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Drug Deliv ; 25(1): 872-879, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29608119

RESUMO

The aim of this study was to investigate the effectiveness of treating gastric cancer by injecting a pluronic F-127 sol-gel formulation of 5-fluorouracil (5-FU) into normal tissue surrounding the tumor using a hollow microneedle. The MTS tetrazolium assay was performed to assess the cytotoxicity of 5-FU after application to gastric cancer cells at different concentrations for 1, 5 and 10 h. Gastric cancer cells were inoculated subcutaneously into 30 male nude mice (CrjBALB/c-nu/nu mice, male); the inoculated mouse were divided into three groups. One group received no treatment, whereas the two other groups received free 5-FU gel (40 mg/kg) and 5-FU gel (40 mg/kg) for 4 days, respectively. Mean tumor volume, apoptotic index (TUNEL) and proliferative index (Ki 67) were evaluated in all groups. Cell viability was 77.3% when 1.22 g of free 5-FU was administered, whereas cell viability was 37.4% and 43.5% when 0.122 g of free 5-FU was administered per hour for 10 h and 0.244 g of free 5-FU was administered for 5 h (p < .01). The 5-FU sol-gel induced apoptosis and significantly inhibited cell proliferation compared to the free 5-FU (p < .01). In addition, xenografted tumor growth was significantly suppressed by administration of the 5-FU sol-gel formulation to inoculated mice (p < .01), and 71% (5/7) of xenografted tumors disappeared after 4 weeks. In conclusion, peri-tumor injection of a 5-FU sol-gel formulation into normal tissue surrounding the tumor mass using a hollow microneedle is an effective method for treating gastric cancer.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Portadores de Fármacos , Fluoruracila/administração & dosagem , Agulhas , Poloxâmero/química , Neoplasias Gástricas/tratamento farmacológico , Animais , Antimetabólitos Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Preparações de Ação Retardada , Composição de Medicamentos , Liberação Controlada de Fármacos , Desenho de Equipamento , Fluoruracila/química , Humanos , Injeções Intralesionais , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Miniaturização , Transição de Fase , Solubilidade , Neoplasias Gástricas/patologia , Fatores de Tempo , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
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