【作者】 李国锋； 任非； 陈如大； 孙亚彬； 刘思佳； 侯连兵；

【机构】 南方医科大学南方医院药学部； 广东省佛山市南海区人民医院；

【摘要】 <正>Purpose.The aim of this study was to test the ability of paclitaxel-loaded poly(butyl) cyanoacrylate(PBCA) nanoparticles to overcome multidrug resistance(MDR) in human ovarian resistant cells(A2780/T) and investigate its possible mechanism. Methods.We prepared paclitaxel-loaded PBCA nanoparticles by interfacial polymerization method.The physicochemistry of the nanoparticles were characterized.The cytotoxicity of paclitaxel-loaded PBCA nanoparticles was measured by MTT assay.Calcein-AM assay was used to analyze the P-glycoprotein(P-gp) function and the expression of MDR-1 mRNA in A2780/T cells treated with drug-loaded nanoparticles was defined by QRT-PCR. Results.The nanoparticles were approximately spherical in shape with an average diameter of 224.5±5.7 nm.The encapsulation efficiency was 99.23%.The in vitro drug release profile exhibited a biphasic pattern.The drug formulated in PBCA nanoparticles showed a greater cytotoxicity than paclitaxel against A2780/T cells.Paclitaxel-loaded PBCA as well as blank PBCA nanoparticles decreased P-gp function in a dose-dependent manner,suggesting the efficacy of the drug-loaded nanoparticle system on overcoming MDR.There had no significant effect on inhibition to the expression of MDR 1 mRNA. Conclusion.Paclitaxel-loaded PBCA nanoparticles can enhance cytotoxicity and overcome MDR through a mechanism of the inhibition of P-gp function caused by the nanoparticles system.更多还原

【Abstract】 Purpose.The aim of this study was to test the ability of paclitaxel-loaded poly(butyl) cyanoacrylate(PBCA) nanoparticles to overcome multidrug resistance(MDR) in human ovarian resistant cells(A2780/T) and investigate its possible mechanism. Methods.We prepared paclitaxel-loaded PBCA nanoparticles by interfacial polymerization method.The physicochemistry of the nanoparticles were characterized.The cytotoxicity of paclitaxel-loaded PBCA nanoparticles was measured by MTT assay.Calcein-AM assay was used to analyze the P-glycoprotein(P-gp) function and the expression of MDR-1 mRNA in A2780/T cells treated with drug-loaded nanoparticles was defined by QRT-PCR. Results.The nanoparticles were approximately spherical in shape with an average diameter of 224.5±5.7 nm.The encapsulation efficiency was 99.23%.The in vitro drug release profile exhibited a biphasic pattern.The drug formulated in PBCA nanoparticles showed a greater cytotoxicity than paclitaxel against A2780/T cells.Paclitaxel-loaded PBCA as well as blank PBCA nanoparticles decreased P-gp function in a dose-dependent manner,suggesting the efficacy of the drug-loaded nanoparticle system on overcoming MDR.There had no significant effect on inhibition to the expression of MDR 1 mRNA. Conclusion.Paclitaxel-loaded PBCA nanoparticles can enhance cytotoxicity and overcome MDR through a mechanism of the inhibition of P-gp function caused by the nanoparticles system.更多还原