Superoxide dismutase enzymosomes: carrier capacity optimization, in vivo behaviour and therapeutic activity

M Luísa Corvo; H Susana Marinho; Paulo Marcelino; Rui M Lopes; Carlos A Vale; Claúdia R Marques; Luísa C D Martins; Peter Laverman; G Storm; M Bárbara A F Martins

doi:10.1007/s11095-014-1447-7

Superoxide dismutase enzymosomes: carrier capacity optimization, in vivo behaviour and therapeutic activity

M Luísa Corvo, H Susana Marinho, Paulo Marcelino, Rui M Lopes, Carlos A Vale, Claúdia R Marques, Luísa C D Martins, Peter Laverman, G Storm, M Bárbara A F Martins

Pharmaceutics

Research output: Contribution to journal › Article › Academic › peer-review

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: 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.

Original language	English
Pages (from-to)	91-102
Number of pages	12
Journal	Pharmaceutical Research
Volume	32
Issue number	1
DOIs	https://doi.org/10.1007/s11095-014-1447-7
Publication status	Published - Jan 2015

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art%3A10.1007%2Fs11095-014-1447-7Final published version, 550 KBLicence: Taverne

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title = "Superoxide dismutase enzymosomes: carrier capacity optimization, in vivo behaviour and therapeutic activity",

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: 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.",

author = "Corvo, {M Lu{\'i}sa} and Marinho, {H Susana} and Paulo Marcelino and Lopes, {Rui M} and Vale, {Carlos A} and Marques, {Cla{\'u}dia R} and Martins, {Lu{\'i}sa C D} and Peter Laverman and G Storm and Martins, {M B{\'a}rbara A F}",

year = "2015",

month = jan,

doi = "10.1007/s11095-014-1447-7",

language = "English",

volume = "32",

pages = "91--102",

journal = "Pharmaceutical Research",

issn = "0724-8741",

publisher = "Springer",

number = "1",

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TY - JOUR

T1 - Superoxide dismutase enzymosomes

T2 - carrier capacity optimization, in vivo behaviour and therapeutic activity

AU - Corvo, M Luísa

AU - Marinho, H Susana

AU - Marcelino, Paulo

AU - Lopes, Rui M

AU - Vale, Carlos A

AU - Marques, Claúdia R

AU - Martins, Luísa C D

AU - Laverman, Peter

AU - Storm, G

AU - Martins, M Bárbara A F

PY - 2015/1

Y1 - 2015/1

N2 - 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: 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.

AB - 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: 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.

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DO - 10.1007/s11095-014-1447-7

M3 - Article

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SN - 0724-8741

VL - 32

SP - 91

EP - 102

JO - Pharmaceutical Research

JF - Pharmaceutical Research

IS - 1

ER -

Superoxide dismutase enzymosomes: carrier capacity optimization, in vivo behaviour and therapeutic activity

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