Intranasal delivery of diminazene aceturate for nagana and surra treatment

SORAIRES SANTACRUZ MC; FUCHS AG.; FUSCO OA.; HOFFER AM.; ZHANG C.; ZHANG F.; ESTEVA MI.; RIAL MS.; FICHERA LE.; CID N.; GLISONI RJ.; LAID D.; BONTEMPI E.

Buenos Aires

Congreso; Drug Discovery for Neglected Diseases International Congress 2018 4th Scientific Meeting of ResNet NPND; 2018

Instituto de la Química y Metabolismo del Fármaco

The standard treatment for nagana and surra is a single intramuscular (i.m.) dose of diminazene aceturate (DA), an aromatic diamidine. Due to discontinuation of veterinary services in many countries, low income farmers inject animals by themselves. We decided to test a safer and easier delivery route: the intranasal. The drug could travel along the olfactory and trigeminal nerves, arrive to the brain, place where the parasites themselves are found shortly after infection, and from there distribute to the whole body. Several barriers must be crossed, and not every drug has the required features to succeed.Groups of mice were infected with the causative agents (Trypanosoma brucei brucei and Trypanosoma evansi) and treated with DA (alone or with another compounds). Survival time, parasitemia, weight and general aspect were recorded. Furthermore, plasma DA was determinate by HPLC. The results indicate that protection was not achieved with DA alone, but some oils conferred DA the possibility to reach the sanguine fluid and kill the parasites. Fish and several plant oils had different levels of efficacy, and the drug concentration and number of doses were optimized. With the HPLC method we found that although blood was extracted at different time points in the range of 2-60 minutes, all the plasma samples displayed a measurable and approximately constant amount of DA (200 ng/ml) and some animals presented a peak at 15 min (400 ng/ml).This work opens the possibility to test this delivery route with medium and large animals, in order to be adopted by cattle owners and improve their nutritional and financial status.