采用星点设计-效应面法优化及制备阿霉素白蛋白纳米粒

Optimization on the preparation of doxorubicin-loaded albumin nanoparticles using central composite design-response surface methodology

目的采用星点设计-效应面法优化阿霉素白蛋白纳米粒的制备工艺。方法采用去溶剂化-固化交联法制备阿霉素白蛋白纳米粒。以白蛋白质量浓度(X1:1ρ,g.L-1)、阿霉素的质量浓度(X2:2ρ,g.L-1)、pH值(X3)及白蛋白理论交联度(X4,%)为考察对象,以纳米粒平均粒径(Y1:d,nm)、zeta电位(Y2:V,mV)、载药量(Y3:w1,%)和包封率(Y4:w2,%)为评价指标,以四因素五水平的星点设计-效应面法筛选出最佳制备工艺;并采用透射电镜观察制得纳米粒的形态。结果优化后的处方工艺为:白蛋白质量浓度为17 g.L-1、阿霉素质量浓度为2 g.L-1、pH值为9、白蛋白理论交联度为125%。以此条件制得的纳米粒平均粒径为(151±0.43)nm,zeta电位为-(18.8±0.21)mV,载药量为(21.4±0.70)%,包封率为(76.9±0.21)%,均与预测值偏差较小。结论阿霉素白蛋白纳米粒的制备采用星点设计-效应面法设计并优化是可行的。

Objective To optimize the preparation of doxorubicin-loaded albumin nanoparticles using response surface methodology（RSM）.Methods Albumin nanoparticles were prepared through a desolvation method and optimized in the aid of central composite design.Albumin concentration（X1：ρ1,g·L-1）,amount of doxorubicin（X2：ρ2,g·L-1）,pH values（X3）,and theoretical degree of crosslinking of albumin（X4,%）were selected as independent variables,and nanoparticle size,zeta potential,drug loading and encapsulation efficiency as response variables.A central composite design（CCD）for four factors at five levels was used in this study.Response surface methodology and multiple response optimizations utilizing a quadratic polynomial equation were used to obtain an optimal formulation.The appearance and shape of the particles were also researched through transmission electron microscope.Results In the optimal formulation for doxorubicin-loaded albumin nanoparticles was as follows：albumin concentration was 17 g·L-1,amount of doxorubicin was 2 g·L-1,pH value was 9 and theoretical degree was 125% crosslinking of albumin;under the optimized conditions,the average value of mean particle size was（151±0.43）nm,zeta potential was（-18.8±0.21）mV,drug loading efficiency was（21.4±0.70）%,drug entrapment efficiency was（76.9±0.21）%.Conclusions This study shows that the RSM-CCD method can efficiently and precisely be applied for the modeling of albumin nanoparticles.