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Oxygen delivery using engineered microparticles

Significance The clinical treatment of profound oxygen deprivation (hypoxemia) is time sensitive and requires skill and specialized equipment. When the airways or lungs become incapacitated (e.g., due to airway obstruction or lung injury), resuscitation is ineffective until oxygenation is restored. Many critically ill patients suffer organ dysfunction, cardiac arrest, or death within minutes. In this work, we describe a polymeric microparticle-based oxygen delivery technology capable of rapidly administering large volumes of oxygen gas through an intravenous line. A continuous supply of oxygen to tissues is vital to life and interruptions in its delivery are poorly tolerated. The treatment of low-blood oxygen tensions requires restoration of functional airways and lungs. Unfortunately, severe oxygen deprivation carries a high mortality rate and can make otherwise-survivable illnesses unsurvivable. Thus, an effective and rapid treatment for hypoxemia would be revolutionary. The i.v. injection of oxygen bubbles has recently emerged as a potential strategy to rapidly raise arterial oxygen tensions. In this report, we describe the fabrication of a polymer-based intravascular oxygen delivery agent. Polymer hollow microparticles (PHMs) are thin-walled, hollow polymer microcapsules with tunable nanoporous shells. We show that PHMs are easily charged with oxygen gas and that they release their oxygen payload only when exposed to desaturated blood. We demonstrate that oxygen release from PHMs is diffusion-controlled, that they deliver approximately five times more oxygen gas than human red blood cells (per gram), and that they are safe and effective when injected in vivo. Finally, we show that PHMs can be stored at room temperature under dry ambient conditions for at least 2 mo without any effect on particle size distribution or gas carrying capacity.