Intravenous oxygen delivery edges toward the clinic

intravenous-oxygen-delivery
Engineered microparticles that deliver oxygen straight to the bloodstream in emergency situations

Sudden oxygen deprivation can happen for many reasons, from choking to aspiration to cardiac arrest. In these emergency situations, rapid oxygen delivery can mean the difference between life and death. But what if the person cannot breathe?

In the summer of 2012, John Kheir, MD, of the Heart Center at Boston Children’s Hospital, published a study in Science Translational Medicine describing an alternative oxygen delivery system. Kheir used tiny, gas-filled microparticles with a thin outer layer of lipids (fatty molecules) that combined to form a liquid foam-like substance. Injected into the bloodstream, the particles rapidly dissolved and delivered oxygen gas directly to the red blood cells in animal models. But the bubbles were very unstable and not suitable for clinical use.

Recognizing the limitations of the technology, Kheir partnered with bioengineer Brian Polizzotti, PhD, a staff scientist in the Division of Basic Cardiovascular Research. Polizzotti’s extensive experience in materials science, biotechnology and chemical engineering synergized well with Kheir’s expertise in cardiovascular physiology. Together, they established the Translational Research Laboratory (TRL).

“We share money, we share space, and we share one mission,” says Kheir. “To bring intravenous oxygen to the clinic.”

Building a better oxygen microparticle: Lather, rinse, re-work

This fall, the TRL has revealed a new formulation, described in the Proceedings of the National Academy of Sciences (PNAS), that brings oxygen therapy one step closer to the patient bedside.

In the old formulation, the microparticles would break down immediately at the point of injection, and thus weren’t safe for use on patients who weren’t hypoxic. “It’s not that more oxygen is bad,” says Polizotti, “but when gas bubbles break and coalesce into larger bubbles in the bloodstream, they can create lethal obstructions.”

“The first version of our microparticle was like a bubble,” elaborates Kheir. “It could pop at the slightest touch; it could combine with other particles at random; and once oxygen release began, the rate was uncontrollable.”

The new particles don’t release their gas until the body is in a state of true oxygen deprivation. Its design allows for more regulated gas transport, as oxygen can be loaded in and exported out.

“The newer version is built more like an eggshell, or a balloon,” says Polizzotti. “We used polymers instead of lipids and developed a chemistry that introduced pores to that outer layer.”

IV oxygen
The Kheir-Polizzotti Lab. Top row (left to right): Raymond Seekell, John Kheir, Brian Polizzotti, Ravi Thakur, Ali Ataollahi. Bottom row: Jemima Lamothe, Xiaoqui Tang, Alexis Cole, Yifeng Peng

Next steps in IV oxygen delivery

Further enhancements will soon be submitted for publication, say Kheir and Polizzotti. After that, they hope to make the therapy available to patients through clinical trials.

“Our third generation of particles is truly unique,” says Polizzotti. “The therapy’s success in animal model of cardiac arrest is undeniable: rats that hadn’t taken a breath in 10 minutes came back to life with this therapy.”

The new formulation is stable when stored at room temperature for six months and the team has already engineered a system to produce it on a large scale.

The next step for the lab is to expand on the microparticles’ functionality.

“Once oxygen is restored, tissues can get injured,” notes Polizzotti. “We want to see if we can address that issue, too. Can we combine other gases with the oxygen? Are there new ways we can visualize oxygen deprivation?”

TRL scientists and researchers from a variety of disciplines, including physicians, chemical engineers, chemists, mechanical engineers and biologists, will help Kheir and Polizzotti tackle these and other questions.

“Our work is driven by clinical need,” says Polizzotti. “Being at Boston Children’s Hospital allows us to interact with clinicians to identify the most important problems seen on a day-to-day basis, [then] work side by side to develop novel solutions and test their efficacy in small and large animal models, in an iterative fashion.”

Learn more about Cardiology Research at Boston Children’s Hospital.