基于响应面法优化脂质纳米颗粒的配方及表征
Optimization and characterization of lipid nanoparticles based on response surface method
麻玉清 1柳海云 2郭伟 3江丽馨 2孙世琪 2王晓强 3马全英 3郭慧琛2
作者信息
- 1. 兰州交通大学化学 化工学院,甘肃兰州 730070;中国农业科学院 兰州兽医研究所兰州大学动物医学与生物安全学院 动物疫病防控全国重点实验室,甘肃兰州 730046
- 2. 中国农业科学院 兰州兽医研究所兰州大学动物医学与生物安全学院 动物疫病防控全国重点实验室,甘肃兰州 730046
- 3. 兰州交通大学生物与制药工程学院,甘肃兰州 730070
- 折叠
摘要
脂质纳米颗粒是目前最有应用前景的药物载体之一,本研究旨在解决原材料配方对脂质纳米颗粒自组装的影响,优化其配方.首先,以包封率为评价指标,通过单因素试验确定膜材比、脂质浓度和DMG-PEG 2000 的含量.其次,采用Box-Benhnken响应面分析法优化脂质纳米颗粒制备工艺,并对其进行表征评价.结果表明,通过单因素试验确定的三因素分别是:膜材比、脂质浓度和DMG-PEG 2000含量.三因素的三水平分别为:膜材比选择1∶1、2∶1、3∶1,脂质浓度选择15、20、25mmol/L,DMG-PEG2000含量选择5％、7％、9％.通过Box-Benhnken响应面分析法得出:当脂质纳米颗粒的膜材比为2∶1,脂质浓度为20 mmol/L,DMG-PEG2000含量为7％时,其脂质纳米颗粒的包封率为(94.8±0.15)％,粒径为(43.77±0.25)nm,聚合物分散指数(polymer dispersity index,PD1)为(0.14±0.04),Zeta 电位为(-0.44±0.15)mV.利用透射电镜观察该脂质纳米颗粒的形态为球形结构、分散均匀.稳定性试验显示4 ℃放置28 d,脂质纳米颗粒的平均粒径、PDI和包封率无显著变化,说明该脂质纳米颗粒稳定性良好.本研究为制备一种高效的脂质纳米颗粒提供了参考依据.
Abstract
Lipid nanoparticles are one of the most promising drug carriers for application.To address the impact of raw material formulation on the self-assembly of lipid nanoparticles,the study aims to optimize its formulation.The encapsulation efficiency was used as the evaluation index,the film-material ratio,lipid concentration,and the content of DMG-PEG 2000 were determined by single factor experiments.Box-Benhnken response surface analysis was used to optimize the preparation process of lipid nanoparticles,and their characterization was evaluated.The results showed that the three factors film-material ratio,lipid concentration and DMG-PEG 2000 content were determined by single factor experiments.The three levels of the three factors were:film-material material ratio was selected as 1∶1 and 2∶1,3∶1,lipid concentration was selected as 15,20 and 25 mmol/L,and DMG-PEG2000 content was selected as 5％,7％and 9％.The results are obtained by Box-Benhnken response surface analysis.When the film-material ratio of lipid nanoparticles was 2∶1,the concentration of lipid was 20mmol/L,and the content of DMG-PEG2000 was 7％,the encapsulation efficiency of lipid nanoparticles was(94.8±0.15)％,the particle size was(43.77±0.25)nm,polymer dispersity index(PDI)was(0.14±0.04),Zeta potential was(-0.44±0.15)mV,and the shape of the lipid nanoparticle is spherical and uniformly dispersed by transmission electron microscop.The stability test showed that after being placed at 4 ℃ for 28 days,there is no significant change in the average particle size,PDI and encapsulation efficiency of the lipid nanoparticles,indicating good stability of the lipid nanoparticles.This study provides a reference basis for the preparation of an efficient lipid nanoparticle.
关键词
脂质纳米颗粒/Box-Benhnken响应面法/单因素/包封率Key words
lipid nanoparticles/Box-Benhnken response surface method/single factor/encapsula-tion efficiency引用本文复制引用
基金项目
国家重点研发计划项目(2022YFD1800603)
国家重点研发计划项目(2021YFD1800300)
国家自然科学基金项目(32072859)
国家自然科学基金项目(32072847)
国家自然科学基金项目(32002272)
国家自然科学基金青年基金项目(32301127)
2023兰州市人才创业创新项目(2023-RC-3)
出版年
2024
国家科技期刊平台
NSTL
万方数据