Formulation, Evaluation, and Optimization of Viloxazine-Loaded Chitosan Nanoparticles in In-Situ Gel for Nose-to-Brain Delivery in the Effective Management of Depression

Abstract

Depression is a debilitating mental health disorder that necessitates innovative drug delivery strategies for effective management. This study focuses on developing and optimizing viloxazine-loaded chitosan nanoparticles incorporated into an in-situ gel for nose-to-brain delivery to enhance therapeutic outcomes. VXCN-NPs were prepared using the ionic gelation method and optimized using a Box-Behnken statistical design. The optimized formulation demonstrated a mean particle size of 160 nm, entrapment efficiency of 70.1%, and a PDI of 0.4, ensuring uniformity and stability.

The in-situ gel system exhibited optimal pH (5.58), viscosity (65.4 cps), and gelation temperature (31.4 °C), making it suitable for nasal administration. In-vitro release and ex-vivo permeation studies revealed sustained drug release and enhanced permeation through nasal mucosa, achieving an 82% cumulative drug permeation over 8 hours. Stability studies confirmed the formulation's robustness under standard storage conditions for three months.

This novel VXCN-NPs in-situ gel system effectively bypasses the blood-brain barrier, enhancing drug bioavailability and minimizing systemic side effects, thereby presenting a promising platform for nose-to-brain delivery in the treatment of depression and other central nervous system disorders.