Optimization of Rasagiline Mesylate-Loaded Polycaprolactone Nanoparticles for Intranasal Delivery Using Box–Behnken Design

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss, leading to impaired motor and cognitive functions. Rasagiline Mesylate, although therapeutically effective, suffers from low oral bioavailability due to extensive first-pass metabolism and short half-life. The present study aimed to develop and optimize Polycaprolactone (PCL) nanoparticles loaded with Rasagiline Mesylate for intranasal delivery to enhance brain targeting and prolong therapeutic action. Nanoparticles were prepared using a modified nanoprecipitation technique and optimized through Box–Behnken Design (BBD) using Design Expert® 7.0 software. Polymer concentration (A), organic phase volume (B), and surfactant concentration (C) were selected as independent variables, while particle size and entrapment efficiency served as response parameters. ANOVA confirmed the significance of the quadratic model for both responses, with minimal lack of fit. The optimized formulation (Polymer: 232.6 mg; Organic phase: 9.2 ml; Surfactant: 0.59%) exhibited a desirability of 1.0, demonstrating excellent agreement between predicted and experimental responses. Results suggest that intranasal Rasagiline-loaded PCL nanoparticles provide a promising strategy for enhanced brain delivery in PD management by bypassing hepatic metabolism and sustaining drug release.

Keywords: Rasagiline Mesylate, Polycaprolactone (PCL) Nanoparticles, Intranasal Delivery, Box–Behnken Design, Optimization, Entrapment Efficiency, Particle Size, Parkinson’s Disease.