The
herbicide paraquat has been widely used throughout the world for almost 50 years and is important in sustainable agriculture. When used correctly the chemical poses no known risk to human health. However, it is acutely toxic, and can be fatal, if the concentrated product is ingested orally. Despite many years of research there is no successful treatment for
paraquat intoxication. In recent years we have turned our attention to understanding how we can make the product safer, if it is accidentally or intentionally consumed. We present in this paper a novel approach aimed at safening the
paraquat product,
Gramoxone. Following our previous research on the site and mechanism of
paraquat absorption from the gastrointestinal tract we have identified a new formulation of
paraquat,
Gramoxone INTEON that reduces the absorption of
paraquat into the blood. This new formulation contains the
polysaccharide,
alginate, a
natural product extracted from sea-weed. We have designed a preparation of
paraquat and
alginate with
surfactants that is herbicidally active but has the unique property that it
gels on contact with gastric acid in the stomach. The resulting mixture slows the dispersion and delivery of the toxic chemical to its site of absorption in the small intestine.
Alginates also protect the mucosa against the damaging influence of topical gastric irritants, like
paraquat. Our studies have shown that increasing the loading of
alginate between 7 and 17 g/L causes a dose-related reduction in
paraquat absorption in vitro in isolated rat ileum. This is also observed in vivo, as measured by
paraquat plasma kinetics in the rabbit where the Area Under Curve (AUC 0-24h) was reduced from 33.8+/-3 for
Gramoxone to 12.5+/-6 (microg/mL)h for a formulation containing 17 g/L
alginate. Such a reduction in systemic exposure to
paraquat is expected to reduce the acute oral toxicity of the formulation. This should be particularly effective in a
vomiting species such as man since we have shown in this investigation that
alginates not only reduce the peak plasma
paraquat values but also delay the time to peak levels. This provides the opportunity for a more effective
emetic response since the highly viscous gelled material should remain in the stomach for longer than the liquid
Gramoxone. Further research is required to understand and optimise the safening and herbicidal characteristics of these
alginate acid-triggered gel formulations of
paraquat. However, we anticipate that this
alginate technology in
Gramoxone INTEON could have significant benefit in reducing human mortalities associated with the
herbicide.