Correlation between epithelial toxicity and surfactant structure as derived from the effects of polyethyleneoxide surfactants on Caco-2 cell monolayers and pig nasal mucosa
Correlation between epithelial toxicity and surfactant structure as derived from the effects of polyethyleneoxide surfactants on Caco-2 cell monolayers and pig nasal mucosa
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DOI：
10.1002/jps.20283
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发表时间：
2005-04-01
影响因子：
3.8
通讯作者：
Johansson, F
中科院分区：
文献类型：
--
作者：
Ekelund, K;Östh, K;Johansson, F
通过两种体外模型，即安装在水平Ussing室中的猪鼻粘膜和Caco-2单层细胞，研究了非离子表面活性剂的细胞毒性作用。筛选了一系列具有广泛亲水头基尺寸和疏水链长度的同源聚环氧乙烷 (PEO) 表面活性剂，以观察其对跨上皮电阻 (TEER) 和跨 Caco-2 细胞单层的甘露醇渗透性的浓度依赖性影响。表面活性剂浓度增加时对渗透性的影响趋势与对 TEER 的影响一致。表面活性剂分子结构与细胞毒性的相关性表明，PEO 基团的大小是比烃链大小更关键的参数。更具体地说，发现非常长的 PEO 基团（> 30 个 EO 单位）的存在会导致细胞毒性降低。在研究 PEO 表面活性剂对安装在水平 Ussing 室中的猪鼻粘膜的影响时也观察到类似的趋势。然而，鼻粘膜比 Caco-2 细胞对高表面活性剂浓度的耐受性更高。从胶束表面吸附和胶束增溶的角度讨论了表面活性剂分子结构与细胞毒性作用之间的关系。在两种不同的表面活性剂浓度（0.01 和 1 mg/mL）下研究了表面活性剂对布地奈德溶解度的影响。在较低浓度下，所有表面活性剂的增溶能力都很有限，并且增溶能力与 cmc 之间不存在相关性。另一方面，在较高浓度下，所有表面活性剂都显着增加了布地奈德的溶解度。发现头基具有 40 个 EO 单元的 C-18 PEO-酯是布地奈德的有效胶束增溶剂，不会对 Caco-2 细胞单层造成不利影响。 (c) 2005 年 Wiley-Liss, Inc.
The cell toxic effects of nonionic surfactants were investigated by means of two in vitro models, namely pig nasal mucosa mounted in horizontal Ussing chambers, and Caco-2 cell monolayers. A series of homologous polyethyleneoxide (PEO) surfactants with a wide span in hydrophilic head-group size and hydrophobic chain lengths were screened for concentration-dependent effects on the transepithelial electrical resistance (TEER) and mannitol permeability across Caco-2 cell monolayers. Trends in effects on permeability in the presence of increasing surfactant concentration coincided with the effects seen on TEER. Correlation of surfactant molecular structure with cell toxicity showed the size of the PEO group to be a more critical parameter than the size of the hydrocarbon chain. More specifically, the presence of very long PEO groups (> 30 EO units) were found to lead to a decrease in cell toxicity. Similar trends were observed in the studies of the effects of PEO surfactants on pig nasal mucosa mounted in horizontal Ussing chambers. However, the nasal mucosa was somewhat more tolerant towards high surfactant concentrations than the Caco-2 cells. The relation between surfactant molecular structure and cell toxic effects is discussed in terms of micellar surface adsorption and micellar solubilization. The effect of the surfactants on the solubility of budesonide was investigated at two different surfactant concentrations (0.01 and 1 mg/mL). At the lower concentration, the solubilizing capacity of all of the surfactants was marginal, and there was no correlation between solubilizing capacity and cmc. At the higher concentration, on the other hand, all surfactants substantially increased the solubility of budesonide. The C-18 PEO-ester with 40 EO units in the head group was found to be an efficient micellar solubilizer for budesonide, without causing adverse effects on the Caco-2 cell monolayers. (c) 2005 Wiley-Liss, Inc.