Nanoparticle lipid carriers decorated with archaeal lipids for targeting to macrophages

HIGA, LETICIA; JEREZ, HORACIO; BRISKI, ANDRES; ROMERO, EDER L; MORILLA, MARIA J.

Mar del Plata

Congreso; SAIC-SAI-SAFE 2016; 2016

Inflammatory bowel diseases (IBD) such as Crohn?s disease and ulcerative colitis are disorders of the gastrointestinal tract, characterized by chronic inflammation and epithelial injury induced by the uncontrolled activation of the mucosal immune system. We hypothesize safer therapies could rely on developing macrophages-targeted drug delivery systems capable of specifically delivering high doses of anti-inflammatory and anti-oxidant drugs with minimal exposure of healthy or distant tissues via oral administration.In the present work, we developed nanostructured lipid carriers (NLC) made of a core composed of a mixture of solid (compritol) and liquid (neutral archaeal) lipids stabilized by a shell of polar archaeal lipids and Tween 80, containing dexamethasone. Neutral and polar archaeal lipids of the hyperhalophile archaea Halorubrum tebenquichense provided the nanoparticles with anti-oxidant activity, stability under gastrointestinal conditions and the advantage to be uptaken by macrophages via scavenger receptor class A, respectively. NLC of 100 -300 nm, Z-potential from -38 to -50 mV, entrapment efficiency of 37%, were stable over 31 days of storage at 4°C. DSC showed a decrease of melting point of compritol and low recrystallinity index, indicating the liquid lipid was dispersed within the compritol matrix.TEM micrographs showed spherical shape nanoparticles. No cytotoxicity of NLC (20- 200 μg/ml compritol) on macrophages and epithelial cells were revealed after 24h of incubation. NLC were highly uptaken by macrophages and epithelial cells in vitro. Besides, NLC showed higher antioxidant potential than β-caroten and showed high anti-inflammatory activity as measured by reduced production of TNF-α in lipopolysaccharide stimulated macrophages. These results suggest that NLC prepared with neutral and polar archaeal lipid are candidates as macrophages-targeted drug delivery systems that combined anti-inflammatory and anti-oxidant activities.