星点设计-响应面法优化石杉碱甲-木犀草素脂质立方液晶纳米粒处方及其理化性质考察

Optimization of the Formulation of HupA-Lut liquid crystalline nanoparticles by Central Composite Design-response Surface Methodology and Their Physicochemical Properties

关键词:  石杉碱甲  木犀草素  脂质立方液晶纳米粒  处方优化  星点设计-响应面法

Key words:  huperzine A  luteolin  liquid crystalline nanoparticles  prescription optimization  central composite design-response surface method

摘要:

摘要：目的 优化石杉碱甲-木犀草素脂质立方液晶纳米粒处方，并考察其理化性质。方法 采用自下而上法（Bottom-up，BU法）制备石杉碱甲-木犀草素脂质立方液晶纳米粒。在单因素考察制备工艺及处方的基础上，以单油酸甘油酯含量（X1）、泊洛沙姆407含量（X2）、木犀草素含量（X3）为考察因素，以石杉碱甲包封率（Y1）、木犀草素的包封率（Y2）及平均粒径（Y3）为评价指标，并将三者线性归一化，通过星点设计-响应面法优化脂质立方液晶纳米粒处方。并对脂质立方液晶纳米粒的粒径、光学性质及晶型结构等理化性质进行考察。结果优化的处方为单油酸甘油酯质量含量7.50%，泊洛沙姆407含量1.07%，木犀草素含量0.26%。在此条件下，石杉碱甲包封率为（54.27±0.71）%，木犀草素的包封率为（90.89±1.18）%，平均粒径为（176.87±5.44）nm，多分散指数为0.118±0.022，Zeta电位为（-21.06±0.33）mv。石杉碱甲-木犀草素脂质立方液晶纳米粒在透射电镜下呈类球形，偏光显微镜下为暗视野、无双折射，X射线小角散射仪显示其内部结构属于双菱形（Pn3m）晶格结构。结论星点设计-响应面法建立的响应方程具有较好的预测性，可用于石杉碱甲-木犀草素脂质立方液晶纳米粒处方的优化,制备的脂质立方液晶纳米粒属于双菱形晶格结构，粒径小且分布均匀，性质稳定。

Abstract:

ABSTRACT: OBJECTIVE To optimize the formulation of liquid crystalline nanoparticles (LCNs) loaded with HupA-Lut and investigate their physicochemical properties.METHODS The Bottom-up method was used to prepare liquid crystalline nanoparticles loaded with HupA-Lut. Based on single-factor investigation of preparation process and prescription, Taking GMO content(X1), P407 content(X2) and Lut content(X3) as the inspection factors, central composite design-response surface methodology (CCD-RSM) and overall desirability were used to optimize the formulation with the encapsulation efficiency of HupA (Y1), the encapsulation efficiency of Lut(Y2) and average particle size(Y3) as evaluation indicators. The physicochemical properties of liquid crystalline nanoparticles such as particle size , Optical properties and crystal structure were investigated. RESULTS The optimal formulation was determined as follows: GMO content of 7.50%, P407 content of 1.07% and Lut content of 0.26%. Under these conditions, the encapsulation efficiency of HupA was (54.27±0.71)%, the encapsulation efficiency of Lut was (90.89±1.18)% , the average particle size was (176.87±5.44）nm, and the PDI was 0.118±0.022, the Zeta potential was (-21.06±0.33) mv.The liquid crystalline nanoparticles loaded with HupA-Lut exhibited a spherical shape under transmission electron microscopy.Under a polarizing microscope, a dark field was observed without birefringence.The X-ray smallangle scatterometer revealed that the internal structureof the nanoparticles belong to a double rhombohedral (Pn3m) lattice structure. CONCLUSION The response equation established by CCD-RSM demonstrated good predictability and can be used to optimize the formulation of HupA-Lut loaded LCNs.The prepared HupA-Lut loaded LCNs exhibited a double rhombohedral lattice structure, with small particle size, uniform distribution, and stable properties.