Direct nose to brain delivery of small molecules: critical analysis of data from a standardized <i>in vivo</i> screening model in rats
Deborah Dhuyvetter, Fetene Tekle, М. М. Назаров, Rob J. Vreeken, Herman Borghys, Frederik Rombouts, Ilse Lenaerts, Astrid Bottelbergs
Abstract
model with different doses and/or formulations. Data were analyzed using different ways of ratio calculations: blood concentration at time of sacrifice, total exposure in blood (area under the curve, AUC) and the brain or olfactory bulb concentrations. The IN route was compared to another parenteral route to decide if there is potential direct brain transport. The results show that blood and tissue concentrations and ratios are highly variable and not always reproducible. Potential direct brain delivery was concluded for some compounds, however, sometimes depending on the analysis: using blood levels at sacrifice or AUC could lead to different conclusions. We conclude that a screening model for the evaluation of direct brain transport of small molecules is very difficult to achieve and a conclusion based on a limited number of animals with this variability is questionable.