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 polymerbased 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.hypoxemia | microparticle | oxygen | core-shell | colloids

Interfacial Nanoprecipitation toward Stable and Responsive Microbubbles and Their Use as a Resuscitative Fluid

“…100 nm, Figure 2E). [21] MBs can be loaded with different gases through passive purging,t hus indicating the shells are gas-permeable (Figure S8 C). Conceivably,p H-triggered deprotonation of COOH within the shells quickly rendered the shells more hydrophilic,t hereby permitting water influx and gas egress.…”

“…Furthermore,w ec onducted experiments to compare the safety profile of DAS-h MBs to DAS-l MBs,aswell as other previously reported IVO 2 microcarriers,namely,LOMs [4] and PLGA microcapsules [21] (see the Supporting Information). Figure 4shows that DAS-h is the only carrier to safely deliver up to 12 mL of gas,w hile the other carriers all resulted in deaths at lower dosages.T his difference is readily explained from the PVR measurements recorded during safety studies, where DA MBs,P LGA microcapsules,D AS-l MBs,a nd LOMs,w hose shells cannot rapidly self-eliminate,i nvariably caused significant increase in PVR to various degrees ( Figures S17-S20).…”

Injectable Oxygen: Interfacing Materials Chemistry with Resuscitative Science

“…Recently, Seekell et al. created poly(lactic‐co‐glycolic acid) (PLGA)‐based oxygen‐filled polymeric hollow microcapsules (PHMs) and evaluated their potential use as intravascular gas carriers . To overcome the low oxygen permeability of polyesters, such as PLGA, the authors developed a novel method to fabricate nanoporous core–shell PHMs using a novel PFOB‐templated emulsion phase separation technique (Figure A).…”

“…Motivated by the need for an effective solution to treat patients suffering from severe hypoxemia, our laboratory has developed oxygen microbubbles (Ox‐MBs) as an alternative i.v. oxygen carrier . This article will provide a brief review of several biomaterial‐based technologies available for intravascular oxygen delivery in the context of treating severe hypoxemia, with an emphasis on cardiac arrest.…”

“…[8] However, there remains no FDA-approved therapeutic for intravenous oxygen delivery.M otivated by the need for an effective solution to treat patients sufferingfrom severe hypoxemia,our laboratory has developed oxygen microbubbles (Ox-MBs) as an alternative i.v.o xygen carrier. [9][10][11] Thisa rticle will provide ab rief review of severalb iomaterial-basedt echnologiesa vailable for intravascular oxygen delivery in the context of treatings evere hypoxemia,w ith an emphasis on cardiac arrest. We discuss the importance of understanding both the materials properties and disease pathophysiology when designing biomaterialbased gas carriers for improved i.v.o xygen delivery,i nv ivo safety,a nd therapeutic outcomes.…”