Intranasal sertraline for the investigation of nose-to-brain delivery to mitigate systemic exposure

Abstract

Antenatal depression, or depression during pregnancy, is a common psychiatric disorder and poses significant risks to both the mother and the fetus. Despite these risks, it is frequently left untreated due to fears of side effects caused by antidepressant medications which cross through the placental barrier. It is therefore desirable to develop formulation strategies to mitigate systemic exposure to relevant drug molecules while maintaining their psychotropic efficacy. In this work, we develop formulations of sertraline, a common antidepressant, to target delivery to the brain through intranasal administration. Formulation engineering enables successful solubilization of sertraline at high concentrations and our lead formulation remains stable at room temperature for months. Using mice, we compare sertraline biodistribution following intranasal administration and standard oral administration. Intranasal administration of our drug product candidate provides comparable brain exposure at half the dose compared to oral treatment and lowers the maximum plasma exposure. These findings suggest that intranasal administration may provide selectivity for drug exposure in the central nervous system over systemic exposure.