Pharmaceutical Technology and Biopharmacy, Institute of Pharmacy, Friedrich Schiller University Jena, Lessingstraße 8, 07743 Jena, Germany.
Leibniz Institute of Photonic Technology, Albert-Einstein-Str. 9, 07745 Jena, Germany; Center for Sepsis Control and Care, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany.
Int J Pharm. 2021 Apr 15;599:120404. doi: 10.1016/j.ijpharm.2021.120404. Epub 2021 Feb 26.
In the present study, the anti-inflammatory lipophilic drug atorvastatin was encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) using a sustainable method in comparison to the standard emulsion-diffusion-evaporation technique. For the sustainable method the organic solvent ethyl acetate was fully replaced by 400 g/mol poly(ethylene glycol) (PEG 400). Both techniques led to the formation of nanoparticles with comparable sizes of about 170 to 247 nm depending on the polymer type, with monomodal size distribution and negative zeta potential. All nanoparticles demonstrated a high biocompatibility in a shell-less hen's egg model and displayed an anti-inflammatory effect in human monocytes. The use of PEG 400 resulted in plasticizing effects and a lower crystallinity of the PLGA nanoparticles as determined by differential scanning calorimetry and Raman spectroscopy, which correlated with a faster drug release. Interestingly, the particles prepared by the sustainable method showed a crystallinity and drug release kinetics similar to nanoparticles made of PEG-PLGA using the standard method. Conclusively, the sustainable method is a fast and easy to perform technique suitable to prepare atorvastatin-loaded PLGA nanoparticles avoiding toxic and environmentally damaging drawbacks frequently associated with classical organic solvents.
在本研究中,与标准的乳液扩散蒸发技术相比,采用可持续的方法将抗炎亲脂性药物阿托伐他汀包封在聚(D,L-丙交酯-共-乙交酯)(PLGA)中。对于可持续的方法,将有机溶剂乙酸乙酯完全用 400 g/mol 的聚乙二醇(PEG 400)代替。两种技术都导致纳米粒子的形成,其大小相当,约为 170 至 247 nm,取决于聚合物类型,具有单模态的粒径分布和负的zeta 电位。所有纳米粒子在无壳鸡蛋模型中均显示出高生物相容性,并在人单核细胞中显示出抗炎作用。使用 PEG 400 会导致 PLGA 纳米粒子的增塑作用和结晶度降低,这可以通过差示扫描量热法和拉曼光谱法来确定,这与药物释放速度的加快有关。有趣的是,通过可持续方法制备的颗粒显示出与使用标准方法制备的 PEG-PLGA 纳米颗粒相似的结晶度和药物释放动力学。总之,可持续方法是一种快速且易于实施的技术,适用于制备阿托伐他汀负载的 PLGA 纳米粒子,避免了与经典有机溶剂相关的有毒和对环境有害的缺点。