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

Biomedicines - Tập 9 Số 7 - Trang 803
Rajiv Sanwal1,2, Kushal Joshi3,4,2, Mihails Ditmans5,2, Scott Tsai3,4,2, Warren L. Lee5,1,3,4,6,2
1Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada
2Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Unity Health Toronto, Toronto, ON M5B 1T8, Canada
3Department of Mechanical and Industrial Engineering, Ryerson University, Toronto, ON M5B 2K3, Canada
4Institute of Biomedical Engineering, Science and Technology (iBEST), Toronto, ON M5B 1T8, Canada
5Biomedical Engineering Graduate Program, Ryerson University, Toronto, ON M5B 2K3, Canada
6Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto ON M5S 1A1, Canada

Tóm tắt

Acute respiratory distress syndrome (ARDS) is characterized by increased permeability of the alveolar–capillary membrane, a thin barrier composed of adjacent monolayers of alveolar epithelial and lung microvascular endothelial cells. This results in pulmonary edema and severe hypoxemia and is a common cause of death after both viral (e.g., SARS-CoV-2) and bacterial pneumonia. The involvement of the lung in ARDS is notoriously heterogeneous, with consolidated and edematous lung abutting aerated, less injured regions. This makes treatment difficult, as most therapeutic approaches preferentially affect the normal lung regions or are distributed indiscriminately to other organs. In this review, we describe the use of thoracic ultrasound and microbubbles (USMB) to deliver therapeutic cargo (drugs, genes) preferentially to severely injured areas of the lung and in particular to the lung endothelium. While USMB has been explored in other organs, it has been under-appreciated in the treatment of lung injury since ultrasound energy is scattered by air. However, this limitation can be harnessed to direct therapy specifically to severely injured lungs. We explore the cellular mechanisms governing USMB and describe various permutations of cargo administration. Lastly, we discuss both the challenges and potential opportunities presented by USMB in the lung as a tool for both therapy and research.

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