Affiliation:
1. Curso de Farmacia, Area do Conhecimento de Ciencias da Vida, Universidade de Caxias do Sul (UCS), Caxias do Sul, Brazil
2. Centro de Terapia Genica, Servico de Pesquisa Experimental, Hospital de Clinicas de Porto Alegre (HCPA), Porto Alegre, Brazil
3. Ciencias Farmaceuticas da Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
Abstract
Background:
Mucopolysaccharidosis type I (MPS I) is an inherited disorder caused by
α-L-iduronidase (IDUA) deficiency. The available treatments are not effective in improving all
signs and symptoms of the disease.
Objective:
In the present study, we evaluated the transfection efficiency of repeated intravenous administrations of cationic nanoemulsions associated with the plasmid pIDUA (containing IDUA gene).
Methods:
Cationic nanoemulsions were composed of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(amino[polyethylene glycol]-2000) (DSPE-PEG), 1,2-dioleoyl-sn-glycero-3-trimethylammonium propane (DOTAP), medium chain triglycerides, glycerol, and water and were prepared by high-pressure homogenization and were repeatedly administered to MPS I mice for IDUA production and gene expression.
Results:
A significant increase in IDUA expression was observed in all organs analyzed, and IDUA
activity tended to increase with repeated administrations when compared to our previous report
when mice received a single administration of the same dose. In addition, GAGs were partially
cleared from organs, as assessed through biochemical and histological analyzes. There was no presence
of inflammatory infiltrate, necrosis, or signs of an increase in apoptosis. Furthermore, immunohistochemistry
for CD68 showed a reduced presence of macrophage cells in treated than in
untreated MPS I mice.
Conclusion:
These set of results suggest that repeated administrations can improve transfection efficiency of cationic complexes without significant increase in toxicity in the MPS I murine model.
Funder
FIPE/HCPA
Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil
National Council for Scientific and Technological Development
Publisher
Bentham Science Publishers Ltd.
Subject
Genetics (clinical),Drug Discovery,Genetics,Molecular Biology,Molecular Medicine
Cited by
3 articles.
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