Digoxin-N preclinical dose escalation

Digoxin- Novochizol (Digoxin -N) was formulated as an aqueous solution containing 2% Novochizol and 1.8 mg/ml Digoxin.

The solution was nebulized (with an ultra-sound nebulizer) and used in preclinical “dose-escalation” experiments on rats to determine accumulation in lung epithelia, acute toxicity and systemic distribution, according to the scheme below:

Fluorescein-labeled Novochizol was also used in a parallel experiment for histological examinations of lung tissues (ongoing).

The brigth red beam in the inhalation chamber is caused by the nanoparticles reflecting the light from a pocket laser beam.

In spite of high dose digoxin inhalation ( ranging between 100 and 200 micrograms per minute over a period of 8 hours), all animals appeared healthy.
Macroscopic examination of lungs did not reveal any gross alterations. Histological examinations and blood analyses are under way.

This rat has likely received the equivalent of multiple lethal doses of digoxin  (6 hours of inhalation of 100 ug/min, followed  by 2 hours of 200 g/min Digoxin as Digoxin-N aerosol)