Kiafar Farhad, Siahi Shadbad Mohammad Reza, Valizadeh Hadi
Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran ; Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Bioimpacts. 2016;6(4):195-201. doi: 10.15171/bi.2016.26. Epub 2016 Dec 29.
Optimization of filgrastim (G-CSF) (granulocyte colony stimulating factor) liposomes formulation prepared by the method of film hydration was the aim of this research. To study the independent variables effects in the development of filgrastim (G-CSF) liposomes, method of factorial design was applied. The molar ratio of dipalmitoyl phophatidylcholine (DPPC) per cholesterol (Chol.) and hydration time were chosen as two independent factors. The dependent variables were encapsulation efficiency percent (EE %) and particle size (PS). Ultrafiltration method was applied for separation of un-encapsulated protein. RP-HPLC method was employed for analysis of G-CSF. Application of response surface methodology (RSM) in formulation of filgrastim liposomes and the obtained results for responses including particle size and EE % showed that the main effective independent variable was DPPC/Chol molar ratio. Different impacts of influencing parameters including interaction and individual effects were checked employing a mathematical method for obtaining desired liposomes. Optimum liposomal formulations were established using this method for enhancing their characteristics. Average percent errors (APEs) were 3.86% and 3.27% for predicting EE % and PS, respectively which reflect high model ability in this regard. It is concluded that observed and predicted values regarding PS and EE % were consistent and this model is efficient enough in prediction of the mentioned characteristics while preparing filgrastim (G-CSF) liposomes.
本研究旨在优化采用薄膜水化法制备的非格司亭(G-CSF,粒细胞集落刺激因子)脂质体配方。为研究非格司亭(G-CSF)脂质体开发过程中自变量的影响,应用了析因设计方法。选择二棕榈酰磷脂酰胆碱(DPPC)与胆固醇(Chol.)的摩尔比和水化时间作为两个自变量。因变量为包封率百分比(EE%)和粒径(PS)。采用超滤法分离未包封的蛋白质。采用反相高效液相色谱法分析G-CSF。响应面法(RSM)在非格司亭脂质体制备中的应用以及粒径和EE%等响应的所得结果表明,主要有效的自变量是DPPC/Chol摩尔比。采用数学方法检查包括相互作用和个体效应在内的影响参数的不同影响,以获得所需的脂质体。使用该方法建立了最佳脂质体配方以增强其特性。预测EE%和PS的平均百分误差(APE)分别为3.86%和3.27%,这反映了该模型在这方面的高能力。得出的结论是,关于PS和EE%的观察值和预测值是一致的,并且该模型在制备非格司亭(G-CSF)脂质体时对上述特性的预测足够有效。