Oxygen supersaturated fluid using fine micro/nanobubbles

Abstract

Microbubbles show peculiar properties, such as shrinking collapse, long lifetime, high gas solubility, negative electric charge, and free radical production. Fluids supersaturated with various gases can be easily generated using microbubbles. Oxygen microbubble fluid can be very useful for oxygen delivery to hypoxic tissues. However, there have been no reports of comparative investigations into adding fluids containing oxygen fine micro/nanobubbles (OFM-NBs) to common infusion solutions in daily medical care. In this study, it was demonstrated that OFMNBs can generate oxygen-supersaturated fluids, and they may be sufficiently small to infuse safely into blood vessels. It was found that normal saline solution is preferable for generating an oxygen-rich infusion fluid, which is best administered as a 30-minute intravenous infusion. It was also concluded that dextran solution is suitable for drug delivery substances packing oxygen gas over a 1-hour intravenous infusion. In addition, normal saline solution containing OFMNBs was effective for improving blood oxygenation. Thus, the use of OFMNB-containing fluids is a potentially effective novel method for improving blood oxygenation in cases involving hypoxia, ischemic diseases, infection control, and anticancer chemoradiation therapies.

Keywords: fine micro/nanobubble; fluid oxygenation; microbubble; nanobubble; oxygenation.

Figure 1

Experimental system. Notes: (A) Oxygen micro/nanobubbles were generated using a dedicated aerator at a peak pressure of 1–1.5 MPa, through which various solutions (150 mL) were circulated for 15 minutes and oxygen gas was supplied at a flow rate of 1.5 L/minute. Finer micro/nanobubbles of oxygen gas were generated after brief sonication. (B) Macrobubbles were generated through an aquarium air stone for 15 minutes, with oxygen gas supplied in a flow volume of 1.5 L/minute. Abbreviation: min, minute.

Figure 2

Number–size distribution of generated oxygen micro/nanobubbles before and after sonication. Notes: (A) Before brief sonication. The generated microbubbles were divided into two groups: fine microbubbles and relatively large microbubbles. (B) After brief sonication, the generated microbubbles were composed of fine microbubbles with nanobubbles alone.

Figure 3

Potency of oxygen partial pressure increase in ultrapure water by oxygen macrobubbles or oxygen fine micro/nanobubbles. Notes: Oxygen fine micro/nanobubbles were generated using a dedicated micro/nanobubble aerator, with an oxygen gas supply of 1.5 L/minute for 15 minutes, and the immediate application of brief sonication. Oxygen macrobubbles were generated in 150 mL of ultrapure water using porous ceramic with an oxygen gas supply of 1.5 L/minute for 15 minutes. The oxygen partial pressure in ultrapure water was measured by blood gas analysis. Data are presented as the mean ± standard error of the mean of five separate experiments, each performed in duplicate. **P<0.01. Abbreviation: PO₂, partial oxygen pressure.

Figure 4

Time course of the oxygen partial pressure increase by oxygen fine micro/nanobubbles in various infusion solutions. Notes: Each solution was maintained in room air at 25°C after oxygen fine micro/nanobubble treatment. Then, the oxygen partial pressure value of each solution was measured at 0, 15, 30, 60, and 120 minutes. (A) Normal saline solution. (B) Dextran solutions at 5%, 50%, and 100% were expressed as net dextran concentrations of 0.15%, 1.5%, and 3.0%, respectively. (C) Albumin solutions at 0.5%, 1%, and 2% were expressed as net albumin concentrations of 0.22%, 0.44%, and 0.88%, respectively. (D) Lipid solutions at 1%, 5%, and 10% were expressed as net lipid concentrations of 0.2%, 1.0%, and 2.0%, respectively. (E) Summary of normal saline solution, 5.0% dextran solution, 0.5% albumin solution, and 1.0% lipid solution. (F) Comparison of the time-lapse oxygen partial pressure change in normal saline solution, 5.0% dextran solution, 0.5% albumin solution, and 1.0% lipid solution at 0, 60, and 120 minutes. (G) Comparison of the time-lapse residual ratios of the average oxygen partial pressure values of normal saline solution, 5.0% dextran solution, 0.5% albumin solution, and 1.0% lipid solution at 60 and 120 minutes. The oxygen partial pressure value of each solution at 0 minutes was considered as 100%. (A–E) Data are presented as the mean ± standard deviation of four separate experiments, each performed in duplicate. (F and G) Data are presented as the mean ± standard error of the mean of five separate experiments, each performed in duplicate. **P<0.01. Abbreviations: min, minutes; NSS, normal saline solution; PO₂, partial oxygen pressure.

Figure 5

Oxygen partial pressure increments in blood by normal saline solution containing oxygen fine micro/nanobubbles. Notes: Venous swine blood was diluted with normal saline solution containing oxygen fine micro/nanobubbles or normal saline solution at a ratio of 10%, 20%, 30%, and 50%, and shaken gently for 2 minutes. The oxygen partial pressure in blood was immediately measured by blood gas analysis. (A) Potency of oxygen partial pressure increments in blood by normal saline solution or normal saline solution containing oxygen fine micro/nanobubbles. (B) Comparison of increase in oxygen partial pressure ratios in blood against the control between normal saline solution and normal saline solution containing oxygen fine micro/nanobubbles. (C) Comparison of oxygen partial pressure increments in blood at a dilution of 10% with normal saline solution or normal saline solution containing oxygen fine micro/nanobubbles. (D) Oxygen partial pressure increments in blood at respective dilution ratios with normal saline solution containing oxygen fine micro/nanobubbles. Data are presented as the mean ± standard error of the mean of five separate experiments, each performed in duplicate. *P<0.05; **P<0.01. Abbreviations: NSS, normal saline solution; OFMNB-NSS, normal saline solution containing oxygen fine micro/nanobubbles; PO₂, partial oxygen pressure.