Chlorhexidine–Silver Nanoparticle Conjugation Leading to Antimicrobial Synergism but Enhanced Cytotoxicity

This study explored the potential synergism within chlorhexidine–silver nanoparticle conjugates against Influenza type A, Staphylococcus aureus, Escherichia coli, and Candida albicans. Silver nanoparticles (SN) were obtained by the reduction of silver ions with green tea total phenolic extract and conjugated with chlorhexidine (Cx). The particles were characterized by UV-Vis and FTIR spectroscopies, dynamic light scattering, X-ray diffraction, and transmission electron microscopy. A stable negatively charged nano-silver colloid (ζ = −50.01) was obtained with an average hydrodynamic diameter of 92.34 nm. In the presence of chlorhexidine, the spectral data and the shift of the zeta potential to positive values (ζ = +44.59) revealed the successful sorption of the drug onto the silver surface. The conjugates (SN-Cx) demonstrated potentiation in their effects against S. aureus and C. albicans and synergism against E. coli with minimal inhibitory concentrations of SN at 5.5 µg/mL + Cx 8.8 µg/mL. The SN showed excellent virucidal properties, increasing with time, and demonstrated low toxicity. However, the coupling of the cationic chlorhexidine with nano-silver did not reduce its intrinsic cytotoxicity on various cell lines (MDCK, BJ, and A549). The newly synthesized antimicrobial agent exhibited an extended and promising therapeutic spectrum and needs to be further evaluated regarding the designated route of administration in three-dimensional cell models (e.g., nasal, bronchial, dermal, ocular, etc.).