Formulation and Optimization of Imeglimin-Loaded Nanoparticles Using Central Composite Design

Type 2 diabetes mellitus (T2DM) is increasing as a worldwide health issue. Imeglimin, a first-in-class oral antidiabetic compound, exerts potential therapeutic activities via several mechanisms, including enhanced mitochondrial function and glucose-stimulated insulin secretion. Despite this, it is still a challenge to increase its oral bioavailability. The purpose of this work was to prepare and optimize Imeglimin-loaded polymeric nanoparticles (IG-PNs) based on chitosan and sodium alginate to enhance entrapment and extended release of the drug for oral delivery. IG-PNs were synthesized through ionotropic gelation and were optimized through a Central Composite Rotatable Design (CCRD). The influence of chitosan and sodium alginate concentration, and stirring speed, was tested on particle size (PS) and entrapment efficiency (EE). The characterization involved dynamic light scattering, zeta potential, scanning electron microscopy, and in vitro release studies. The optimized formulation had a particle size of 126.75 ± 2.39 nm, PDI of 0.228 ± 0.040, and EE of 85.50 ± 5.87%. The zeta potential was −12.8 ± 2.42 mV, and SEM micrographs revealed spherical, uniform particles. Release studies in vitro revealed 80.79 ± 7.33% cumulative release in PBS (pH 7.4) and 14.62 ± 1.87% in 0.1 N HCl, and release kinetics were best described by Korsmeyer-Peppas and zero-order models, respectively. The optimized IG-PNs indicated improved drug entrapment and controlled release, indicating better oral delivery promise for Imeglimin. These results justify more preclinical and clinical investigation.