Nakahara Hiromichi
Department of Biophysical Chemistry, Graduate School of Pharmaceutical Sciences, Nagasaki International University.
J Oleo Sci. 2016;65(2):99-109. doi: 10.5650/jos.ess15222.
Pulmonary surfactant (PS) preparations based mainly on bovine or porcine extracts are commonly administered to patients with neonatal respiratory distress syndrome (NRDS) for therapy. The preparations are sufficiently effective to treat NRDS; however, they are associated with a risk of infection and involve costly purification procedures to achieve batch-to-batch reproducibility. Therefore, we investigated the mechanism and interfacial behavior of synthetic PS preparations containing a mimicking peptide (KLLKLLLKLWLKLLKLLL, Hel 13-5). In particular, a hybrid PS formulation with fluorinated amphiphiles is reported from the perspective of surface chemistry. Fluorinated amphiphiles are characterized by exceptional chemical and biological inertness, high oxygen-dissolving capacity, low surface tension, excellent spreading ability, and high fluidity. These properties are superior to those for the corresponding hydrocarbon analogs. Indeed, a small amount of fluorinated long-chain alcohols enhances the effectiveness of the model PS preparation for in vitro pulmonary functions. Moreover, the mode of the improved efficacy differs depending on the hydrophobic chain length in the alcohols. For alcohols with a short fluorocarbon (FC) chain, the monolayer phase of the model PS preparation remains disordered (fluidization). However, the addition of alcohols containing a long FC chain reduces the disordered/ordered phase transition pressure and the growth of ordered domains of the monolayer (condensation). Furthermore, repeated compression-expansion isotherms of the monolayers, which can simulate respiration in the lung, suggest irreversible elimination of the short-FC alcohol into the subphase and enhancement of the squeeze-out phenomenon of certain PS components by solid-like monolayer formation induced by the long-FC alcohol. We demonstrated that fluorinated amphiphiles may be used as additives for synthetic or commercial PS preparations for RDS treatment.
主要基于牛或猪提取物的肺表面活性物质（PS）制剂通常用于治疗新生儿呼吸窘迫综合征（NRDS）患者。这些制剂治疗NRDS的效果足够显著；然而，它们存在感染风险，并且为实现批次间的可重复性需要昂贵的纯化程序。因此，我们研究了含有模拟肽（KLLKLLLKLWLKLLKLLL，Hel 13 - 5）的合成PS制剂的作用机制和界面行为。特别是，从表面化学的角度报道了一种含氟两亲物的混合PS制剂。含氟两亲物具有特殊的化学和生物惰性、高氧溶解能力、低表面张力、出色的铺展能力和高流动性。这些特性优于相应的烃类类似物。事实上，少量的含氟长链醇可提高模型PS制剂体外肺功能的有效性。此外，疗效改善的模式因醇类中疏水链长度的不同而有所差异。对于含短氟碳（FC）链的醇类，模型PS制剂的单分子层相保持无序状态（流化）。然而，添加含长FC链的醇类会降低单分子层无序/有序相转变压力以及单分子层有序域的生长（凝聚）。此外，可模拟肺呼吸的单分子层重复压缩 - 膨胀等温线表明，短FC醇不可逆地进入亚相，并且长FC醇诱导形成的类固体单分子层增强了某些PS成分的挤出现象。我们证明了含氟两亲物可作为添加剂用于合成或商业PS制剂以治疗RDS。
