NANOMEDICINES FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASES.

HIGA LETICIA; JEREZ HORACIO; ROMERO EDER; MORILLA MARIA JOSE

Mar del Plata

Congreso; Reunión Conjunta 2016 entre la Sociedad Argentina de Investigación Clínica (SAIC), la Sociedad Argentina de Inmunología (SAI) y la Sociedad Argentina de Farmacología Experimental (SAFE); 2016

Sociedad Argentina de Investigación Clínica (SAIC), la Sociedad Argentina de Inmunología (SAI) y la Sociedad Argentina de Farmacología Experimental (SAFE)

Inflammatory bowel diseases such as Crohn?s diseaseand ulcerative colitis, are chronic relapsing disorders of thegastrointestinal tract, characterized bychronic inflammationand epithelial injuryinduced by the uncontrolled activationof the mucosal immune system. Dendritic cells andmacrophages are key cells in the inflamed mucosa, whichproduce large amounts of pro-inflammatory cytokines.The current treatment is symptomatic, but the frequentoral intake of anti-inflammatory and immunosuppressantdrugs or the systemic administration of biological agentssuch as the anti-TNF antibody infliximabis poorly effectiveand cause serious adverse effects.More efficacious and safer therapies could rely ondeveloping macrophages-targeted nanoparticles capableof specifically delivering high doses of immunosuppressantoranti-inflammatory drugs with minimal exposure ofhealthy. To that aim, we developedarchaeolipid nanoparticlesmade of a core of solid lipid and a shell of total polararchaeolipids (TPA) extracted from the halophilic archaebacterialHalorubrumtebenquichense. TPA are a mixtureof saturated isoprenoid chains linked via ether bonds tothe glycerol carbons at the sn2,3 position. In contrast toconventional phospholipids, TPA are hydrolytic, oxidativeand enzymatic attack resistant. Besides, TPA are ligandsfor the macrophages scavenger receptors class A. Archaeolipidnanoparticles would combine high resistanceunder gastric tract with extensive uptake by macrophages.Overall, our studies showed that ultra-small, highlynegatively charge mucopenetratingarchaeolipid nanoparticlesloaded with dexamethasone, but no nanoparticleslacking TPA, resulted highly stable under gastrointestinalconditions, were highly up taken by macrophages andreduced the secretion of pro-inflammatory cytokines frommacrophages stimulated with lipopolysaccharide. Weconsider that archaeolipid nanoparticlescould improvethe current therapies of inflammatory bowel diseases.