Synthetic surfactants with SP‐B and SP‐C analogues to enable worldwide treatment of neonatal respiratory distress syndrome and other lung diseases

Abstract

Treatment of neonatal respiratory distress syndrome (RDS) using animal‐derived lung surfactant preparations has reduced the mortality of handling premature infants with RDS to a 50th of that in the 1960s. The supply of animal‐derived lung surfactants is limited and only a part of the preterm babies is treated. Thus, there is a need to develop well‐defined synthetic replicas based on key components of natural surfactant. A synthetic product that equals natural‐derived surfactants would enable cost‐efficient production and could also facilitate the development of the treatments of other lung diseases than neonatal RDS. Recently the first synthetic surfactant that contains analogues of the two hydrophobic surfactant proteins B (SP‐B) and SP‐C entered clinical trials for the treatment of neonatal RDS. The development of functional synthetic analogues of SP‐B and SP‐C, however, is considerably more challenging than anticipated 30 years ago when the first structural information of the native proteins became available. For SP‐B, a complex three‐dimensional dimeric structure stabilized by several disulphides has necessitated the design of miniaturized analogues. The main challenge for SP‐C has been the pronounced amyloid aggregation propensity of its transmembrane region. The development of a functional non‐aggregating SP‐C analogue that can be produced synthetically was achieved by designing the amyloidogenic native sequence so that it spontaneously forms a stable transmembrane α‐helix.

In Vitro Functional and Structural Characterization of A Synthetic Clinical Pulmonary Surfactant with Enhanced Resistance to Inhibition

“…Even if it does not adsorb at first instance as efficiently as other clinical surfactants from natural origin, it is capable of quickly spreading along the interface at clinical doses. Its synthetic and reproducible composition makes it a good candidate in the treatment of adults when high and multiple doses are needed, avoiding safety issues with the potential presence of pathogenic entities from animal origin, or possible allergenic reactions 30 . However, its maximal advantage is the stability of its dynamic properties even in the presence of serum, making it a potentially useful preparation in situations associated with inflammation and edema as well as for drug delivery therapies to patients with inflamed and injured lungs.…”

Neonatal Respiratory Distress Syndrome: Things to Consider and Ways to Manage

“…Lung surfactant is a mixture of phospholipids and some specific proteins secreted by epithelium of alveoli, which lines the small airways. It primarily reduces the surface tension of liquid presented in terminal air spaces [57]. Lack of pulmonary surfactant is the main result of NRDS; so, prescription of pulmonary surfactant can augment respiratory function and pulmonary compliance resulting in elevated oxyhemoglobin level [58][59][60][61].…”

Nanocarrier Lipid Composition Modulates the Impact of Pulmonary Surfactant Protein B (SP-B) on Cellular Delivery of siRNA

“…The protein fraction consists of two major classes of specialized surfactant proteins (SPs), i.e., the larger and hydrophilic SP-A and SP-D, as well as the smaller hydrophobic SP-B and SP-C [21,22]. PS has been extensively studied mainly because of its functional role in mammalian breathing [22,23]. In the context of inhalation therapy with nanomedicines, PS is primarily regarded as one of the extracellular barriers in the deep lung that needs to be overcome to gain access to underlying target cells upon inhalation therapy [21].…”

“…In the context of inhalation therapy with nanomedicines, PS is primarily regarded as one of the extracellular barriers in the deep lung that needs to be overcome to gain access to underlying target cells upon inhalation therapy [21]. Its current therapeutic use is limited to the treatment of respiratory distress syndrome in premature infants, where modified PS from animal origin (e.g., Curosurf ® ) is approved for so-called surfactant replacement therapy [23].…”