Columbia University

Technology Ventures

Microbubbles for blood oxygenation and drug delivery

Technology #2420

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Researchers
Mark Andrew Borden
Managed By
Richard Nguyen
Patent Protection
US Patent 8,481,077

Every cell in the body requires oxygen to maintain correct homeostasis, and hypoxic conditions can quickly lead to irreversible organ damage or death. Current methods to restore blood oxygen levels in severely ill individuals employ a mechanical ventilator that relies on functioning lung tissue and is known to aggravate tissue, in some cases to the point of severe lung injury. This technology describes improved compositions for blood oxygenation as well as improved methods for producing and delivering these compositions to patients or explanted cells, tissues, or organs. Owing to these advances, this technology holds a wide array of potential utilities for emergency and specialty medicine, pharmaceutical development, and basic research.

Microbubbles are a safe, low-cost and versatile method for rapid and targeted delivery

Using a combination of different lipids, emulsifying agents, preparation and delivery methods this technology offers a wide array of applications, most notably in oxygen delivery that can be tuned for rapid infusion, long-term/sustained oxygenation, and situational or targeted delivery. The microbubbles may also be functionalized with anesthetics, bronchodilators, or therapeutics targeting the central nervous system, along with buffering agents such as nitric oxide, isoflorane, antiepileptics, or saline. The lipid envelopes can also contain proteins or synthetic agents to increase, prolong, or target oxygen/drug delivery such as lung protein mimetics. Further, the technology is well characterized, easy to use, portable, stable, and inexpensive to produce, making rapid and wide distribution possible.

Extensive in vitro experiments led to optimized methodology and compositions while confirming the utility of the technology, initially demonstrating the microbubbles may be kept at room temperature for up to 8 hours with embodiments to increase this to weeks or months. In vivo experiments with a rabbit model of hypoxemic ventilation showed that after a pulse was lost, jugular injection of oxygenated microbubble resulted in a rapid increase of heart rate from 10 to 100 beats per minute and was maintained for up to 90 minutes.

Lead Inventor:

Mark A. Borden, Ph.D.

Applications:

  • Raising the mixed venous, systemic and/or cerebral oxygen content in stroke or heart attack patients, cyanotic congenital heart disease, traumatic brain injury, carbon monoxide poisoning, pulmonary hypertension or acute respiratory distress syndrome (ARDS)
  • An emergency injection device that increases blood oxygen levels in traumatic injuries such as pulmonary arrest or hemorrhagic shock, particularly for use in emergency rooms, first aid and defibrillator kits, ambulances, and combat situations, stabilizing a patient until transfer to definitive care
  • Maintain oxygenation in amputated or near-amputated limbs
  • Oxygen delivery in fetuses, neonates, infants and mothers to treat or prevent premature birth or certain developmental disorders such as cerebral palsy
  • Rapid systemic or targeted delivery of compounds such as nitric oxide, isoflorane, or antiepileptics to treat pain, asthma, or epilepsy, respectively
  • Delivery of oxygenated liquids to cell, tissue and organ culture, ex vivo, for transplantation purposes
  • Basic research protocols including cell, tissue or organ culture
  • Potential for development into chip-based systems requiring gas/drug delivery
  • Potential to be developed into new culture media eliminating the need for bulky and expensive gas incubators

Advantages:

  • Inexpensive and widely available components
  • Customizable
  • Easy to follow protocols
  • Option for a portable kit in emergency or remote situations
  • Option to retain contents until encountering region of hypoxia, stably deliver contents over longer periods of time, or rapidly infuse an area
  • Targeted delivery can often increase effectiveness while reducing side effects compared to systemic infusions
  • Lipid retention after delivery show positive oncotic properties, increasing the blood volume and offering reduced morbidity in events of hemorrhage
  • Oxygen can be retained within the microbubble until it encounters a hypoxic environment, facilitating targeted oxygen delivery to ischemic tissue and organs.
  • Tight control of the size and composition allows for microbubbles to carry gases or other agents to specific areas

Patent Information:

Patent Pending (WO/2009/043031)

Tech Ventures Reference: IR 2420

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