Department of Physiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 4 Mala Hora St., 036 01, Martin, Slovakia,
Adv Exp Med Biol. 2015;839:31-9. doi: 10.1007/5584_2014_64.
Exogenous pulmonary surfactant is a potential delivery system for topical medications via the conducting airways. Due to the sensitivity to inactivation of surfactant, mutual interaction with the shipped drug should be evaluated. Little is known about the interactions between surfactant and antimicrobial drugs. The aim of the present study was to evaluate whether biophysical properties of animal-derived surfactants are modified by the bactericidal antibiotic rifampicin. An intracellular activity and a broad antimicrobiotic spectrum toward Gram-negative and Gram-positive bacteria make rifampicin an interesting substance against pulmonary infections. Curosurf® (porcine surfactant from minced lungs) and Survanta® (bovine surfactant extract) were diluted to 2.5-5.0 mg/ml of phospholipids in 0.9 % NaCl and rifampicin (RIF) was added at 1, 5, and 10 % (w/w). Minimum (γ(min)) and maximum (γ(max)) surface tension of a cyclically compressed bubble in the mixture was assessed with a pulsating bubble surfactometer. After 5 min, γ(min) of Survanta at a concentration of 3 mg/ml was significantly increased after addition of 5 and 10 % RIF (both p < 0.001). At 1 % RIF, the γ(min) of Survanta was ≈10 mN/m and this value was not significantly different to that of Survanta alone. The γ(min) of Curosurf at 3 mg/ml was increased with 10 % RIF (p < 0.001), but not with 1 and 5 %. At 5 mg/ml Survanta was inhibited by 10 % RIF (p < 0.05), while γ(min) of Curosurf was low (<5 mN/m) in all mixtures. In conclusion, Curosurf and Survanta interfere with RIF in a concentration-dependent manner. At the appropriate phospholipid concentration, especially porcine-derived surfactant is able to retain good surface activity when mixed with antibiotics.
外源性肺表面活性剂是通过传导气道将局部药物递送至肺部的潜在给药系统。由于表面活性剂对失活很敏感，因此应评估其与所输送药物的相互作用。目前对于表面活性剂与抗菌药物之间的相互作用知之甚少。本研究旨在评估杀菌抗生素利福平是否会改变动物源性肺表面活性剂的生物物理特性。利福平对革兰氏阴性和革兰氏阳性细菌具有细胞内活性和广泛的抗微生物谱，使其成为治疗肺部感染的一种有趣物质。Curosurf®（来自切碎的肺的猪肺表面活性剂）和 Survanta®（牛肺表面活性剂提取物）以 2.5-5.0mg/ml 的磷脂浓度在 0.9%NaCl 中稀释，并加入 1%、5%和 10%（w/w）的利福平（RIF）。使用脉动气泡表面张力仪评估周期性压缩气泡混合物中的最小（γ(min)）和最大（γ(max)）表面张力。在 3mg/ml 的浓度下，Survanta 中 5%和 10%RIF 添加后γ(min)显著增加（均 p<0.001）。在 1%RIF 时，Survanta 的γ(min)约为 10mN/m，与单独使用 Survanta 时没有显著差异。在 3mg/ml 的浓度下，Curosurf 中 10%RIF 使γ(min)增加（p<0.001），而 1%和 5%RIF 则没有。在 5mg/ml 时，10%RIF 抑制 Survanta（p<0.05），而 Curosurf 在所有混合物中的γ(min)均较低（<5mN/m）。总之，Curosurf 和 Survanta 以浓度依赖的方式与 RIF 相互干扰。在适当的磷脂浓度下，特别是猪源表面活性剂与抗生素混合时能够保持良好的表面活性。
