Cell-penetrating peptide-modified block copolymer micelles promote direct brain delivery via intranasal administration.
Pharm Res
; 28(9): 2130-9, 2011 Sep.
Article
en En
| MEDLINE
| ID: mdl-21499835
ABSTRACT
PURPOSE:
In order to develop non-invasive and effective nose-to-brain delivery of drugs, we synthesized Tat analog-modified methoxy poly(ethylene glycol) (MPEG)/poly(ε-caprolactone) (PCL) amphiphilic block copolymers through the ester bond.METHODS:
We evaluated the brain distribution of coumarin, acting as a model chemical, after intravenous or intranasal administration of MPEG-PCL. In addition, cellular uptake of coumarin by rat glioma cells transfected with coumarin-loaded MPEG-PCL or MPEG-PCL-Tat was determined. Finally, we determined the brain distribution and biodistribution after intranasal administration of coumarin-loaded MPEG-PCL-Tat.RESULTS:
The amount of coumarin in the brain after intranasal administration was significantly higher than that after intravenous administration. In addition, cellular uptake of coumarin using MPEG-PCL was the lowest, while cellular uptake of coumarin using Tat-modified MPEG-PCL (MPEG-PCL-Tat) was higher than that of MPEG-PCL. Therefore, the brain distribution of coumarin administered using MPEG-PCL-Tat was significantly greater than that using MPEG-PCL. Then, the coumarin distribution after MPEG-PCL-Tat administration in non-targeted tissues (lung, liver, heart, kidney and spleen) was lower than that after coumarin administration without nanomicelles.CONCLUSION:
We have demonstrated that utilization of nano-sized micelles modified with Tat can facilitate direct intranasal brain delivery.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
Poliésteres
/
Polietilenglicoles
/
Encéfalo
/
Portadores de Fármacos
/
Cumarinas
/
Productos del Gen tat del Virus de la Inmunodeficiencia Humana
/
Péptidos de Penetración Celular
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Pharm Res
Año:
2011
Tipo del documento:
Article
País de afiliación:
Japón