Brain Targeting and Toxicological Assessment of the Extracellular Vesicle-Packaged Antioxidant Catalase-SKL Following Intranasal Administration in Mice.
Neurotox Res
; 39(5): 1418-1429, 2021 Oct.
Article
in En
| MEDLINE
| ID: mdl-34196954
ABSTRACT
The antioxidant enzyme catalase represents an important therapeutic target due to its role in mitigating cellular reactive oxygen species that contribute to the pathogenesis of many disease states. Catalase-SKL (CAT-SKL), a genetically engineered, peroxisome-targeted, catalase derivative, was developed in order to increase the therapeutic potential of the enzyme, and has previously been shown to be effective in combating oxidative stress in a variety of in vitro and in vivo models, thereby mitigating cellular degeneration and death. In the present study we addressed important considerations for the development of an extracellular vesicle-packaged version of CAT-SKL (evCAT-SKL) as a therapeutic for neurodegenerative diseases by investigating its delivery potential to the brain when administered intranasally, and safety by assessing off-target toxicity in a mouse model. Mice received weekly intranasal administrations of evCAT-SKL or empty extracellular vesicles for 4 weeks. Fluorescent labeling for CAT-SKL was observed throughout all sections of the brain in evCAT-SKL-treated mice, but not in empty extracellular vesicle-treated mice. Furthermore, we found no evidence of gross or histological abnormalities following evCAT-SKL or empty extracellular vesicle treatment in a full-body toxicological analysis. Combined, the successful brain targeting and the lack of off-target toxicity demonstrates that intranasal delivery of extracellular vesicle-packaged CAT-SKL holds promise as a therapeutic for addressing neurological disorders.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain
/
Administration, Intranasal
/
Catalase
/
Extracellular Vesicles
/
Antioxidants
Limits:
Animals
Language:
En
Journal:
Neurotox Res
Journal subject:
NEUROLOGIA
Year:
2021
Document type:
Article
Affiliation country:
Canada