Box-Behnken响应面法优化羟基红花黄色素A纳米粒处方工艺及体外释放评价  

Formulation Optimization of Hydroxyylsafflower Yellow A Nanoparticle Using Box-Behnken Response Surface Method and in Vitro Release Evaluation

作　　者：肖奕菲 杜利新 魏起东 陆慧玲 郭志华[1] 李雅[1] XIAO Yifei;DU Lixin;WEI Qidong;LU Huiling;GUO Zhihua;LI Ya(Hunan University of Chinese Medicine,Changsha 410208 Hunan,China)

机构地区：[1]湖南中医药大学,湖南长沙410208

出　　处：《中药新药与临床药理》2024年第1期122-131,共10页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：湖南省卫生健康委科研课题(D202303017861);湖南中医药大学中药学一流学科建设项目(4901-0200002006);湖南中医药大学校级研究生培养质量工程项目(2022CX78)。

摘　　要：目的优化羟基红花黄色素A(hydroxysafflor yellow A,HSYA)纳米粒制备工艺,并对其进行体外释放评价。方法以乳酸-羟基乙酸共聚物[poly(lactic-co-glycolicacid),PLGA]为载体,利用改良的复乳法制备HSYA纳米粒,通过Plackett-Burman设计实验联用Box-Behnken响应面法优选最佳制备工艺;利用粒径测定仪、TEM扫描电镜仪、傅里叶红外光谱(FT-IR)仪、X-射线粉末衍射(XRD)仪对纳米粒进行表征;并对其进行4℃储藏稳定性、生理介质中稳定性、冻干保护剂及体外释放率考察。结果优选出纳米粒最佳工艺处方为:pH为6.95,投药量为2.8 mg,载体用量为18.2 mg;在此条件下制备出的纳米粒粒径为(176.4±1.29)nm,多分散系数(Polydiseperse Index,PDI)为(0.152±0.014),Zeta电位为(-17.6±0.46)mV,包封率为(78.5±0.49)%,载药量为(7.3±0.07)%,纳米粒形态圆整,分散性好;在4℃储存环境下、不同生理介质中稳定性良好,最佳冻干保护剂为1%葡萄糖;纳米粒48 h体外释放率为85%。结论该优化方法合理可靠,所得纳米粒稳定性良好,具有一定的缓释作用,体外释放符合一级动力学模型。Objective To optimize the preparation process of hydroxysafflor yellow A(HSYA)nanoparticle and conduct in vitro release evaluation.Methods HSYA nanoparticles were prepared with PLGA as carrier by modified compound emulsion method.The optimal preparation process of the experiment was selected by Plackett-Burman and Box-Behnken response surface method.The nanoparticles were characterized by using particle size analyzer,TEM scanning electron microscope,Fourier transform infrared spectroscopy(FT-IR),X-ray diffraction(XRD).Frozen(4℃)storage stability,stability in physiological medium,lyophilized protective agent and in vitro release rate were investigated.Results The optimal process prescription of nanoparticle is as follow:pH value is 6.95,the dosage is 2.8 mg,and carrier dosage is 18.2 mg.The size of nanoparticles obtained at optimum condition is(176.4±1.29)nm,the polydiseperse index(PDI)is 0.152±0.014,the Zeta potential is(-17.6±0.46)mV,the encapsulation rate is(78.5±0.49)%,drug loading is(7.3±0.07)%.These nanoparticles showed round and good dispersion.Good stability in 4℃storage environment and different physiological media of nanoparticles were observed.The best lyophilized protective agent was 1%glucose and the in vitro release rate of nanoparticles at 48 hours was 85%.Conclusion The optimization method is reasonable and reliable.The obtained nanoparticles have good stability and sustained-release effect.The in vitro release behavior conformed to first-order kinetic model.

关 键 词：羟基红花黄色素A PLGA纳米粒 Plackett-Burman设计实验 Box-Behnken响应面法 体外释放 

分 类 号：R283.6[医药卫生—中药学]