【摘要】 目的制备载米托蒽醌-磁性纳米氧化铁多功能脂质体(mitoxantrone-magnetic iron oxide nanoparticle loaded liposome,Mit-MLs),研究其理化特性和体内药代动力学特征。方法采用薄膜-超声分散法和硫酸铵梯度法制备Mit-MLs,测定其粒径及分布、包封率和药物体外释放特征,用临床用磁共振成像(MR)仪研究Mit-MLs的T2增强作用。采用HPLC法研究Mit-MLs在大鼠体内的药代动力学特征。结果 Mit-MLs的平均粒径为(120.2±0.35)nm,多分散系数为0.157 2,Zeta电位为(-14.4±0.85)mV,包封率约为(98.6±1.1)%。体外释放实验显示,Mit-MLs基本无药物突释现象,具有缓释特性。体外MR实验显示,Mit-MLs具有明显T2增强作用。大鼠体内药代动力学实验显示,与盐酸米托蒽醌游离药相比,Mit-MLs的半衰期显著延长(P<0.05),药-时曲线下面积(AUC)明显增加(P<0.05),表明盐酸米托蒽醌脂质体具有长循环的特点。结论 Mit-MLs具有有高包封率、均匀的粒径及分布、缓释特性、能够增加AUC,延长药物半衰期,具有T2增强作用,有望成为肿瘤个体化治疗中的优良载体。更多还原

【Abstract】 OBJECTIVE To prepare mitoxantrone-magnetic iron oxide nanoparticle loaded liposome(Mit-MLs),evaluate its physical and chemical properties as well as pharmacokinetics properties in vivo.METHODS Mit-MLs were prepared by thin film hydration-ultrasonic combined with ammonium sulphate gradients method.The prepared liposomes were characterized in terms of particle size and size distribution,drug encapsulation efficiency and in vitro release characteristic.The in vitro T2 enhancement was evaluated on clinical MR scanner.The in vivo pharmacokinetics was evaluated in rats by HPLC method.RESULTS The Mit-MLs showed nanometer size with the average particle diameter of(120.2±0.35)nm,polydispersity coefficient of 0.157 2,Zeta potential of(-14.4±0.85)mV and drug encapsulation efficiency of(98.6±1.1)%.The Mit-MLs exhibited a continuous and steady release of Mit without initial burst release.The Mit-MLs demonstrated good T2 enhancement in vitro MR detection.In the pharmacokinetics experiments,Mit-MLs displayed higher AUC(P<0.05)and longer t1/2(P<0.05)compared with free mitoxantrone,indicating its long circulating property.CONCLUSIONS The magnetic iron oxide nanoparticle-mitoxantrone loaded liposome had high drug encapsulating efficiency,more uniform size and size distribution,excellent stability,sustained release,long circulating property,improved AUC and half life,good T2 enhancement.Therefore,magnetic iron oxide nanoparticle-mitoxantrone loaded liposome will be an excellent carrier for personal antitumor therapy.更多还原