Abstract | PURPOSE: 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: 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.
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Authors | M Luísa Corvo, H Susana Marinho, Paulo Marcelino, Rui M Lopes, Carlos A Vale, Claúdia R Marques, Luísa C D Martins, Peter Laverman, Gert Storm, M Bárbara A F Martins |
Journal | Pharmaceutical research
(Pharm Res)
Vol. 32
Issue 1
Pg. 91-102
(Jan 2015)
ISSN: 1573-904X [Electronic] United States |
PMID | 25037861
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Drug Carriers
- Liposomes
- Polyethylene Glycols
- Superoxide Dismutase
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Topics |
- Animals
- Arthritis, Experimental
(drug therapy, metabolism)
- Drug Carriers
(chemistry)
- Drug Compounding
- Drug Liberation
- Liposomes
- Liver
(blood supply)
- Male
- Oxidative Stress
(drug effects)
- Particle Size
- Polyethylene Glycols
(chemistry)
- Rats, Wistar
- Reperfusion Injury
(drug therapy, metabolism)
- Superoxide Dismutase
(administration & dosage, pharmacokinetics, therapeutic use)
- Surface Properties
- Tissue Distribution
- Treatment Outcome
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