Injectable oxygenation therapeutics: evaluating the oxygen delivery efficacy of artificial oxygen carriers and kosmotropes in vitro.

The aim of this paper was to utilise an existing in vitro setup to quantify the oxygen offloading capabilities of two different subsets of injectable oxygenation therapeutics: (1) artificial oxygen carriers (AOCs), which bind or dissolve oxygen and act as transport vectors, and (2) kosmotropes, which increase water hydrogen bonding and thereby decrease the resistance to oxygen movement caused by the blood plasma. Dodecafluoropentane emulsion (DDFPe) was chosen to represent the AOC subset while trans sodium crocetinate (TSC) was selected to represent the kosmotrope subset. PEG-Telomer-B (PTB), the surfactant utilised to encapsulate DDFP in emulsion form, was also tested to determine whether it affected the oxygen transport ability of DDFPe. The in vitro set-up was used to simulate a semi closed-loop circulatory system, in which oxygen could be delivered from the lungs to hypoxic tissues. Results of this study showed that (1) 0.5 ml of a PFC outperformed 6.25 ml of a kosmotrope in a controlled, in vitro setting and (2) that PTB and sucrose do not contribute to the overall oxygen transportation efficacy of DDFPe. These results could be therapeutically beneficial to ongoing and future pre-clinical and clinical studies involving various oxygenation agents.

In vitro model to compare the oxygen offloading behaviour of dodecafluoropentane emulsion (DDFPe).

The aim of this paper was to create an in vitro setup to quantify the oxygen offloading capabilities of dodecafluoropentane emulsion (DDFPe) in a hypoxic environment. Oxygen offloading from DDFPe was characterized under different gaseous environments and under pre-oxygenated conditions. Results of this study showed that (1) oxygen offloading is inversely related to the solubility of the selected sparging gas in saline and (2) both pre-oxygenated and simultaneously oxygenated DDFPe display similar magnitudes of oxygen transport. These results could be applicable to on-going and future studies involving a variety of hypoxic conditions where oxygen delivery might be therapeutically beneficial.

Dodecafluoropentane Emulsion (DDFPE) as a Resuscitation Fluid for Treatment of Hemorrhagic Shock and Traumatic Brain Injury: A Review.

Dodecafluoropentane emulsion (DDFPe) is a novel nanotechnology for oxygen delivery with therapeutic potential for hemorrhagic shock and/or traumatic brain injury (TBI). DDFPe demonstrates efficacy at smaller doses than previously tested perfluorocarbon oxygen therapeutics. This smaller dose potentially eliminates toxicities exhibited by previous oxygen therapeutics, whereas anti-inflammatory properties of DDFPe may alleviate damage from ischemia reperfusion injury. This minireview summarizes our progress in developing a battlefield-ready product to prevent combat death due to hemorrhagic shock and/or TBI. Preclinical studies, for both indications, show promising effects of DDFPe as a resuscitation fluid. DDFPe may become a part of the toolkit for tactical healthcare professionals in battlefield and domestic emergency medicine.

Overcoming tumor hypoxia as a barrier to radiotherapy, chemotherapy and immunotherapy in cancer treatment.

Hypoxia exists to some degree in most solid tumors due to inadequate oxygen delivery of the abnormal vasculature which cannot meet the demands of the rapidly proliferating cancer cells. The levels of oxygenation within the same tumor are highly variable from one area to another and can change over time. Tumor hypoxia is an important impediment to effective cancer therapy. In radiotherapy, the primary mechanism is the creation of reactive oxygen species; hypoxic tumors are therefore radiation resistant. A number of chemotherapeutic drugs have been shown to be less effective when exposed to a hypoxic environment which can lead to further disease progression. Hypoxia is also a potent barrier to effective immunotherapy in cancer treatment. Because of the recognition of hypoxia as an important barrier to cancer treatment, a variety of approaches have been undertaken to overcome or reverse tumor hypoxia. Such approaches have included breathing hyperbaric oxygen, artificial hemoglobins, allosteric hemoglobin modifiers, hypoxia activated prodrugs and fluorocarbons (FCs). These approaches have largely failed due to limited efficacy and/or adverse side effects. Oxygen therapeutics, based on liquid FCs, can potentially increase the oxygen-carrying capacity of the blood to reverse tumor hypoxia. Currently, at least two drugs are in clinical trials to reverse tumor hypoxia; one of these is designed to improve permeability of oxygen into the tumor tissue and the other is based upon a low boiling point FC that transports higher amounts of oxygen per gram than previously tested FCs.