Function of sinapultide in respiratory distress syndrome

Introduction 

Sinapultide (also known as KL4 peptide) is a synthetic protein used to mimic human SP-B. Respiratory distress syndrome (RDS) is characterised by surfactant deficiency leading to higher surface tension at the alveolar surface, widespread atelectasis and decreased available surface area for gas exchange. Surfactant protein (SP) promotes the adsorption of phospholipids to reduce surface tension, while the hydrophobic protein SP-B has the strongest function. Sinapultide is usually used as a drug in the form of an aerosol into premature infants with dipalmitoyl phosphatidylcholine (DPPC).

Pharmacologic action

Pulmonary surfactant (PS) is synthesized and secreted by Ⅱ alveolar cells, mainly including proteins and phospholipids which play an important role in reducing surface tension. Sinapultide can promote the absorption and distribution of phospholipids to the liquid surface, thus reducing the surface tension, and restore the surface activity of these baby lung tissues. In addition, Neutrophils are immune cells, but too much of them can lead to increased lung surface tension and a host of problems. Studies have found that Sinapultide prevents lung injury by blocking the flow of neutrophils into the alveoli. In addition, in vitro experiments showed that Sinapultide reduced the migration of neutrophils at the level of endothelial cells.

Function

RDS is a leading cause of mortality and morbidity in preterm infants. Surfactant replacement therapy has been widely used to prevent and treat RDS in these newborns and has now become a standard of care. So far clinicians had limited options available in choosing between animal-derived surfactants with inherent disadvantages of being an animal product, or first generation synthetic products that performed less well owing to the absence of surfactant protein. Experiments show that Sinapultide is more safe and effective, and has led to a dramatic improvement in both survival and major morbidity adjustment to RDS.

Pharmacokinetics and metabolism

Sinapultide is a 21 amino acid polypeptide that binds to the lipid interface, but its structure depends on the lipid. Studies have shown that when Sinapultide is expressed in a membrane protein host, it can cross the phospholipid layer. In addition, Sinapultide cross-links with the phospholipid primordium, increases the lateral stability of the phospholipid monolayer, and is involved in Lamellar Body (LB) formation. It also contains SP-A, lecithin and calcium can promote Ⅱ alveolar epithelial cells which intake of lecithin capsule foam material.

References:

1. Qiu, Y., Chow, M. Y., Liang, W., Chung, W. W., Mak, J. C., & Lam, J. K. (2017). From Pulmonary Surfactant, Synthetic KL4 Peptide as Effective siRNA Delivery Vector for Pulmonary Delivery. Molecular pharmaceutics, 14 (12), 4606-4617.

2. Liu, D., Zhang, Z., Qin, Z., Xing, J., Liu, Y., Jin, J., ... & Gu, N. (2018). Sinapultide-loaded lipid microbubbles and the stabilization effect of sinapultide on the shells of lipid microbubbles. Journal of Materials Chemistry B, 6 (9), 1335-1341.

3. Lal, M. K., & Sinha, S. K. (2008). Surfactant respiratory therapy using Surfaxin/sinapultide. Therapeutic advances in respiratory disease, 2 (5), 339-344.