Phospholipid-Stabilized Microbubble Foam for Injectable Oxygen Delivery

Swanson, Edward J.; Mohan, Vickram; Kheir, John N.; Borden, Mark A.

doi:10.1021/la1029432

Cited by 83 publications

(80 citation statements)

References 26 publications

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“…[17][18][19] Recently, there have been some reports regarding the use of microbubbles with special shell reagents for extending the duration of oxygen delivery using ultrasound for local drug delivery. [20][21][22][23][24] However, some problems still need to be resolved, such as the biocompatibility of the shell reagents, microbubble stability, and ultrasonographic damage to the body. Considering the clinical applications for oxygen delivery, an intravenous drip infusion is preferable because infusions possess the flexibility to be administered in large quantities at once and for long periods of time.…”

Section: Introductionmentioning

confidence: 99%

Oxygen supersaturated fluid using fine micro/nanobubbles

Matsuki¹,

Ishikawa²,

Ichiba³

et al. 2014

IJN

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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.

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Section: Introductionmentioning

confidence: 99%

Oxygen supersaturated fluid using fine micro/nanobubbles

Matsuki¹,

Ishikawa²,

Ichiba³

et al. 2014

IJN

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“…However, biocompatibility of the shell reagents and ultrasound damage to the body are major problems that remain to be solved, as also is microbubble stability (Juffermans et al 2006). Reports have also focused on special shell reagents for packing oxygen gas into microbubbles to extend the duration of oxygen delivery for injections (Cavalli et al 2009;Swanson et al 2010). In clinical applications of oxygen delivery to hypoxic patients, intravenous drip infusion is preferable because a large amount can be administered at once or over a long time.…”

Section: Introductionmentioning

confidence: 99%

Blood oxygenation using microbubble suspensions

et al. 2012

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Microbubbles have been used in a variety of fields and have unique properties, for example shrinking collapse, long lifetime, efficient gas solubility, a negatively charged surface, and the ability to produce free radicals. In medicine, microbubbles have been used mainly as diagnostic aids to scan various organs of the body, and they have recently been investigated for use in drug and gene delivery. However, there have been no reports of blood oxygenation by use of oxygen microbubble fluids without shell reagents. In this study, we demonstrated that nano or microbubbles can achieve oxygen supersaturation of fluids, and may be sufficiently small and safe for infusion into blood vessels. Although Po(2) increases in fluids resulting from use of microbubbles were inhibited by polar solvents, normal saline solution (NSS) was little affected. Thus, NSS is suitable for production of oxygen-rich fluid. In addition, oxygen microbubble NSS effectively improved hypoxic conditions in blood. Thus, use of oxygen microbubble (nanobubble) fluids is a potentially effective novel method for oxygenation of hypoxic tissues, for infection control, and for anticancer treatment.

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“…Specifically, a lipid concentration of 10 mg/mL DSPC was necessary to achieve particle stability of at least 30 min consistently. Although, this concentration is higher than lipid concentrations used for the microfluidic manufacturing of liposomes reported in literature (0.3–3.5 mg/mL DSPC), this higher lipid concentration is similar to the concentration used in conventional batch manufacturing of ELIP with or without drug loading (Huang et al 2001, 2008; Swanson et al 2010; Thomson et al 2014). It has been demonstrated previously that increasing the acyl chain length increases the stiffness of microbubbles, resulting in higher resonance frequency and in vivo stability (Borden et al 2005).…”

Section: Discussionmentioning

confidence: 64%

Microfluidic manufacture of rt-PA -loaded echogenic liposomes

Kandadai

Mukherjee

Shekhar

et al. 2016

Biomed Microdevices

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Echogenic liposomes (ELIP), loaded with recombinant tissue-type plasminogen activator (rt-PA) and microbubbles that act as cavitation nuclei, are under development for ultrasound-mediated thrombolysis. Conventional manufacturing techniques produce a polydisperse rt-PA-loaded ELIP population with only a small percentage of particles containing microbubbles. Further, a polydisperse population of rt-PA-loaded ELIP has a broadband frequency response with complex bubble dynamics when exposed to pulsed ultrasound. In this work, a microfluidic flow-focusing device was used to generate monodisperse rt-PA-loaded ELIP (µtELIP) loaded with a perfluorocarbon gas. The rt-PA associated with the µtELIP was encapsulated within the lipid shell as well as intercalated within the lipid shell. The µtELIP had a mean diameter of 5 µm, a resonance frequency of 2.2 MHz, and were found to be stable for at least 30 min in 0.5%bovine serum albumin. Additionally, 35 % of µtELIP particles were estimated to contain microbubbles, an order of magnitude higher than that reported previously for batch-produced rt-PA-loaded ELIP. These findings emphasize the advantages offered by microfluidic techniques for improving the encapsulation efficiency of both rt-PA and perflurocarbon microbubbles within echogenic liposomes.

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Phospholipid-Stabilized Microbubble Foam for Injectable Oxygen Delivery

Cited by 83 publications

References 26 publications

Oxygen supersaturated fluid using fine micro/nanobubbles

Oxygen supersaturated fluid using fine micro/nanobubbles

Blood oxygenation using microbubble suspensions

Microfluidic manufacture of rt-PA -loaded echogenic liposomes

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