Sinapultide-Loaded Microbubbles Combined with Ultrasound to Attenuate Lipopolysaccharide-Induced Acute Lung Injury in Mice

Abstract

Purpose Pulmonary surfactants (eg, sinapultide) are widely used for the treatment of lung injury diseases; however, they generally induce poor therapeutic efficacy in clinics. In this study, sinapultide-loaded microbubbles (MBs) were prepared and combined with ultrasound (US) treatment as a new strategy for improved treatment of lung injury diseases. Methods The combination treatment strategy of MBs combined with ultrasound was tested in a lipopolysaccharide (LPS)-induced mouse model of alveolar epithelial cells (AT II) and acute lung injury. Firstly, cytotoxicity, cytokines, and protein levels in LPS-mediated AT II cells were assessed. Secondly, the pathological morphology of lung tissue, the wet/dry (W/D) weight ratio, cytokines, and protein levels in LPS-mediated acute lung injury mice after treatment with the MBs were evaluated. Moreover, histology examination of the heart, liver, spleen, lung and kidney of mice treated with the MBs was performed to initially evaluate the safety of the sinapultide-loaded MBs. Results Sinapultide-loaded MBs in combination with ultrasound treatment significantly reduced the secretion of inflammatory cytokines and increased the expression of surfactant protein A (SP-A) in AT II cells. Furthermore, the pathological morphology of lung tissue, the wet/dry (W/D) weight ratio, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and SP-A expression level of mice treated with MBs and ultrasound were significantly improved compared to those of non-treated mice. In addition, the histology of the examined organs showed that the MBs had a good safety profile. Conclusion Sinapultide-loaded MBs combined with ultrasonic treatment may be a new therapeutic option for lung injury diseases in the clinic.

Evaluation of the prognostic value of lncRNA UCA1 combined with extravascular lung water index and lung ultrasound score in patients with acute lung injury

“…When severe lung injury is not timely and effectively controlled, it may aggravate lung tissue edema, further impair lung function, and eventually develop into acute RDS, with an overall mortality rate as high as 25%–45% 16 . At present, there is still a lack of effective treatment for ALI in clinic, thus causing serious complications and adverse outcomes 17 . However, the existing chest physical examination lacks specificity in ALI progression.…”

“… 16 At present, there is still a lack of effective treatment for ALI in clinic, thus causing serious complications and adverse outcomes. 17 However, the existing chest physical examination lacks specificity in ALI progression. Therefore, how to predict the severity and prognosis of patients in early stage is of great significance to improve the prognosis of patients.…”

Ultrasound and Microbubbles for Targeted Drug Delivery to the Lung Endothelium in ARDS: Cellular Mechanisms and Therapeutic Opportunities

“…The therapeutic benefits of delivering pulmonary surfactant (sinapultide) using USMB has also been investigated; delivery of sinapultide by insonation of sinapultide-loaded microbubbles reduced the severity of injury and levels of the inflammatory cytokines IL-6 and TNF-α in an LPS-induced model of lung injury [149]. Finally, USMB treatment has also been used to explore the therapeutic effects of delivering a VEGF antagonist (soluble fms-like tyrosine kinase-1) encapsulated in the microbubbles to a murine model of LPSinduced lung injury [150].…”

An Acceptable Concentration (0.1 ppm) of Ozone Exposure Exacerbates Lung Injury in a Mouse Model

“…Eightweek-old female BALB/c mice (Japan SLC, Inc., Shizuoka, Japan) were used, and ALI was developed by intranasal administration of lipopolysaccharide (LPS) (from Escherichia coli O111:B4, Sigma-Aldrich, Tokyo, Japan) 48 h before sacrificing the animals. (3)(4)(5) Mice were exposed to ozone five consecutive days prior to being sacrificed. An acceptable concentration of ozone in Japan and the United States (0.1 ppm) was produced either by ultraviolet light or an electrode (second setting, Tamura Teco Co. Ltd., Osaka, Japan), and concentration of ozone, temperature, and humidity inside the exposure chamber were fully monitored throughout ozone exposure.…”