Hebar Alexandra, Koller Christiane, Seifert Jan-Marcus, Chabicovsky Monika, Bodenteich Angelika, Bernkop-Schnürch Andreas, Grassauer Andreas, Prieschl-Grassauer Eva
MC Toxicology Consulting GmbH, Vienna, Austria.
Marinomed Biotechnologie GmbH, Vienna, Austria.
PLoS One. 2015 Apr 13;10(4):e0122911. doi: 10.1371/journal.pone.0122911. eCollection 2015.
Carrageenan has been widely used as food additive for decades and therefore, an extended oral data set is available in the public domain. Less data are available for other routes of administration, especially intranasal administration. The current publication describes the non-clinical safety and toxicity of native (non-degraded) iota-carrageenan when applied intranasally or via inhalation. Intranasally applied iota-carrageenan is a topically applied, locally acting compound with no need of systemic bioavailability for the drug's action. Animal experiments included repeated dose local tolerance and toxicity studies with intranasally applied 0.12% iota-carrageenan for 7 or 28 days in New Zealand White rabbits and nebulized 0.12% iota-carrageenan administered to F344 rats for 7 days. Permeation studies revealed no penetration of iota-carrageenan across nasal mucosa, demonstrating that iota-carrageenan does not reach the blood stream. Consistent with this, no relevant toxic or secondary pharmacological effects due to systemic exposure were observed in the rabbit or rat repeated dose toxicity studies. Data do not provide any evidence for local intolerance or toxicity, when carrageenan is applied intranasally or by inhalation. No signs for immunogenicity or immunotoxicity have been observed in the in vivo studies. This is substantiated by in vitro assays showing no stimulation of a panel of pro-inflammatory cytokines by iota-carrageenan. In conclusion, 0.12% iota-carrageenan is safe for clinical use via intranasal application.
几十年来，角叉菜胶一直被广泛用作食品添加剂，因此，在公共领域有大量的口服数据集。关于其他给药途径的数据较少，尤其是鼻内给药。本出版物描述了天然（未降解）ι-角叉菜胶经鼻内或吸入给药时的非临床安全性和毒性。经鼻内应用的ι-角叉菜胶是一种局部应用、局部起作用的化合物，药物作用无需全身生物利用度。动物实验包括在新西兰白兔中用0.12%ι-角叉菜胶经鼻内给药7天或28天的重复剂量局部耐受性和毒性研究，以及在F344大鼠中雾化吸入0.12%ι-角叉菜胶7天。渗透研究表明，ι-角叉菜胶不会穿过鼻黏膜，这表明ι-角叉菜胶不会进入血流。与此一致的是，在兔子或大鼠的重复剂量毒性研究中未观察到因全身暴露引起的相关毒性或次要药理作用。当角叉菜胶经鼻内或吸入给药时，数据未提供任何局部不耐受或毒性的证据。在体内研究中未观察到免疫原性或免疫毒性的迹象。体外试验表明，ι-角叉菜胶不会刺激一组促炎细胞因子，这证实了上述结论。总之，0.12%ι-角叉菜胶经鼻内应用临床使用是安全的。
