Rotigotine (RTG) is a non-ergoline dopamine agonist and an approved drug for treating Parkinson’s disease. However, its clinical use is limited due to various problems, viz. poor oral bioavailability (max(brain)) compared to intranasal drug suspensions. Further, the intranasal RTG-LCNP significantly reduced the peak plasma drug concentration (Cmax(plasma)) compared to intranasal RTG suspensions. The direct drug transport percentage (DTP (%)) of optimized RTG-LCNP was found to be 97.3%, which shows effective direct nose-to-brain drug uptake and good targeting efficiency. In conclusion, RTG-LCNP enhanced drug brain availability, showing the potential for clinical application.