Development of a Phospholipid Nanoparticle-based Volume Expander for Blood Volume Replacement and Organ Protection in Hemorrhagic Shock - PROJECT SUMMARY Hemorrhagic shock is a life-threatening condition caused by severe blood loss leading to inadequate oxygenation of cellular tissues. If left untreated, it quickly leads to cardiac arrest, and is a leading cause of preventable death, accounting for up to 40% of civilian trauma and 90% of potentially preventable battlefield fatalities. Type-matched blood is the gold standard for resuscitation in hemorrhagic shock; however, it is often unavailable during emergencies, particularly in low-resource and prehospital settings, due to type-matching requirements, low shelf life, and storage limitations. Even when available, blood transfusion carries risks such as ischemia–reperfusion injury (IRI), infection, respiratory distress, and multi-organ dysfunction, which can lead to long-term damage in survivors. Unfortunately, efforts to develop artificial substitutes for blood have failed due to serious side effects like oxidative stress and even increased mortality. In the absence of blood and its substitutes, FDA-approved volume expanders such as crystalloids (e.g., Ringer’s lactate) and colloids (e.g., albumin) are used to temporarily support circulation. However, crystalloids provide short-lived volume expansion and may cause tissue edema, while colloids do not provide volume expansion for much longer than crystalloids, and can also impair blood clotting and kidney function. Thus, there is an urgent, unmet need for a resuscitation fluid that is safe, effective in resource-limited settings, and restores blood pressure while preserving clotting and protecting against IRI. Vivacelle Bio Inc. (VBI) is addressing this by developing VBI- 160, a phospholipid nanoparticle (PN)-based colloidal volume expander that restores and sustains mean arterial pressure (MAP), reduces IRI, and preserves clotting. Upon infusion, VBI-160’s colloids restore and maintain intravascular volume while also sequestering excess nitric oxide (NO), a key driver of subsequent hemorrhagic shock pathology. In preliminary studies with rat models, resuscitation with VBI-160 matched shed blood in total blood loss, bleed time and MAP elevation, while offering superior organ protection. Therefore, in this Phase I SBIR project, we aim to establish the stability profile, preclinical efficacy, and immunological and cognitive outcomes of VBI-160. In Aim 1, we will characterize VBI-160 for physicochemical properties, sterility, NO uptake/release, and shelf life. In Aim 2, we will assess hemodynamic restoration efficacy of VBI-160 in a fixed-pressure hemorrhagic shock model, compared to shed blood and Ringer’s lactate, through serial blood analysis and terminal tissue assessment. Finally, we will evaluate the immunomodulatory and cognitive effects of VBI-160 through flow cytometry, ELISA, and behavioral tests (Aim 3). Successful completion of these aims will position VBI-160 for CMC manufacturing and subsequent clinical validation as a safe and effective resuscitation fluid for hemorrhagic shock that reduces dependence on donor blood in both civilian and battlefield care.
