduced the secretion ofthe pro-inflammatory cytokines, and showed high antioxidant activity. These D-NAC could be the most promising candidate for IBDtreatments.