Pharmaceutical Research ( IF 3.7 ) Pub Date : 2021-05-17 , DOI: 10.1007/s11095-021-03056-2 Eva C Arrua 1 , Olga Hartwig 2, 3 , Duy-Khiet Ho 2 , Brigitta Loretz 2 , Xabier Murgia 2 , Claudio J Salomon 1, 4 , Claus-Michael Lehr 2, 3
Purpose
The aim of this work was to formulate and characterize surfactant-free glibenclamide nanoparticles using Eudragit RLPO and polyethylene glycol as sole stabilizer.
Methods
Glibenclamide nanoparticles were obtained by nanoprecipitation and evaluated in terms of drug content, encapsulation efficiency, apparent saturation solubility, drug release profile, solid state and storage stability. The influence of different stirring speed on the particle size, size distribution and zeta potential of the nanoparticles was investigated. The nanoparticle biocompatibility and permeability were analyzed in vitro on Caco-2 cell line (clone HTB-37) and its interaction with mucin was also investigated.
Results
It was found that increasing the molecular weight of polyethylene glycol from 400 to 6000 decreased drug encapsulation, whereas the aqueous solubility and dissolution rate of the drug increased. Particle size of the nanoformulations, with and without polyethylene glycol, were between 140 and 460 nm. Stability studies confirmed that glibenclamide nanoparticles were stable, in terms of particle size, after 120 days at 4°C. In vitro studies indicated minimal interactions of glibenclamide nanoparticles and mucin glycoproteins suggesting favorable properties to address the intestinal mucus barrier. Cell viability studies confirmed the safety profile of these nanoparticles and showed an increased permeation through epithelial cells.
Conclusion
Taking into consideration these findings, polyethylene glycol is a useful polymer for stabilizing these surfactant-free glibenclamide nanoparticles and represent a promising alternative to improve the treatment of non-insulin dependent diabetes.
中文翻译:
不含表面活性剂的格列本脲纳米颗粒:与生物屏障相互作用的配方、表征和评估
目的
这项工作的目的是使用 Eudragit RLPO 和聚乙二醇作为唯一稳定剂来配制和表征不含表面活性剂的格列本脲纳米颗粒。
方法
通过纳米沉淀获得格列本脲纳米颗粒,并在药物含量、包封率、表观饱和溶解度、药物释放曲线、固态和储存稳定性方面进行评估。研究了不同搅拌速度对纳米颗粒粒径、粒径分布和zeta电位的影响。在 Caco-2 细胞系(克隆 HTB-37)上体外分析了纳米颗粒的生物相容性和渗透性,并研究了它与粘蛋白的相互作用。
结果
发现将聚乙二醇的分子量从 400 增加到 6000 会降低药物的包封率,而药物的水溶性和溶出率会增加。含和不含聚乙二醇的纳米制剂的粒径在 140 和 460 nm 之间。稳定性研究证实,格列本脲纳米颗粒在 4°C 下 120 天后在粒径方面是稳定的。体外研究表明格列本脲纳米颗粒和粘蛋白糖蛋白的相互作用最小,表明其具有解决肠道粘液屏障的有利特性。细胞活力研究证实了这些纳米颗粒的安全性,并显示通过上皮细胞的渗透增加。
结论
考虑到这些发现,聚乙二醇是一种有用的聚合物,可用于稳定这些不含表面活性剂的格列本脲纳米颗粒,是改善非胰岛素依赖型糖尿病治疗的有前景的替代方案。