Transport mechanism of doxorubicin loaded chitosan based nanogels across intestinal epithelium.
Eur J Pharm Biopharm
; 87(1): 197-207, 2014 May.
Article
en En
| MEDLINE
| ID: mdl-24316340
ABSTRACT
Chitosan/carboxymethyl chitosan nanogels (CS/CMCS-NGs) could enhance the oral bioavailability of doxorubicin hydrochloride (DOX). To identify the mechanisms that support this recent observation, different transport pathways of CS/CMCS-NGs through the small intestine were studied in this work. Transcellular mechanisms were investigated in the presence of different inhibitors of protein-mediated endocytosis. A reduction of 52.32±18% of drug transport was found when clathrin-mediated endocytosis was inhibited, which demonstrated that clathrin-mediated endocytosis played an important role in the transcellular transport of DOXCS/CMCS-NGs. The paracellular transport results showed that CMCS in NGs could produce a transient and reversible enhancement of paracellular permeability by depriving Ca(2+) from adherens junctions, whose efficacy as an absorption enhancer was about 1.7-3.3 folds higher than CS in NGs in GI tract. Finally, in vivo experiment showed that the transport capacity of DOXCS/CMCS-NGs was significantly inhibited by extra added Ca(2+), which confirmed that the higher capacity to binding Ca(2+) of CS/CMCS-NGs was beneficial for transport of DOX.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Portadores de Fármacos
/
Doxorrubicina
/
Quitosano
/
Nanoestructuras
/
Mucosa Intestinal
/
Antibióticos Antineoplásicos
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Eur J Pharm Biopharm
Asunto de la revista:
FARMACIA
/
FARMACOLOGIA
Año:
2014
Tipo del documento:
Article
País de afiliación:
China