Prevention of Organophosphorus Lethality with Anhydrolase (OPA-2) Containing Stealth Liposomes

摘要

The investigational effort was focused on improving the antagonism of anticholinestera organophosphorus agents by alteration of the physiological disposition of the antagonists. Various approaches were employed, but the primary emphasis was placed on prolonging its pharmacological activity by enhancing its duration of action. This was accomplished by forming a cyclodexlium adducts of various pyridinium derivatives. An alternative method was to encapsulate the enzymes organophosphorus acid anhydrolase, OPAA, and organophosphorus hydrolase, OPH, into liposomes and lastly to attach the enzymes to nanotechnology derived particles we called nanostructures and we have termed this area as nanobiotechnology. These approaches have been able to protect and treat animals exposed to the organism phosphoric agents by up to 1000 lethal doses (LD-50). This is the highest protection against an organophosphorus agent ever reported. By using new stable nanostructures and recombinant enzymes which are both relatively easy to produce in mass production procedures by molding molecular biology with nanotechnology. Plans were being protected to examine sarim and saman by these nanobiotechnology approaches.