Responding to ever increasing need for blood substitutes, scientists have developed two types of artificial oxygen carriers (AOC), polymeric hemoglobin and perfluorocarbon based AOC. While they are capable of supplying oxygen to the tissue, their side effects appear to be one of the most serious and difficult to solve problems, and a novel programmatic approach to this issue might be needed to meet the urgent need. The underlying hypothesis of this project is that if an AOC is removed promptly from the circulating blood once it is no longer needed, their side effects will be diminished, and the slow change in oxygen delivery capacity can even stimulate normal erythropoiesis. Nanoshell Company LLC is interested in developing a technology based on a novel shell protected nanosized perfluorocarbon based AOC developed in preliminary work by University of Utah researchers. These materials should navigate well through the small blood vessels and withstand the turbulence of circulation. They seem to have high oxygen and carbon dioxide solubility, quickly exchange them at the tissue and lungs, and may be further coated with short chain polyethylene oxide to resist endocytosis. Because of their high density (2.0 g/ml), they are good candidate for removal by centrifugation. Our calculations suggests that the centrifugal retrieval will require two-steps of continuous flow centrifugation and the goal of this STTR project if for the University of Utah researchers to help devise a scale-up synthesis procedure suitable for the volumes of material that are practically needed by patients, and to identify the parameters needed for their retrieval from blood obtained from a local blood bank. With these results Nanoshell Company, LLC will work with university researchers to design a commercializable, novel tandem continuous flow centrifugal rotor that will enable us to retrieve these AOC from the circulating blood in one-step. The separation system may also be useful to remove other existing perfluorocarbon-based AOCs, and potentially find other market niches in the separation of cells for medical use. Pending a successful conclusion of this STTR Phase I project, Nanoshell Company, and LLC will invest in construction of a high throughput synthesizer for the retrievable AOC, as well as the fabrication of the prototype, tandem continuous flow centrifugal rotor at its Utah research facility. Nanoshell Company, LLC will then negotiate licensing rights for AOC material production, and arrange for biocompatibility and animal testing in Phase II of this project to prove efficacy and the reduction of side effects with the implementation of retrieval, in animal models, and will contract consultants to assist in the design testing procedures needed to obtain eventual FDA approval for the use of this technology.
The goal of this STTR project is to develop a retrievable artificial oxygen carrier (AOC) material and an optimized centrifugal retrieval system that can be safely used to recover the AOC from the circulating blood of patients once the clinical urgency has passed.
|Liu, Fei; Khan, Anwar A; Chishti, Athar H et al. (2011) Atomic force microscopy demonstration of cytoskeleton instability in mouse erythrocytes with dematin-headpiece and ?-adducin deficiency. Scanning 33:426-36|
|Chen, Yen-Chi; Han, Kyu-Bum; Mizukami, Hiroshi et al. (2010) Fade and quench-resistant emission in calcium phosphate nanoreactors. Nanotechnology 21:455701|