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 to design products that increase the survivability of critically-ill patients. Our phospholipid nanoparticles are very small (7-300mm) 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 critical 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. Our research has revealed that particles of different sizes possess different properties that are beneficial in specific conditions of critical illness. Vivacelle Bio, Inc. 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 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. This trial is supported by a 5.3 million dollar grant from the Naval Medical Research Center. The other product VBI-1 is designed for the treatment of severe blood loss. Vivacelle Bio has a pipeline of additional products at various stages of development applicable to multiple areas of medicine such as but not limited to 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 and relative. Absolute hypovolemia occurs when there is fluid loss from the blood vessels due to bleeding or leaking of water-based solutions from the blood vessels into the interstitial tissue. Relative hypovolemia occurs when the blood vessels dilate and as a result the fluid volume in the blood vessels becomes relatively low. In either situation, the result is the same, tissue perfusion becomes inadequate. Currently, the approach for 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 successfully replaces the volume, but the infusion of these fluids causes reperfusion injury that damages the tissues and increases the chance of developing organ failure. Currently, there is no safe way to treat relative hypovolemia. Relative hypovolemia is caused by the excessive nitric oxide production in response to inflammation. Vasopressors are used to control the dilatation of blood vessels. However, vasopressors constrict the blood vessels leading to loss of tissue perfusion resulting in organ failure and worsening acidosis. Vasopressors also increase the chance of failure of the kidneys and liver and gangrene of fingers and toes. In addition, the overproduction of nitric oxide can depress the strength of cardiac contraction and reduce blood flow from the heart. Nitric oxide can also combine with other gases that come from severe hypovolemia to form dangerous free radicals that lead to tissue destruction. Efforts to block, or to remove nitric oxide with various chemicals have failed primarily because nitric oxide is essential for the normal functioning of biochemical reactions and cellular functions in the body. The challenge is to reduce the bioavailability of nitric oxide while allowing the continuation of nitric oxide production for normal essential interactions. Our phospholipid nanoparticles solve this problem while reducing reperfusion injury. Based upon our preclinical experiments we have found that the phospholipid nanoparticles absorb nitric oxide and also readily release it. The determinant of absorption or release is the concentration gradient. In effect the phospholipid nanoparticles redistribute nitric oxide so that the balance is shifted from a greater probability of death to a greater probability of survival. The salutary properties of the phospholipid nanoparticle fluids were determined based on our preclinical experiments and review. These properties are as follows to varying degrees depending on specific particle characteristics such as particle diameter, or aqueous phase constituents.
· 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 and after hypovolemia due to
sepsis/septic shock
· Reduces reperfusion injury
· Acts as a source of energy
These properties open a brand-new door to the discovery of more effective treatment of shock from infection or blood loss and to a broad range of diseases saving many lives.