title: Oxygen delivery using engineered microparticles.
abstract: 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.
authors: Division of Basic Cardiovascular Research, Department of Cardiology, Boston Children's Hospital, Boston, MA 02115.|Department of Pediatrics, Harvard Medical School, Boston, MA 02115.
authors: Raymond P
authors: RP
authors: Seekell
authors: Division of Basic Cardiovascular Research, Department of Cardiology, Boston Children's Hospital, Boston, MA 02115.
authors: Andrew T
authors: AT
authors: Lock
authors: Division of Basic Cardiovascular Research, Department of Cardiology, Boston Children's Hospital, Boston, MA 02115.|Department of Pediatrics, Harvard Medical School, Boston, MA 02115.
authors: Yifeng
authors: Y
authors: Peng
authors: Division of Basic Cardiovascular Research, Department of Cardiology, Boston Children's Hospital, Boston, MA 02115.
authors: Alexis R
authors: AR
authors: Cole
authors: Division of Basic Cardiovascular Research, Department of Cardiology, Boston Children's Hospital, Boston, MA 02115.|Department of Pediatrics, Harvard Medical School, Boston, MA 02115.
authors: Dorothy A
authors: DA
authors: Perry
authors: Division of Basic Cardiovascular Research, Department of Cardiology, Boston Children's Hospital, Boston, MA 02115.|Department of Pediatrics, Harvard Medical School, Boston, MA 02115.
authors: John N
authors: JN
authors: Kheir
authors: Division of Basic Cardiovascular Research, Department of Cardiology, Boston Children's Hospital, Boston, MA 02115; brian.polizzotti@cardio.chboston.org.|Department of Pediatrics, Harvard Medical School, Boston, MA 02115.
authors: Brian D
authors: BD
authors: Polizzotti
mesh_terms: D000818:Animals; D002214:Capsules / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D006801:Humans; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D058608:Nanopores; D010100:Oxygen / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D016062:Porosity; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
chemical_list: D002214:Capsules; D011108:Polymers; D010100:Oxygen
keywords: colloids; core–shell; hypoxemia; microparticle; oxygen