MENG Ya-fei, ZHANG Wei-ling, LI Tong-tong, et al. Evaluation of Nasal Mucosa Toxicity of Cremophor RH40 and Labrafil M 1944 CS[J]. Chinese journal of experimental traditional medical formulae, 2014, 20(20): 20-23.
DOI:
MENG Ya-fei, ZHANG Wei-ling, LI Tong-tong, et al. Evaluation of Nasal Mucosa Toxicity of Cremophor RH40 and Labrafil M 1944 CS[J]. Chinese journal of experimental traditional medical formulae, 2014, 20(20): 20-23. DOI: 10.13422/j.cnki.syfjx.2014200020.
Evaluation of Nasal Mucosa Toxicity of Cremophor RH40 and Labrafil M 1944 CS
目的:考察乙醇-油酸聚乙二醇甘油酯(labrafil M 1944 CS)和聚氧乙烯氢化蓖麻油40(cremophor RH40)的鼻黏膜毒性,探讨其在鼻腔给药系统中应用的可行性。方法:以山梨糖醇酐油酸酯(span-80)和聚山梨酯-80(tween-80)为参比,采用在体蟾蜍上腭模型,光学显微镜下观察纤毛持续运动时间,考察cremophor RH40和labrafil M 1944 CS的纤毛毒性作用;运用家兔血细胞溶血试验,考察cremophor RH40和labrafil M 1944 CS对细胞膜完整性的影响。结果:体积分数为1%时,4种表面活性剂对纤毛运动的影响顺序为cremophor RH40 < labrafil M 1944 CS < tween-80 < span-80;cremophor RH40的细胞膜毒性最小,tween-80和span-80次之,而labrafil M 1944 CS的影响最大;cremophor RH40对细胞膜完整性无影响用量为tween-80和span-80的15倍。结论:在一定体积分数下cremophor RH40的鼻黏膜毒性作用较小,可应用于鼻腔给药制剂的研制。
Abstract
Objective: Nasal mucosa toxicity of cremophor RH40 and labrafil M 1944 CS were investigated
in order to explore feasibility of their application in nasal drug delivery system. Method: Compared with span-80 and tween-80
safety of surfactant was evaluated by testing cilia movement of in situ toad palate model and hemolysis test of erythrocyte membrane in rabbits. Result: When concentrations of these four kinds of surfactants were 1%
their effect on cilia movement was in order of cremophor RH40 < labrafil M 1944 CS < tween-80 < span-80. By survey of toxic effects on cell membranes
cremophor RH40 had little cell membrane toxicity
tween-80 and span-80 had moderate cell membrane toxicity
but labrafil M 1944 CS had serious cell membrane toxicity.Dosage of cremophor RH40 that had no effect on integrity of cell membrane was 15 times the amount of tween-80 and span-80. Conclusion: Cremophor RH40 has little toxic effect on nasal mucosa under a certain range of concentration that can be applied in nasal drug delivery system.