NANOMEDICINES FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASES.

HIGA L; HORACIO JEREZ; EDER L. ROMERO; MORILLA MJ

Mar del Plata

Congreso; Congreso Anual SAIC SAI SAFE; 2016

SAIC-SAI-SAFE-Nanomed-ar

NANOMEDICINES FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASES. HIGA L, JEREZ H, ROMERO E, MORILLA MJ. Nanomedicine ResearchProgram, Universidad Nacional de Quilmes, Buenos Aires, Argentina Inflammatory bowel diseases such as Crohn?s disease and ulcerative colitis, are chronic relapsing disorders of the gastrointestinal tract, characterized bychronic inflammation and epithelial injuryinduced 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. The current treatment is symptomatic, but the frequent oral intake of anti-inflammatory and immunosuppressant drugs or the systemic administration of biological agents such as the anti-TNF antibody infliximabis poorly effective and cause serious adverse effects. More efficacious and safer therapies could rely on developing macrophages-targeted nanoparticles capable of specifically delivering high doses of immunosuppressantor anti-inflammatory drugs with minimal exposure of healthy. To that aim, we developedarchaeolipid nanoparticles made of a core of solid lipid and a shell of total polar archaeolipids (TPA) extracted from the halophilic archaebacterial Halorubrumtebenquichense. TPA are a mixture of saturated isoprenoid chains linked via ether bonds to the glycerol carbons at the sn2,3 position. In contrast to conventional phospholipids, TPA are hydrolytic, oxidative and enzymatic attack resistant. Besides, TPA are ligands for the macrophages scavenger receptors class A. Archaeolipid nanoparticles would combine high resistance under gastric tract with extensive uptake by macrophages. Overall, our studies showed that ultra-small, highly negatively charge mucopenetratingarchaeolipid nanoparticles loaded with dexamethasone, but no nanoparticles lacking TPA, resulted highly stable under gastrointestinal conditions, were highly up taken by macrophages and reduced the secretion of pro-inflammatory cytokines from macrophages stimulated with lipopolysaccharide. We consider that archaeolipid nanoparticlescould improve the current therapies of inflammatory bowel diseases.