Department of Biochemistry and Molecular Biology, Faculty of Biology, and Research Institute "Hospital 12 de Octubre (imas12)", Universidad Complutense, 28040, Madrid, Spain.
Charité-Universitätsmedizin Berlin, Institut für funktionelle Anatomie, Campus Mitte, Philippstrasse 12, 10115, Berlin, Germany.
Sci Rep. 2020 Jan 28;10(1):1385. doi: 10.1038/s41598-020-58248-4.
CHF5633 is a novel synthetic clinical pulmonary surfactant preparation composed by two phospholipid species, dipalmitoyl phosphatidylcholine (DPPC) and palmitoyloleoyl phosphatidylglycerol (POPG), and synthetic analogues of the hydrophobic surfactant proteins SP-B and SP-C. In this study, the interfacial properties of CHF5633 in the absence and in the presence of inhibitory serum proteins have been assessed in comparison with a native surfactant purified from porcine lungs and with poractant alpha, a widely used clinical surfactant preparation. The study of the spreading properties of CHF5633 in a Wilhelmy balance, its ability to adsorb and accumulate at air-liquid interfaces as revealed by a multiwell fluorescence assay, and its dynamic behavior under breathing-like compression-expansion cycling in a Captive Bubble Surfactometer (CBS), all revealed that CHF5633 exhibits a good behavior to reduce and sustain surface tensions to values below 5 mN/m. CHF5633 shows somehow slower initial interfacial adsorption than native surfactant or poractant alpha, but a better resistance to inhibition by serum proteins than the animal-derived clinical surfactant, comparable to that of the full native surfactant complex. Interfacial CHF5633 films formed in a Langmuir-Blodgett balance coupled with epifluorescence microscopy revealed similar propensity to segregate condensed lipid domains under compression than films made by native porcine surfactant or poractant alpha. This ability of CHF5633 to segregate condensed lipid phases can be related with a marked thermotropic transition from ordered to disordered membrane phases as exhibited by differential scanning calorimetry (DSC) of CHF5633 suspensions, occurring at similar temperatures but with higher associated enthalpy than that shown by poractant alpha. The good interfacial behavior of CHF5633 tested under physiologically meaningful conditions in vitro and its higher resistance to inactivation by serum proteins, together with its standardized and well-defined composition, makes it a particularly useful therapeutic preparation to be applied in situations associated with lung inflammation and edema, alone or in combined strategies to exploit surfactant-facilitated drug delivery.
CHF5633 是一种新型的合成临床肺表面活性剂制剂，由两种磷脂组成，二棕榈酰磷脂酰胆碱（DPPC）和棕榈酰油酰基磷脂酰甘油（POPG），以及人工合成的疏水表面活性蛋白 SP-B 和 SP-C 的类似物。在这项研究中，评估了 CHF5633 在不存在和存在抑制性血清蛋白的情况下的界面特性，并与从猪肺中纯化的天然表面活性剂以及广泛使用的临床表面活性剂制剂 poractant alpha 进行了比较。通过威比尔天平研究 CHF5633 的铺展特性，通过多孔荧光测定法研究其在气液界面上的吸附和积累能力，以及在 Captive Bubble Surfactometer（CBS）中进行类似呼吸的压缩-膨胀循环下的动态行为，所有这些都表明 CHF5633 具有降低和维持表面张力至 5 mN/m 以下的良好性能。CHF5633 的初始界面吸附速度比天然表面活性剂或 poractant alpha 稍慢，但对血清蛋白抑制的抵抗力优于动物源性临床表面活性剂，与完整的天然表面活性剂复合物相当。与天然猪肺表面活性剂或 poractant alpha 相比，Langmuir-Blodgett 天平与荧光显微镜耦合形成的界面 CHF5633 薄膜在压缩下具有相似的分离浓缩脂质域的倾向。CHF5633 分离浓缩脂质相的能力可能与其明显的热致从有序到无序膜相的转变有关，通过差示扫描量热法（DSC）测定 CHF5633 悬浮液的相变，在相似的温度下，但具有比 poractant alpha 更高的相关焓。CHF5633 在体外具有生理相关条件下的良好界面性能，以及对血清蛋白失活的更高抵抗力，再加上其标准化和明确的组成，使其成为一种特别有用的治疗制剂，可单独或结合利用表面活性剂促进药物传递的策略，应用于与肺部炎症和水肿相关的情况。
