Bacterioruberin from Haloarchaea plus dexamethasone in ultra-small macrophage-targeted nanoparticles as potential intestinal repairing agent

HIGA, LETICIA HERMINIA; SCHILRREFF, PRISCILA; BRISKI, ANDRÉS MARTÍN; JEREZ, HORACIO EMANUEL; DE FARIAS, MARCELO ALEXANDRE; VILLARES PORTUGAL, RODRIGO; ROMERO, EDER LILIA; MORILLA, MARIA JOSE

COLLOIDS AND SURFACES B-BIOINTERFACES

ELSEVIER SCIENCE BV

Año: 2020 vol. 191

0927-7765

Oral administration of antioxidant and anti-inflammatory drugs have the potential to improve thecurrent therapy of inflammatory bowel disease. Success of oral treatments, however, depends onthe capacity of drugs to remain structurally stable along the gastrointestinal tract, and on thefeasibility of accessing the target cells. Delivering anti-inflammatory and antioxidant drugs tomacrophages using targeted nanoparticles, could make treatments more efficient. In this workstructural features and in vitro activity of macrophage-targeted nanostructured archaeolipidcarriers (NAC) containing the high antioxidant dipolar C50 carotenoid bacterioruberin (BR) plusdexamethasone (Dex): NAC-Dex, are described. Ultra-small (66 nm), -32 mV  potential, 1200g Dex /ml NAC-Dex, consisted of a compritol and BR core, covered by a shell of sn 2,3 etherlinked archaeolipids and Tween 80 (2: 2: 1.2: 3 % w/w) were obtained. NAC-Dex were extensivelycaptured by macrophages and Caco-2 cells and displayed high anti-inflammatory and antioxidantactivities on a gut inflammation model made of Caco-2 cells and lipopolysaccharide stimulatedTHP-1 derived macrophages reducing 65 % and 55 % TNF- and IL-8 release, respectively and60 % reactive oxygen species production. NAC-Dex also reversed the morphological changesinduced by inflammation and increased the transepithelial electrical resistance, partlyreconstituting the barrier function. Activity of BR and Dex in NAC-Dex was partially protected aftersimulated gastrointestinal digestion, improving the chances of BR-Dex joint activity. Resultssuggest that oral NAC-Dex deserve further exploration as intestinal barrier repairing agent