The physical state of lipid nanoparticles influences their effect on in vitro cell viability
The physical state of lipid nanoparticles influences their effect on in vitro cell viability
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DOI：
10.1016/j.ejpb.2011.03.022
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发表时间：
2011-09-01
影响因子：
4.9
通讯作者：
Bunjes, Heike
中科院分区：
文献类型：
--
作者：
Petersen, Silvia;Steiniger, Frank;Bunjes, Heike
尽管脂质纳米颗粒代表了有效的药物载体，但对于许多制剂来说，毒性数据很少。因此，在本研究中，使用MTT测定系统地研究了不同脂质纳米粒子对L929小鼠成纤维细胞的细胞活力的影响。该制剂由三肉豆蔻酸甘油酯、三硬脂酸甘油酯或肉豆蔻胆固醇酯组成，并用泊洛沙姆188、聚山梨醇酯80、聚乙烯醇或大豆磷脂和甘胆酸钠的混合物进行稳定。根据脂质和储存条件，纳米颗粒以不同的物理状态或晶体修饰制备，从而导致不同的颗粒形状。细胞活力很大程度上受到颗粒基质的物理状态的影响，其中结晶纳米颗粒导致比相应的液体或液晶颗粒更强烈的活力下降。对细胞活力的影响还与基质脂质、稳定剂的类型和颗粒形状有关。然而，结晶三硬脂酸酯的不同多晶型变体的不同形状颗粒的效果是相当的。泊洛沙姆 188 稳定颗粒造成的低活力可能与强细胞摄取相关，这一点通过共焦激光扫描显微镜进行了研究。 (C) 2011 Elsevier B.V. 保留所有权利。
Although lipid nanoparticles represent potent drug carriers, for many formulations toxicity data are rare. Thus, in this study, the effect of different lipid nanoparticles on the cell viability of L929 mouse fibroblasts was systematically investigated using the MTT assay. The formulations were composed of trimyristin, tristearin or cholesteryl myristate stabilized with poloxamer 188, polysorbate 80, polyvinyl alcohol or a blend of soybean phospholipid and sodium glycocholate. Depending on lipid and storage conditions, the nanoparticles were prepared in different physical states or crystal modifications leading to different particle shapes. The cell viability was influenced considerably by the physical state of the particle matrix with crystalline nanoparticles causing a stronger decrease in viability than the corresponding liquid or liquid crystalline particles. Effects on the cell viability were also related to the type of matrix lipid, stabilizer and the particle shape. However, the effects of differently shaped particles of different polymorphic modifications of crystalline tristearin were comparable. The low viability caused by poloxamer 188-stabilized particles could be correlated with a strong cell uptake which was investigated by confocal laser scanning microscopy. (C) 2011 Elsevier B.V. All rights reserved.