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采用受限液滴表面张力法对临床用表面活性剂进行比较生物物理研究。

Comparative biophysical study of clinical surfactants using constrained drop surfactometry.

机构信息

Department of Mechanical Engineering, University of Hawaii at Manoa, Honolulu, Hawaii, United States.

Department of Pediatrics, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, United States.

出版信息

Am J Physiol Lung Cell Mol Physiol. 2024 Oct 1;327(4):L535-L546. doi: 10.1152/ajplung.00058.2024. Epub 2024 Aug 19.

Abstract

Surfactant replacement therapy is crucial in managing neonatal respiratory distress syndrome (RDS). Currently licensed clinical surfactants in the United States and Europe, including Survanta, Infasurf, Curosurf, and Alveofact, are all derived from bovine or porcine sources. We conducted a comprehensive examination of the biophysical properties of these four clinical surfactant preparations under physiologically relevant conditions, using constrained drop surfactometry (CDS). The assessed biophysical properties included the adsorption rate, quasi-static and dynamic surface activity, resistance to surfactant inhibition by meconium, and the morphology of the adsorbed surfactant films. This comparative study unveiled distinct in vitro biophysical properties of these clinical surfactants and revealed correlations between their chemical composition, lateral film structure, and biophysical functionality. Notably, at 1 mg/mL, Survanta exhibited a significantly lower adsorption rate compared with the other preparations at the same surfactant concentration. At 10 mg/mL, Infasurf, Curosurf, and Survanta all demonstrated excellent dynamic surface activity, whereas Alveofact exhibited the poorest quasi-static and dynamic surface activity. The suboptimal surface activity of Alveofact is found to be correlated with its unique monolayer-predominant morphology, in contrast to other surfactants forming multilayers. Curosurf, in particular, showcased superior resistance to biophysical inhibition by meconium compared with other preparations. Understanding the diverse biophysical behaviors of clinical surfactants provides crucial insights for precision and personalized design in treating RDS and other respiratory conditions. The findings from this study contribute valuable perspectives for the development of more efficacious and fully synthetic surfactant preparations. A thorough investigation into the biophysical properties of four animal-derived clinical surfactant preparations was conducted through constrained drop surfactometry under physiologically relevant conditions. This comparative study unveiled unique in vitro biophysical characteristics among these clinical surfactants, establishing correlations between their chemical composition, lateral film structure, and biophysical functionality. The acquired knowledge offers essential insights for the precise and personalized design of clinical surfactant for the treatment of respiratory distress syndrome and other respiratory conditions.

摘要

表面活性剂替代疗法在治疗新生儿呼吸窘迫综合征(RDS)中至关重要。目前在美国和欧洲获得许可的临床用表面活性剂,包括固尔苏、珂立苏、沐舒坦和猪肺磷脂,均来源于牛或猪源。我们使用受限滴表面张力法(CDS),在生理相关条件下,对这四种临床用表面活性剂制剂的生物物理特性进行了全面评估。评估的生物物理特性包括吸附速率、准静态和动态表面活性、对胎粪抑制表面活性剂活性的抵抗力以及吸附表面活性剂膜的形态。这项比较研究揭示了这些临床用表面活性剂的独特体外生物物理特性,并揭示了它们的化学成分、横向膜结构和生物物理功能之间的相关性。值得注意的是,在 1mg/ml 浓度下,固尔苏的吸附速率明显低于其他制剂。在 10mg/ml 浓度下,珂立苏、沐舒坦和固尔苏均表现出极好的动态表面活性,而猪肺磷脂表现出最差的准静态和动态表面活性。猪肺磷脂的表面活性不理想被发现与其独特的以单层为主的形态有关,而其他表面活性剂则形成多层。与其他制剂相比,固尔苏对胎粪的生物物理抑制具有更好的抵抗力。了解临床用表面活性剂的不同生物物理行为为治疗 RDS 和其他呼吸状况的精确和个性化设计提供了关键见解。本研究的结果为开发更有效和完全合成的表面活性剂制剂提供了有价值的视角。通过在生理相关条件下使用受限滴表面张力法对四种动物源临床用表面活性剂制剂的生物物理特性进行了全面研究。这项比较研究揭示了这些临床用表面活性剂之间独特的体外生物物理特性,建立了它们的化学成分、横向膜结构和生物物理功能之间的相关性。获得的知识为治疗呼吸窘迫综合征和其他呼吸状况的临床用表面活性剂的精确和个性化设计提供了重要的见解。

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