1. KL4-surfactant prevents hyperoxic and LPS-induced lung injury in mice
Melpo Christofidou-Solomidou, Scott Stephens, Paul Kinniry, Robert Segal, Charalambos C Solomides, Deepika Jain, Jeremy Pick, Ralph Niven Pediatr Pulmonol . 2006 Oct;41(10):916-28. doi: 10.1002/ppul.20468.
KL(4)-surfactant contains the novel KL(4) peptide, sinapultide, which mimics properties of the hydrophobic pulmonary surfactant protein SP-B, in a phospholipid formulation and may be lung protective in experimental acute respiratory distress syndrome/acute lung injury. Our objective was to determine the protective role of airway delivery of KL(4)-surfactant in murine models of hyperoxic and lipopolysaccharide (LPS)-induced lung injury and further explore the mechanisms of protection. For the hyperoxic injury model, mice exposed to 80% O(2) for 6 days received an intranasal bolus of vehicle, beractant, or KL(4)-surfactant on days 3, 4, 5, and 6 of the exposure, and lungs were evaluated on day 7. Mice in the LPS-induced lung injury model received an intratracheal bolus of LPS followed by an intranasal bolus of KL(4)-surfactant or control at 1, 3, and 19 hr post-LPS challenge, and lungs were evaluated after 24 hr. To explore the mechanisms of protection, in vitro assays were performed with human and murine endothelial cell monolayers, and polymorphonuclear leukocyte (PMN) transmigration in the presence or absence of KL(4)-surfactant or lipid controls was evaluated. Based on morphology, histopathology, white blood cell count, percentage of PMNs, and protein concentration in bronchoalveolar lavage fluid, our data showed KL(4)-surfactant, unlike vehicle or beractant, blocked neutrophil influx into alveoli and suppressed lung injury. Furthermore, in vitro assays showed KL(4)-surfactant decreased neutrophil transmigration at the endothelial cell level. KL(4)-surfactant decreased inflammation and lung permeability compared with controls in both mouse models of lung injury. Evidence suggests the anti-inflammatory mechanism of the KL(4)-peptide is through inhibition of PMN transmigration through the endothelium.
2. Sinapultide-loaded lipid microbubbles and the stabilization effect of sinapultide on the shells of lipid microbubbles
Zuoheng Zhang, Juan Jin, Fang Yang, Jing Xing, Ning Gu, Zhiguo Qin, Yang Liu, Dong Liu J Mater Chem B . 2018 Mar 7;6(9):1335-1341. doi: 10.1039/c7tb02799k.
Microbubbles (MBs) hold promise in various biomedical applications due to their ultrasound-responsive properties. However, the stability and contrast enhancement duration of gas encapsulated MBs are still challenging. The aim of this study is to fabricate novel sinapultide (a synthetic pulmonary surfactant) stabilized MBs as ultrasound contrast agents. The optimized MBs generated from a mixture of phospholipid components and sinapultide have an average diameter of 1.82 ± 0.15 μm and a zeta potential of -55.2 ± 3.9 mV. Over 95% of the MBs have a mean diameter of less than 8 μm, indicating that the appropriately sized MBs can be applied as ultrasound contrast agents used in clinic. Furthermore, the interaction between sinapultide and lipid molecules and the stabilization mechanism of sinapultide on the shells of MBs were investigated by molecular dynamics simulation. The results demonstrate that the stability of MBs was increased effectively when the appropriate amount of sinapultide was added due to the decrease of surface tension. Accordingly, acoustic accumulation imaging analysis in vitro indicates that stable gas encapsulated sinapultide loaded MBs can provide a high scattering intensity resulting in better echogenicity. And the optimized concentration of sinapultide-loaded MBs can improve the contrast enhancement effect obviously compared with non-sinapultide MBs. Therefore, sinapultide-loaded lipid MBs may be designed as novel ultrasound contrast agents and used for clinical application in the future.
3. Lucinactant: a novel synthetic surfactant for the treatment of respiratory distress syndrome
Steven M Donn Expert Opin Investig Drugs . 2005 Mar;14(3):329-34. doi: 10.1517/13543784.14.3.329.
Lucinactant (Surfaxin, Discovery Laboratories) is a synthetic surfactant, which contains the novel peptide, sinapultide, a surfactant-associated protein B mimic. Randomised clinical trials suggest that this compound is a safe and effective treatment for respiratory distress syndrome in preterm infants. It is also being actively investigated for other indications, including meconium aspiration syndrome, treatment of bronchopulmonary dysplasia in neonates, acute respiratory distress syndrome and asthma. A novel aerosol formulation administered with nasal continuous positive airway pressure is also under development for treatment of respiratory insufficiency in neonates. Its non-animal origin may make it an attractive alternative to present animal-derived surfactants by eliminating the risks of infection and immunogenicity related to the latter.
