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Pharm Res ; 19(3): 246-9, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11934229

RESUMO

PURPOSE: We delivered interleukin-4 (IL-4) plasmid (pCAGGS-IL-4) using the biodegradable polymer, poly[alpha-(4-aminobutyl)-L-glycolic acid] (PAGA), to prevent autoimmune insulitis in NOD mice. METHODS: The pCAGGS-IL-4/PAGA complex was transfected to 293T cells. The expression level of IL-4 was measured by ELISA. The pCAGGS IL-4/PAGA complex was injected once to NOD mice intravenously at the age of 4 weeks. RT-PCR was performed to evaluate the level of the IL-4 mRNA in the liver. At 6 weeks after the injection, the grade of insulitis of the mice was evaluated by double blind methods. RESULTS: In vitro transfecton assays showed that PAGA enhanced the expression of IL-4 in 293T cells. RT-PCR of the liver showed that IL-4 was expressed highest in the complex injected group. In the plasmid/PAGA complex injected group, the prevalence of severe insulitis in NOD mice was markedly improved, suggesting that PAGA enhanced the delivery of IL-4 plasmid. CONCLUSION: The pCAGGS-IL-4/PAGA complex is an effective system to prevent autoimmune insulitis in NOD mice and applicable for the prevention of autoimmune diabetes.


Assuntos
Diabetes Mellitus Tipo 1/prevenção & controle , Sistemas de Liberação de Medicamentos/métodos , Interleucina-4/administração & dosagem , Interleucina-4/genética , Ilhotas Pancreáticas/imunologia , Ilhotas Pancreáticas/patologia , Plasmídeos/administração & dosagem , Ácido Poliglicólico/análogos & derivados , Animais , Linhagem Celular , Diabetes Mellitus Tipo 1/metabolismo , Portadores de Fármacos/administração & dosagem , Feminino , Terapia Genética/métodos , Ilhotas Pancreáticas/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Ácido Poliglicólico/administração & dosagem , Solubilidade
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