Issue 3, 2025

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

Abstract

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 in vitro and in vivo 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. In vitro 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. In vivo 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 (p < 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 (p < 0.05). Thus, intranasal delivery of paroxetine-loaded mucoadhesive chitosan-coated PLGA nanoparticles could be potentially used for the treatment of depression.

Graphical abstract: Chitosan-modified polymeric nanoparticles for the nose-to-brain drug delivery of paroxetine: an in vitro and in vivo evaluation

Supplementary files

Article information

Article type
Paper
Submitted
14 Oct 2024
Accepted
22 Nov 2024
First published
06 Dec 2024

Nanoscale, 2025,17, 1687-1702

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

S. Sharma, P. Gauba, A. Tyagi and S. Dang, Nanoscale, 2025, 17, 1687 DOI: 10.1039/D4NR04250F

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