Chitosan-modified polymeric nanoparticles for the nose-to-brain drug delivery of paroxetine: an <i>in vitro</i> and <i>in vivo</i> evaluation

This work focuses on the development of PLGA nanoparticles and their surface modification by chitosan to enhance the mucoadhesive properties and colloidal stability for intranasal delivery. Chitosan-coated paroxetine-loaded PLGA nanoparticles (PAR-CS-PLGA-NPs) were developed and characterized along with <i>in vitro</i> and <i>in vivo</i> evaluation. Particle size of 181.8 nm with a zeta potential of 36.3 mV was obtained. Entrapment efficiency % and drug loading % were 87.5% and 13.4%, respectively. TEM, FTIR, and DSC were also performed. <i>In vitro</i> drug release studies were conducted in phosphate buffered saline (pH 7.4) and simulated nasal fluid (pH 5.5), and sustained release was found until 72 h. Cellular assays on mammalian cells depicted the cell viability to be >60% even at the maximum concentration of PAR-CS-PLGA-NPs and showed significantly higher uptake than PLGA-NPs. Histopathological studies on the nasal epithelium showed no damage or inflammation when treated with PAR-CS-PLGA-NPs. <i>In vivo</i> studies were performed using Swiss albino mice to estimate the drug biodistribution after intranasal delivery of PAR-CS-PLGA-NPs. A significantly increased drug concentration was observed in the mouse brains (<i>p</i> < 0.05). Pharmacodynamics studies of the PAR-CS-PLGA-NPs were carried out by forced swimming test and locomotor activity test, demonstrating improved behavioral analysis parameters (<i>p</i> < 0.05). Thus, intranasal delivery of paroxetine-loaded mucoadhesive chitosan-coated PLGA nanoparticles could be potentially used for the treatment of depression.