Enzymosomes with surface-exposed superoxide dismutase: in vivo behaviour and therapeutic activity in a model of adjuvant arthritis.
Acylated Superoxide Dismutase (Ac-SOD) enzymosomes, liposomal enzymatic systems expressing catalytic activity in the intact form, were previously characterized. The main scope of the present work was to investigate the biological behaviour of Ac-SOD inserted in the lipid bilayer of liposomes, in comparison with SOD located in the aqueous compartment of liposomes. Two types of liposomes were used: conventional liposomes presenting an unmodified external surface and long circulating liposomes coated with poly (ethylene glycol) (PEG). Liposomal formulations of Ac-SOD and SOD were prepared and labelled with indium-111 and their in vivo fate compared. Data obtained led us to the conclusion that, for liposomes coated with PEG the in vivo fate was not influenced by the insertion of Ac-SOD in the lipid bilayers. The potential therapeutic effect of Ac-SOD enzymosomes was compared with SOD liposomes in a rat model of adjuvant arthritis. A faster anti-inflammatory effect was observed for Ac-SOD enzymosomes by monitoring the volume of the inflamed paws. The present results allowed us to conclude that Ac-SOD enzymosomes are nano-carriers combining the advantages of expressing enzymatic activity in intact form and thus being able to exert therapeutic effect even before liposomes disruption, as well as acting as a sustained release of the enzyme.
Gaspar
Maria Manuela
MM
Unidade Novas Formas de Agentes Bioactivos, Departamento de Biotecnologia, Instituto Nacional de Engenharia Tecnologia e Inovação, IP, Estrada do Paço do Lumiar, 22, 1649-038 Lisboa, Portugal.
Boerman
Otto C
OC
Laverman
Peter
P
Corvo
Maria Luísa
ML
Storm
Gert
G
Cruz
Maria Eugénia Meirinhos
ME
D000215:Acylation; D000588:Amines / Q000737:chemistry; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D003692:Delayed-Action Preparations / Q000737:chemistry; D004800:Enzymes, Immobilized / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007275:Injections, Intravenous; D008081:Liposomes / Q000737:chemistry; D008297:Male; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution; D016896:Treatment Outcome
D000588:Amines; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D003692:Delayed-Action Preparations; D004800:Enzymes, Immobilized; D008081:Liposomes; D011092:Polyethylene Glycols; D013482:Superoxide Dismutase; C009317:stearylamine