Several novel formulations of perfluorocarbon-based emulsions for use as respiratory gas-carrying fluids were developed and evaluated in relevant biological systems, including specially-developed in vitro bioassays. Some of the new emulsions incorporated novel and highly-purified fluoro-surfactants and newly-synthesised fluorinated stabilisers which significantly improved emulsion stability and increased storage time. The emulsions were steam sterilisable and storable at room temperature for over 1 year. In vivo gross toxicity assessments of selected emulsions at clinically-relevant doses showed satisfactory results. Some emulsions were assessed as perfusates of isolated vertebrate organs, where ex-vitro vital functions were markedly improved. Some of the novel fluoro-surfactants inhibited human platelet aggregation in vitro in a dose-dependent manner, suggesting novel and clinically-important potential applications as anti-thrombotic agents.
The proposed research is directed at developing an oxygen-carrying system based on perfluorocarbon emulsified in physiological saline solution. It will provide enhanced medical care in cases of surgery, organ transplantation, diagnostic and emergency. The oxygen-carrying system will be characterized by improved long term storability at ambient and body temperature (emulsions of third generation) and by tailor made composition and quality for special applications. The major research tasks are:
(i) Development of perfluorocarbons of improved emulsifiability and aspiration rates.
(ii) Improvement of perfluorocarbon emulsifiability through cosurfactants (semifluorinated hydrocarbons or heterocyclic perfluorinated hydrocarbons) which reduce interfacial forces.
(iii) Development of appropriate fluorosurfactants which reduce particle size growth.
(iv) Design and development of tailor made perfluorocarbon emulsions for special application areas.
(v) Development of toxicity and biocompatibility criteria by combining cell culture tests and animal experiment (to reduce number of animal experiments).
Successful completion would provide improved transfusion media (enhanced oxygen transport to tissue), diagnostic tools (imaging tornography, sonography), oxygenating media for transplantation surgery (transport and long term storage of organs) and natural blood substitutes in developing countries.
Funding SchemeCSC - Cost-sharing contracts
NG7 2RD Nottingham