title: Superoxide dismutase enzymosomes: carrier capacity optimization, in vivo behaviour and therapeutic activity.
abstract: OBJECTIVE
  A strategy not usually used to improve carrier-mediated delivery of therapeutic enzymes is the attachment of the enzymes to the outer surface of liposomes. The aim of our work was to design a new type of enzymosomes with a sufficient surface-exposed enzyme load while preserving the structural integrity of the liposomal particles and activity of the enzyme.
  
  
  METHODS
  The therapeutic antioxidant enzyme superoxide dismutase (SOD) was covalently attached to the distal terminus of polyethylene glycol (PEG) polymer chains, located at the surface of lipid vesicles, to obtain SOD-enzymosomes.
  
  
  RESULTS
  The in vivo fate of the optimized SOD-enzymosomes showed that SOD attachment at the end of the activated PEG slightly reduced the residence time of the liposome particles in the bloodstream after IV administration. The biodistribution studies showed that SOD-enzymosomes had a similar organ distribution profile to liposomes with SOD encapsulated in their aqueous interior (SOD-liposomes). SOD-enzymosomes showed earlier therapeutic activity than both SOD-liposomes and free SOD in rat adjuvant arthritis. SOD-enzymosomes, unlike SOD-liposomes, have a therapeutic effect, decreasing liver damage in a rat liver ischemia/reperfusion model.
  
  
  CONCLUSIONS
  SOD-enzymosomes were shown to be a new and successful therapeutic approach to oxidative stress-associated inflammatory situations/diseases.
authors.affiliation: Intracellular Trafficking Modulation for Advanced Drug Delivery iMED.ULisboa, Faculdade de Farmácia, Universidade de Lisboa, Campus do Lumiar Estrada do Paço do Lumiar, 22, 1649-038, Lisbon, Portugal, lcorvo@ff.ul.pt.
authors.forename: M Luísa
authors.initials: ML
authors.lastname: Corvo
authors.forename: H Susana
authors.initials: HS
authors.lastname: Marinho
authors.forename: Paulo
authors.initials: P
authors.lastname: Marcelino
authors.forename: Rui M
authors.initials: RM
authors.lastname: Lopes
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Vale
authors.forename: Claúdia R
authors.initials: CR
authors.lastname: Marques
authors.forename: Luísa C D
authors.initials: LC
authors.lastname: Martins
authors.forename: Peter
authors.initials: P
authors.lastname: Laverman
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
authors.forename: M Bárbara A F
authors.initials: MB
authors.lastname: Martins
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D065546:Drug Liberation; D008081:Liposomes; D008099:Liver / Q000098:blood supply; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism; D013482:Superoxide Dismutase / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013499:Surface Properties; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D011092:Polyethylene Glycols; D013482:Superoxide Dismutase