Microfluidic fabrication of rivastigmine-loaded chitosan-hyaluronic acid nanoparticles using 3D-Printed devices

Abstract

This research investigates the combination of 3D printing and microfluidic technologies to create innovative drug delivery systems for neurodegenerative conditions. Fused Deposition Modeling (FDM) was utilized to design and produce four different microfluidic channel configurations (Y-shaped, T-shaped, Baffle, and Staggered Herringbone Micromixers). These channels were used to prepare chitosan-hyaluronic acid polyelectrolyte nanoparticles encapsulating rivastigmine hydrogen tartrate, a therapeutic agent for Alzheimer's disease. SEM and digital imaging confirmed the high structural accuracy and functionality of the fabricated microchannels. By optimizing nanoparticle preparation conditions, particles with consistent size (309.9-476.36 nm), narrow polydispersity index, and high encapsulation efficiency (up to 94.76 ) were achieved. Electrostatic interactions between chitosan, hyaluronic acid, and rivastigmine facilitated nanoparticle formation without covalent bonding. The optimized formulation was obtained using the Staggered Herringbone Micromixers channel, with a flow rate of 1 mL/min, 0.5 w/v chitosan concentration, and 0.25 w/v hyaluronic acid concentration with maximum particle uniformity and drug loading efficiency. In vitro drug release studies demonstrated a biphasic release pattern, with an initial burst phase followed by sustained release over 24 h. This study demonstrates the potential of combining 3D printing and microfluidics for the reproducible, scalable, and cost-effective production of electrostatic nanoparticulate drug delivery systems, offering a promising platform for treating Alzheimer's and other neurodegenerative diseases.