Department of Biophysical Chemistry, Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan.
Langmuir. 2010 Dec 7;26(23):18256-65. doi: 10.1021/la103118d. Epub 2010 Nov 4.
Effective additives to pulmonary surfactant (PS) preparations for therapy of respiratory distress syndrome (RDS) are being intensively sought. We report here the investigation of the effects of partially fluorinated amphiphiles (PFA) on the surface behavior of a model PS formulation. When small amounts of a partially fluorinated alcohol C(8)F(17)C(m)H(2m)OH (F8HmOH, m = 5 and 11) are added to the PS model preparation (a dipalmitoylphosphatidylcholine (DPPC)/Hel 13-5 peptide mixture) considered here, the effectiveness of the latter in in vitro pulmonary functions is enhanced. The mechanism for the improved efficacy depends on the hydrophobic chain length of the added PFA molecules. The shorter PFA, F8H5OH, when incorporated in the monolayer of the PS model preparation, promotes a disordered liquid-expanded (LE) phase upon lateral compression (fluidization). In contrast, the addition of the longer PFA, F8H11OH, reduces the disordered LE/ordered liquid-condensed (LC) phase transition pressure and promotes the growth of ordered domains (solidification). Furthermore, compression-expansion cycles suggest that F8H5OH, when incorporated in the PS model preparation, undergoes an irreversible elimination into the subphase, whereas F8H11OH enhances the squeeze-out phenomenon of the SP-B mimicking peptide, which is important in pulmonary functions and is related to the formation of a solid-like monolayer at the surface and of a surface reservoir just below the surface. F8H11OH particularly reinforces the effectiveness of DPPC in terms of minimum reachable surface tension, and of preservation of the integrated hysteresis area between compression and expansion isotherms, the two latter parameters being generally accepted indices for assessing PS efficacy. We suggest that PFA amphiphiles may be useful potential additives for synthetic PS preparations destined for treatment of RDS in premature infants and in adults.
目前正在积极寻找可添加至肺表面活性剂（PS）制剂以治疗呼吸窘迫综合征（RDS）的有效添加剂。我们在此报告了对部分氟化两亲物（PFA）对模型 PS 制剂表面行为影响的研究。当向此处考虑的 PS 模型制剂（二棕榈酰磷脂酰胆碱（DPPC）/Hel 13-5 肽混合物）中添加少量部分氟化醇 C(8)F(17)C(m)H(2m)OH（F8HmOH，m = 5 和 11）时，后者在体外肺功能中的有效性会得到增强。这种增效作用的机制取决于添加的 PFA 分子的疏水性链长。较短的 PFA，F8H5OH，当掺入 PS 模型制剂的单层中时，在横向压缩（流化）时会促进无序的扩展（LE）相。相反，较长的 PFA，F8H11OH 的添加会降低无序的 LE/有序液体凝聚（LC）相转变压力，并促进有序畴（凝固）的生长。此外，压缩-膨胀循环表明，F8H5OH 在掺入 PS 模型制剂时会不可逆地消除到亚相中，而 F8H11OH 增强了类似于 SP-B 的模拟肽的挤出现象，这在肺功能中很重要，与表面下形成固态单层和表面储库有关。F8H11OH 特别增强了 DPPC 在可达到的最小表面张力以及压缩和膨胀等温线之间积分滞后面积的保留方面的有效性，这两个后两个参数通常被用作评估 PS 功效的指标。我们认为 PFA 两亲物可能是用于治疗早产儿和成人 RDS 的合成 PS 制剂的潜在有用添加剂。
