Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 52, Josef Möller Haus, 6020 Innsbruck, Austria.
Toxicol In Vitro. 2012 Feb;26(1):150-6. doi: 10.1016/j.tiv.2011.10.011. Epub 2011 Oct 26.
The purpose of this study was to determine the concentration-dependent effect of selected solubilizers, used in common nasal drug formulations, on ciliary beat frequency (CBF) in human nasal epithelial cell cultures. CBF was measured by a high-speed digital imaging method. Excised ciliated human nasal epithelial cells were incubated for 60min with the solubilizers and determination of the half maximal inhibitory concentration (IC(50)), followed by a reversibility test. LDH test was performed on human nasal epithelial cells with the solubilizing agents. These were applied to nasal epithelial cells in IC(50) values. The following rank order in IC(50) values was obtained for the solubilizers: glycerol>propylene glycol>polyethylene glycol 300>N,N-dimethylacetamide>polyethylene glycol 400>ethanol>ethylendiamindihydrochloride>polyvinylpyrrolidon 25>polyvinylpyrrolidon 90. The highest reversibility of approximately 75% was shown by propylene glycol and polyethylene glycol 300 at a concentration of 30% (v/v). Results from the LDH test showed that N,N-dimethylacetamide displayed the highest cytotoxicity with 5.2% at a concentration of 14.5% (v/v). According to these results, several solubilizers can alter the CBF frequency and thus, have an impact on the nasal mucosa. Therefore, CBF studies with solubilizers used at a concentration relevant for nasal formulations are essential in the design of efficient and most notably safe nasal medicinal products.
本研究旨在确定常用鼻用制剂中几种增溶剂的浓度依赖性对人鼻腔上皮细胞纤毛摆动频率（CBF）的影响。采用高速数字成像法测量 CBF。将离体的纤毛人鼻腔上皮细胞与增溶剂孵育 60min，测定半抑制浓度（IC（50）），然后进行可逆性试验。用人鼻腔上皮细胞的 LDH 试验测定增溶剂。将增溶剂以 IC（50）值应用于鼻上皮细胞。增溶剂的 IC（50）值依次为：甘油＞丙二醇＞聚乙二醇 300＞N，N-二甲基乙酰胺＞聚乙二醇 400＞乙醇＞乙二胺二盐酸盐＞聚乙烯吡咯烷酮 25＞聚乙烯吡咯烷酮 90。丙二醇和聚乙二醇 300 在 30%（v/v）浓度下的可逆性最高，约为 75%。LDH 试验结果表明，N，N-二甲基乙酰胺在 14.5%（v/v）浓度下的细胞毒性最高，为 5.2%。根据这些结果，几种增溶剂可以改变 CBF 频率，从而对鼻黏膜产生影响。因此，在设计高效且尤其是安全的鼻用药物时，使用与鼻用制剂浓度相关的增溶剂进行 CBF 研究至关重要。
