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Curr Pharm Des ; 16(21): 2331-40, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20618154

RESUMO

Paclitaxel appears to be a potential substrate of the multidrug resistance protein p-glycoprotein, thus preventing itself from entry into the brain and penetrating blood-brain barrier poorly. In this study, the main objective was to design paclitaxel formulation using PLGA-based nanoparticles with different additives and surface coatings to facilitate the paclitaxel transport through MDCK cell monolayer. PLGA-based nanoparticles of around 200 nm without and with additives and surface coatings were developed by direct dialysis. The transendothelial electrical resistance (TEER) variation of MDCK cell monolayer on the cell inserts imposed by paclitaxel-loaded nanoparticles with and without additives was investigated. (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole) (MTT) assay was used to quantify the cell viability of C6 glioma cells after administration of formulations on the topical side. Investigations showed that particles with additives were able to enhance cellular uptake more than surface-coated particles. TEER values dropped upon the introduction of paclitaxel-loaded PLGA nanoparticles to the cell inserts. After incubation for 24 h, the cell viability of C6 glioma cells in the wells treated with nanoparticles was lower than that of the control wells without particles. Taken together, PLGA nanoparticles with vitamin E TPGS and polysorbate 80 as additives were successfully obtained as paclitaxel formulations, demonstrating great potential for the delivery of paclitaxel through MDCK cell monolayer in vitro.


Assuntos
Membrana Celular/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/administração & dosagem , Paclitaxel/administração & dosagem , Animais , Linhagem Celular , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Química Farmacêutica , Cães , Ácido Láctico/administração & dosagem , Ácido Láctico/química , Ácido Láctico/farmacocinética , Nanopartículas/química , Paclitaxel/química , Paclitaxel/farmacocinética , Ácido Poliglicólico/administração & dosagem , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
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