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

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、25 mmol/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,PDI)为(0.14±0.04),Zeta电位为(-0.44±0.15)m V。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。

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 C 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.