Abstract
Chronic wounds require dual-action therapies capable of managing localized microbial burdens while simultaneously promoting tissue regeneration. Although metronidazole (MTZ)-loaded chitosan/pectin (CS/Pec) polyelectrolyte complex (PEC) nanoparticles have been previously documented, the precise influence of the electrostatic charge ratio on their structure–property relationships and biological performance remains underexplored. In this study, crosslinker-free MTZ-loaded CS/Pec PEC nanoparticles were engineered via spontaneous aqueous electrostatic self-assembly to systematically investigate the effect of the negative-to-positive charge ratio (n-/n+). The findings demonstrate that electrostatic balance fundamentally dictates nanoparticle architecture, mass transport kinetics, and in vitro biological performance. The optimized formulation (n-/n+ = 0.17) yielded a favorable hydrodynamic diameter of 305.16 ± 11.06 nm, limited polydispersity (0.251 ± 0.05), and high colloidal stability (+25.78 ± 2.56 mV). This specific stoichiometric ratio also maximized drug loading, achieving an entrapment efficiency of 68.43 ± 3.15% and a loading capacity of 39.52 ± 2.19%, which were significantly higher than those of all other tested ratios (p 100%, which indicates that the polymeric matrix actively supports cellular metabolism. Furthermore, in vitro scratch assays, the MTZ-loaded PECs reduced the wound gap by 52% within 24 h, a 4- to 5-fold improvement over both the medium control and free MTZ. By establishing a rigorous structure–property relationship through systematic charge-ratio tuning, this study provides a rationally designed, cytocompatible foundation for the development of PEC-based nanocarriers in advanced wound management.