Sinapultide-loaded lipid microbubbles and the stabilization effect of sinapultide on the shells of lipid microbubbles

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.