Reductively Responsive Hydrogel Nanoparticles with Uniform Size, Shape, and Tunable Composition for Systemic siRNA Delivery in Vivo.
Mol Pharm
; 12(10): 3518-3526, 2015 Oct 05.
Article
en En
| MEDLINE
| ID: mdl-26287725
ABSTRACT
To achieve the great potential of siRNA based gene therapy, safe and efficient systemic delivery in vivo is essential. Here we report reductively responsive hydrogel nanoparticles with highly uniform size and shape for systemic siRNA delivery in vivo. "Blank" hydrogel nanoparticles with high aspect ratio were prepared using continuous particle fabrication based on PRINT (particle replication in nonwetting templates). Subsequently, siRNA was conjugated to "blank" nanoparticles via a disulfide linker with a high loading ratio of up to 18 wt %, followed by surface modification to enhance transfection. This fabrication process could be easily scaled up to prepare large quantity of hydrogel nanoparticles. By controlling hydrogel composition, surface modification, and siRNA loading ratio, siRNA conjugated nanoparticles were highly tunable to achieve high transfection efficiency in vitro. FVII-siRNA conjugated nanoparticles were further stabilized with surface coating for in vivo siRNA delivery to liver hepatocytes, and successful gene silencing was demonstrated at both mRNA and protein levels.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Sistemas de Liberación de Medicamentos
/
Hidrogeles
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ARN Interferente Pequeño
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Nanopartículas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Pharm
Asunto de la revista:
BIOLOGIA MOLECULAR
/
FARMACIA
/
FARMACOLOGIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos