摘要
目的采用Box-Behnken效应面法优化贝伐单抗介导的阿霉素白蛋白纳米粒制备工艺。方法在采用去溶剂化-固化交联法制备出的阿霉素白蛋白纳米粒的基础上,用异型双功能交联剂NHS-PEG3500-MAL作为偶联剂,将贝伐单抗偶联到载药白蛋白纳米粒表面。以2-亚氨基硫烷盐酸盐用量、载药白蛋白纳米粒与贝伐单抗质量比、NHS-PEG3500-MAL用量为影响因素,以纳米粒粒径、载药量和包封率作为评价指标,用三因素三水平的Box-Be-hnken效应面法设计试验,并对免疫纳米粒的制备进行优化;考察制备出的免疫纳米粒的抗体活性保存率及稳定性。结果优化后的处方是2-亚氨基硫烷盐酸盐50μg、DOX-A-NPs与Bevacizumab质量比为27.5 mg.mg-1、NHS-PEG3500-MAL用量为8.8 mg,以此处方制得的免疫纳米粒粒径为(216.1±2.31)nm、载药量为(28.93±0.94)%、包封率为(80.39±2.83)%,测得值与预测值相差较小。结论采用Box-Behnken效应面法优化并制备阿霉素白蛋白免疫纳米粒是可行的。
Objective To optimize the preparation of bevacizumab-mediated,doxorubicin-loaded albumin nanoparticles with Box-Behnken design-response surface methodology.Methods Based on the preparation of doxorubicin-loaded albumin nanoparticles,hetero-bifunctional crosslinker NHS-PEG3500-MAL was employed to couple bevacizumab with drug-loaded albumin nanoparticles.The amount of 2-iminothiolane,weight-ratio of drug-loaded albumin nanoparticles and bevacizumab,and the amount of crosslinker were used as influencing factors,and mean particle size,drug-loading,entrapment efficiency as response variables.A design of 3 factors at 3 levels was made with the aid of Box-Behnken design-response surface methodology.The conservation ratio and the storage ability of prepared immuno-nanoparticles were also investigated.Results In the optimized formulation for immuno-nanoparticles,the amount of 2-iminothiolane was 50 μg,the weight-ratio of drug-loaded albumin nanoparticles was 27.5 mg·mg-1 and bevacizumab,and the amount of NHS-PEG3500-MAL was 8.8 mg.The prepared immuno-nanoparticles had a mean particle size of 216.1±2.31 nm,drug loading of（28.93±0.94）% and entrapment efficiency（80.39±2.83）%,with a minor predicted error.Conclusion It is feasible to optimize the preparation of doxorubicin-loaded albumin immuno-nanoparticles through Box-Behnken design-response surface methodology.
出处
《中南药学》
CAS
2011年第9期641-644,共4页
Central South Pharmacy
