Pizzol Carine Dal, Filippin-Monteiro Fabíola Branco, Restrepo Jelver Alexander Sierra, Pittella Frederico, Silva Adny Henrique, Alves de Souza Paula, Machado de Campos Angela, Creczynski-Pasa Tânia Beatriz
Departamento de Ciências Farmacêuticas, Programa de Pós-Graduação em Farmácia, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.
Progama de Pós-Graduação em Engenharia de Materiais, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.
Int J Environ Res Public Health. 2014 Aug 20;11(8):8581-96. doi: 10.3390/ijerph110808581.
Nine types of solid lipid nanoparticle (SLN) formulations were produced using tripalmitin (TPM), glyceryl monostearate (GM) or stearic acid (SA), stabilized with lecithin S75 and polysorbate 80. Formulations were prepared presenting PI values within 0.25 to 0.30, and the physicochemical properties, stability upon storage and biocompatibility were evaluated. The average particle size ranged from 116 to 306 nm, with a negative surface charge around -11 mV. SLN presented good stability up to 60 days. The SLN manufactured using SA could not be measured by DLS due to the reflective feature of this formulation. However, TEM images revealed that SA nanoparticles presented square/rod shapes with an approximate size of 100 nm. Regarding biocompatibility aspects, SA nanoparticles showed toxicity in fibroblasts, causing cell death, and produced high hemolytic rates, indicating toxicity to red blood cells. This finding might be related to lipid type, as well as, the shape of the nanoparticles. No morphological alterations and hemolytic effects were observed in cells incubated with SLN containing TPM and GM. The SLN containing TPM and GM showed long-term stability, suggesting good shelf-life. The results indicate high toxicity of SLN prepared with SA, and strongly suggest that the components of the formulation should be analyzed in combination rather than separately to avoid misinterpretation of the results.
使用三棕榈酸甘油酯(TPM)、单硬脂酸甘油酯(GM)或硬脂酸(SA),以卵磷脂S75和聚山梨酯80为稳定剂,制备了九种固体脂质纳米粒(SLN)制剂。制备的制剂的PI值在0.25至0.30之间,并对其理化性质、储存稳定性和生物相容性进行了评估。平均粒径范围为116至306 nm,表面电荷为负,约为 -11 mV。SLN在长达60天内表现出良好的稳定性。由于该制剂具有反射特性,使用SA制备的SLN无法通过动态光散射(DLS)测量。然而,透射电子显微镜(TEM)图像显示,SA纳米粒呈现方形/棒状,尺寸约为100 nm。关于生物相容性方面,SA纳米粒在成纤维细胞中显示出毒性,导致细胞死亡,并产生高溶血率,表明对红细胞有毒性。这一发现可能与脂质类型以及纳米粒的形状有关。在用含有TPM和GM的SLN孵育的细胞中未观察到形态学改变和溶血效应。含有TPM和GM的SLN显示出长期稳定性,表明保质期良好。结果表明用SA制备的SLN具有高毒性,并强烈建议应综合分析制剂的成分,而不是单独分析,以避免对结果的误解。