Optimization and Testing of Injectable Oxygen Gas Microparticles for Acute Respiratory Failure
Abstract
Oxygen is a nutrient that is continuously supplied to every cell in the body for energy production. Oxygen, which composes 21% of air, passes through the airways and lungs, and is carried by red blood cells to tissues. This supply is continuously replenished, and if it is interrupted for more than a few seconds can result in permanent injury to the brain, heart, and other organs. There are several ways in which the body s oxygen supply can be interrupted. On the battlefield, for example, face or neck trauma can block a Warfighter s airway, and inhalation injuries can create acute lung injury. Medical patients may suffer from acute asthma, anaphylaxis, pneumothorax, emphysema, or lung injury from any of a long list of etiologies. Whether on the battlefield or in a critically ill patient, acute oxygen deprivation is immediately life-threatening. Such patients are treated with concentrated oxygen, opening of the airways (e.g., placement of a breathing tube), and the use of a ventilator. In extreme circumstances, patients may require the use of a heart-lung bypass machine to support oxygenation. Each of these interventions requires expertise and specialized equipment, and most importantly, time to implement. For example, on the battlefield, support of an oxygen-deprived patient may require placement of a breathing tube (overcoming gunfire, poor lighting, patient positioning, or facial trauma, for example), supplemental oxygen administration (requiring a compressed oxygen source), and mechanical ventilation (requiring a device), all taking place during a critical evacuation period. When such interventions are delayed, Warfighters may suffer irreversible brain injury or death. This project describes a method of administering oxygen to patients in life-threatening circumstances using an intravenous catheter. Oxygen gas is packaged into hollow microparticles, which do not contain perfluorocarbons or hemoglobin substitutes. Instead, the gas is packaged directly into the particle, where it diffuses to oxygen-deprived areas following injection. Using early prototypes, we have shown that microparticles infused into the bloodstream can keep animals alive for 15 minutes without breathing, preventing subsequent organ damage. Conversely, all animals treated with standard therapy died within 10 minutes. This drug could be added to standard intravenous fluids to support Warfighters during a critical evacuation period or medical patients during emergency procedures, such as placement of a breathing tube. The work that we propose in this grant will address problems we uncovered with early prototypes and advance the therapy closer to clinical trials. Early prototypes were made of self-assembling phospholipids, essentially micron-sized soap bubbles containing oxygen. Despite effectively encapsulating large volumes of oxygen, these prototypes break apart easily, releasing gas into the bloodstream when injected quickly, making them impossible to filter before injection. Thus, in work funded by a Defense Medical Research and Development Program Basic Research Award, we have developed methods for the bulk manufacture of microparticles made of a biocompatible polymer used in several Food and Drug Administration (FDA)-approved medications. These microparticles effectively contain and release oxygen in vitro with similar efficacy to early prototypes, but add significant diversity to create a platform technology. For example, microparticle shells can be engineered for delayed release following injection, to contain oxygen under pressure (to increase their oxygen carrying capacity), and withstand prolonged storage as a powder. We believe that this project aligns with the Peer Reviewed Medical Research Program 2014 Topic Area: Respiratory Health. Building on prior work, we propose the following. In Aim I, we will optimize the manufacturing process in order to maximize the oxygen carrying capacity of microparticles, including p
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 29, 2016
- Source ID
- W81XWH1510544
Entities
People
- John N Kheir
Organizations
- United States Army