Administration of Drugs/Gene Products to the Respiratory System: A Historical Perspective of the Use of Inert Liquids

Abstract

The present review is a historical perspective of methodology and applications using inert liquids for respiratory support and as a vehicle to deliver biological agents to the respiratory system. As such, the background of using oxygenated inert liquids (considered a drug when used in the lungs) opposed to an oxygen-nitrogen gas mixture for respiratory support is presented. The properties of these inert liquids and the mechanisms of gas exchange and lung function alterations using this technology are described. In addition, published preclinical and clinical trial results are discussed with respect to treatment modalities for respiratory diseases. Finally, this forward-looking review provides a comprehensive overview of potential methods for administration of drugs/gene products to the respiratory system and potential biomedical applications.

Perfluorocarbons in Research and Clinical Practice: A Narrative Review

“…This "liquid PEEP" might also collapse pulmonary vessels in the dependent lung, diverting blood flow to the gas-filled nondependent lung regions, thereby improving V/Q matching. 5 Both TLV and PLV can achieve lower ventilatory pressures and smaller tidal volumes compared with conventional gas ventilation. 11,12,16,17,26 As the PFCs evaporate out of the lungs, they are gradually replaced to maintain the total liquid volume of FRC.…”

“…This “liquid PEEP” might also collapse pulmonary vessels in the dependent lung, diverting blood flow to the gas-filled nondependent lung regions, thereby improving V/Q matching. 5…”

“…Several studies have shown the ability of PFCs to increase drug delivery while reducing the side effects related to their systemic administration. 5,70–74…”

“…Several studies have shown the ability of PFCs to increase drug delivery while reducing the side effects related to their systemic administration. 5,[70][71][72][73][74] Animal models demonstrated that gentamicin and vancomycin administration during PLV with PFCs resulted in higher lung concentration compared with intravenous administration and less systemic side effects. 70,71 Similarly, surfactant delivery with PLV allowed a more uniform distribution in both lungs compared with CMV and was associated with improved lung compliance and systemic oxygenation.…”

“…Vehicles for delivery of antibiotic, gene, or cancer therapies directly to the lung. 5 2. Nonadhesive coatings for extracorporeal membrane oxygenation circuits to prevent plasma protein and thrombus deposition.…”