New Paradigm In Fluid Resuscitation Vivacelle Bio, Inc.
VIVACELLE BIO, Inc.is a clinical stage biotechnology company focused on creating products that utilize our patented phospholipid nanoparticle technology. Phospholipid nanoparticles are particles comprised of naturally-occurring phospholipids that form a single layered wall around an oil droplet called a micelle or a doubled layered wall encircling components dissolved in water called a liposome. Combinations of micelles and liposomes of various sizes make up the different phospholipid nanoparticle formulations that we have invented. The Company has two products that have been cleared by the FDA for phase IIa clinical trials. In both cases the FDA permitted Vivacelle Bio to proceed directly to phase IIa skipping phase I based on the well-established safety of all of the components of each product. One product, VBI-S, is designed for the treatment of the hypovolemia and hypotension of septic shock. The clinical trial of VBI-S in patients in whom other fluids have failed to elevate their blood pressure is now in progress at multiple hospitals. The other product VBI-1 is designed for the treatment of severe blood loss. The clinical trial of VBI-1 in patients who lose a large volume of blood during surgery is in the site selection phase. Vivacelle Bio has a pipeline of seven additional products that apply the phospholipid nanoparticle technology to multiple areas of medicine such as traumatic brain injury, organ transplantation, multiple organ dysfunction syndrome and reperfusion injury.
A Novel Approach to Absolute and Relative Hypovolemia.
Hypovolemia is a state in which there is insufficient fluid volume within the blood vessels. This state can lead to inadequate tissue perfusion and death. There are two types of hypovolemia. Absolute hypovolemia occurs when there is loss of fluid from the blood vessels due to factors such as bleeding or leaking of water-based solutions from the blood vessels to the interstitial tissue. Relative hypovolemia occurs when the blood vessels dilate and the volume of fluid is insufficient due to the wide diameter of the blood vessels. In this case the result is the same, tissue perfusion is inadequate. Currently, the approach to absolute hypovolemia has been to replace the lost volume by infusing fluids such as Ringer’s lactate, albumin or blood into the blood vessels. This approach has been successful in replacing the volume. But the infusion of these fluids causes reperfusion injury that damages tissues and increases the chance of developing organ failure. At this time, however, there is no safe way to treat relative hypovolemia. Relative hypovolemia is caused by an overproduction of nitric oxide that occurs in response to inflammation. Vasopressors are used to reverse the dilatation of blood vessels. However, vasopressors can cause the constriction of blood vessels and loss of tissue perfusion resulting in organ failure and worsening acidosis. In addition, nitric oxide overproduction can depress the strength of cardiac contraction and reduce blood flow from the heart. Nitric oxide can also react with other gases that form in severe hypovolemia to form dangerous free radicals that destroy tissue. Attempts to block nitric oxide or to remove it with various chemicals have failed primarily because nitric oxide is needed for the normal functioning of numerous essential biochemical reactions and cellular functions. The question is how can the bioavailability of nitric oxide be diminished while at the same time allowing its production to continue and its normal essential interactions to proceed. Our phospholipid nanoparticle technology solves this problem while at the same time reducing reperfusion injury. The Solution Based upon our preclinical experiments we have found that the phospholipid nanoparticles absorb nitric oxide. The phospholipid nanoparticles can also readily release nitric oxide. This finding suggests that phospholipid nanoparticles could reduce the bioavailability of nitric oxide where it is present in excess and release nitric oxide into areas in which its concentration in insufficient. In effect the nitric oxide is not blocked or scavenged, Instead, it would be redistributed so that the balance is shifted from a greater probability of death to a greater probability of survival. Below are the salutary properties of the phospholipid nanoparticles that we have determined through our preclinical experiments and review.
- Modulates Nitric Oxide (NO), (a potent vasodilator that drops the blood pressure and a precursor to highly toxic mediators)
- Carries oxygen
- Increases blood pressure after severe blood loss
- Reduces reperfusion injury
- Inhibits the inflammatory response
- Metabolizable and naturally-occurring components
- Provides an energy source
These properties open a new door to the discovery of more effective treatment of shock due to infection or bood loss and to a broad range of disease that could save many lives.