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      Drug Design, Development and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the design and development of drugs, as well as the clinical outcomes, patient safety, and programs targeted at the effective and safe use of medicines. Sign up for email alerts here.

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

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          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.

          Most cited references35

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          Acute lung injury and the acute respiratory distress syndrome: a clinical review.

          Arthur Wheeler, Gordon Bernard (2007)
          Acute respiratory distress syndrome and acute lung injury are well defined and readily recognised clinical disorders caused by many clinical insults to the lung or because of predispositions to lung injury. That this process is common in intensive care is well established. The mainstay of treatment for this disorder is provision of excellent supportive care since these patients are critically ill and frequently have coexisting conditions including sepsis and multiple organ failure. Refinements in ventilator and fluid management supported by data from prospective randomised trials have increased the methods available to effectively manage this disorder.
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            Surfactant proteins SP-A and SP-D: structure, function and receptors.

            Taruna Madan, Rohit Ghai, Patrick Waters … (2006)
            Surfactant proteins, SP-A and SP-D, are collagen-containing C-type (calcium dependent) lectins called collectins, which contribute significantly to surfactant homeostasis and pulmonary immunity. These highly versatile innate immune molecules are involved in a range of immune functions including viral neutralization, clearance of bacteria, fungi and apoptotic and necrotic cells, down regulation of allergic reaction and resolution of inflammation. Their basic structures include a triple-helical collagen region and a C-terminal homotrimeric lectin or carbohydrate recognition domain (CRD). The trimeric CRDs can recognize carbohydrate or charge patterns on microbes, allergens and dying cells, while the collagen region can interact with receptor molecules present on a variety of immune cells in order to initiate clearance mechanisms. Studies involving gene knock-out mice, murine models of lung hypersensitivity and infection, and functional characterization of cell surface receptors have revealed the diverse roles of SP-A and SP-D in the control of lung inflammation. A recently proposed model based on studies with the calreticulin-CD91 complex as a receptor for SP-A and SP-D has suggested an anti-inflammatory role for SP-A and SP-D in naïve lungs which would help minimise the potential damage that continual low level exposure to pathogens, allergens and apoptosis can cause. However, when the lungs are overwhelmed with exogenous insults, SP-A and SP-D can assume pro-inflammatory roles in order to complement pulmonary innate and adaptive immunity. This review is an update on the structural and functional aspects of SP-A and SP-D, with emphasis on their roles in controlling pulmonary infection, allergy and inflammation. We also try to put in perspective the controversial subject of the candidate receptor molecules for SP-A and SP-D.
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              Combining Nanomedicine and Immunotherapy

              Yang Shi, Twan Lammers (2019)
              Nanomedicine holds significant potential to improve the efficacy of cancer immunotherapy. Thus far, nanomedicines – i.e. 1-100(0) nm-sized drug delivery systems – have been primarily used to improve the balance between the efficacy and the toxicity of conjugated or entrapped chemotherapeutic drugs. The clinical performance of cancer nanomedicines has been somewhat disappointing, which is arguably mostly due to the lack of tools and technologies for patient stratification. Conversely, the clinical progress made with immunotherapy has been spectacular, achieving complete cures and inducing long-term survival in advanced-stage patients. Unfortunately, however, immunotherapy only works well in relatively small subsets of patients. Increasing amounts of pre-clinical and clinical data demonstrate that combining nanomedicine with immunotherapy can boost therapeutic outcomes, by turning “cold” non-immunoresponsive tumors and metastases into “hot” immunoresponsive lesions. Nano-immunotherapy can be realized via three different approaches, in which nanomedicines are used (1) to target cancer cells, (2) to target the tumor immune microenvironment, and (3) to target the peripheral immune system. When targeting cancer cells, nanomedicines typically aim to induce immunogenic cell death, thereby triggering the release of tumor antigens and danger-associated molecular patterns, such as calreticulin, high mobility group box 1 protein and adenosine triphosphate. The latter serve as adjuvants to alert antigen-presenting cells to take up, process and present the former, thereby promoting the generation of CD8 + cytotoxic T cells. Nanomedicines targeting the tumor immune microenvironment potentiate cancer immunotherapy by inhibiting immunosuppressive cells, such as M1-like tumor-associated macrophages, as well as by reducing the expression of immunosuppressive molecules, such as transforming growth factor beta. In addition, nanomedicines can be employed to promote the activity of antigen-presenting cell and cytotoxic T cells in the tumor immune microenvironment. Nanomedicines targeting the peripheral immune system aim to enhance antigen presentation and cytotoxic T cell production in secondary lymphoid organs, such as lymph nodes and spleen, as well as to engineer and strengthen peripheral effector immune cell populations, thereby promoting anticancer immunity. While the majority of immunomodulatory nanomedicines are in pre-clinical development, exciting results have already been reported in initial clinical trials. To ensure efficient translation of nano-immunotherapy constructs and concepts, we have to consider biomarkers in clinical development, to make sure that the right nanomedicine formulation is combined with the right immunotherapy in the right patient. In this context, we have to learn from currently ongoing efforts in nano-biomarker identification, as well as from partially already established immuno-biomarker-initiatives, such as the Immunoscore and the cancer immunogram. Together, these protocols will help to capture the nano-immuno-status in individual patients, enabling the identification and use of individualized and improved nanomedicine-based treatments to boost the performance of cancer immunotherapy.
              Article 0 comments Cited 142 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Drug Des Devel Ther
                Journal ID (iso-abbrev): Drug Des Devel Ther
                Journal ID (publisher-id): dddt
                Journal ID (pmc): dddt
                Title: Drug Design, Development and Therapy
                Publisher: Dove
                ISSN (Electronic): 1177-8881
                Publication date (Electronic): 22 December 2020
                Publication date Collection: 2020
                Volume: 14
                Pages: 5611-5622
                Affiliations
                [1 ]School of Biological and Pharmaceutical Engineering, West Anhui University , Lu’an 237012, People’s Republic of China
                [2 ]Anhui Engineering Laboratory for Conservation and Sustainable Utilization of Traditional Chinese Medicine Resources , Lu’an 237012, People’s Republic of China
                [3 ]School of Biomedical Sciences and Medical Engineering, Southeast University , Nanjing 210009, People’s Republic of China
                [4 ]Department of Analytical Chemistry, China Pharmaceutical University , Nanjing 210009, People’s Republic of China
                [5 ]Key Laboratory of Biomedical Functional Materials, China Pharmaceutical University , Nanjing 210009, People’s Republic of China
                Author notes
                Correspondence: Deli XiaoDepartment of Analytical Chemistry, China Pharmaceutical University , Nanjing210009, People’s Republic of ChinaTel +86 25 86185160 Email xiao49562001@163.com
                Bangxin HanSchool of Biological and Pharmaceutical Engineering, West Anhui University , Lu’an237012, People’s Republic of ChinaTel +86 564 3305073 Email hanbx1978@sina.com
                Article
                Publisher ID: 282227
                DOI: 10.2147/DDDT.S282227
                PMC ID: 7764709
                SO-VID: 4709cb98-c4a3-4f47-bd0b-6faae97a0cbf
                Copyright © © 2020 Liu et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 17 September 2020
                Date accepted : 19 November 2020
                Page count
                Figures: 7, Tables: 2, References: 35, Pages: 12
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: sinapultide,microbubbles,lipopolysaccharide,lung injury,safety
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: sinapultide, microbubbles, lipopolysaccharide, lung injury, safety

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