Drug Design, Development and Therapy (Dec 2020)
Sinapultide-Loaded Microbubbles Combined with Ultrasound to Attenuate Lipopolysaccharide-Induced Acute Lung Injury in Mice
Abstract
Dong Liu,1– 3 Yanjun Chen,1,2 Fang Li,1,2 Cunwu Chen,1,2 Peipei Wei,1,2 Deli Xiao,4,5 Bangxin Han1,2 1School of Biological and Pharmaceutical Engineering, West Anhui University, Lu’an 237012, People’s Republic of China; 2Anhui Engineering Laboratory for Conservation and Sustainable Utilization of Traditional Chinese Medicine Resources, Lu’an 237012, People’s Republic of China; 3School of Biomedical Sciences and Medical Engineering, Southeast University, Nanjing 210009, People’s Republic of China; 4Department of Analytical Chemistry, China Pharmaceutical University, Nanjing 210009, People’s Republic of China; 5Key Laboratory of Biomedical Functional Materials, China Pharmaceutical University, Nanjing 210009, People’s Republic of ChinaCorrespondence: Deli XiaoDepartment of Analytical Chemistry, China Pharmaceutical University, Nanjing 210009, People’s Republic of ChinaTel +86 25 86185160Email [email protected] HanSchool of Biological and Pharmaceutical Engineering, West Anhui University, Lu’an 237012, People’s Republic of ChinaTel +86 564 3305073Email [email protected]: 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.Keywords: sinapultide, microbubbles, lipopolysaccharide, lung injury, safety
