Antibiotic-resistant bacteria may result in serious infections which are difficult to treat. In addition, the poor antibiotic pipeline has contributed to the crisis. Recently, a complex of furosemide and silver (Ag-FSE) has been reported as a potential antibacterial agent. However, its poor aqueous solubility is limiting its activity. The purpose of this study was to encapsulate Ag-FSE into chitosan nanoparticles (CSNPs) and evaluate antibacterial efficacy. Ag-FSE CSNPs were prepared using an ionic gelation technique. The particle size, polydispersity index, and zeta potential of Ag-FSE CSNPs were 197.1 ± 3.88 nm 0.234 ± 0.018 and 36.7 ± 1.78 mV, respectively. Encapsulation efficiency was 66.72 ± 4.14%. In vitro antibacterial activity results showed that there was 3- and 6-fold enhanced activity with Ag-FSE CSNPs against E. coli and S. aureus, respectively. Results also confirmed that Ag-FSE CSNPs showed ~44% release within 4 h at pH 5.5 and 6.5. Moreover, release from the CSNPs was sustained with a cumulative release of ~75% over a period of 24 h. In conclusion, encapsulation of Ag-FSE into CSNPs resulted in significant improvement of antibacterial efficacy with a sustained and pH-sensitive release. Therefore, Ag-FSE CSNPs can be considered as a potential novel antibacterial agent against bacterial infections.

Silver (Ag) complexes of drugs and their nanosystems have great potential as antibacterials. Recently, an Ag complex of furosemide (Ag–FSE) has shown to be a promising antimicrobial. However, poor solubility of Ag–FSE could hamper its introduction into clinics. Therefore, the authors developed a nanosuspension of Ag–FSE (Ag–FSE_NS) for its solubility and antibacterial activity enhancement. The aim of this study was to introduce a novel nanoantibiotic with enhanced antibacterial efficacy. Ag–FSE_NS was prepared by precipitation–ultrasonication technique. Size, polydispersity index (PI) and zeta potential (ZP) of prepared Ag–FSE_NS were measured by dynamic light scattering, whereas surface morphology was determined using scanning electron microscopy (SEM). In vitro antibacterial activity was evaluated against Staphylococcus aureus , Escherichia coli and Pseudomonas aeruginosa using broth microdilution method. Size, PI and ZP of optimised Ag–FSE_NS1 were 191.2 ± 19.34 nm, 0.465 ± 0.059 and −55.7 ± 8.18 mV, respectively. SEM revealed that Ag–FSE_NS1 particles were rod or needle‐like with smooth surfaces. Saturation solubility of Ag–FSE in NS increased eight‐fold than pure Ag–FSE. Ag–FSE_NS1 exhibited two‐fold and eight‐fold enhancements in activity against E. coli and S. aureus , respectively. The results obtained showed that developed Ag–FSE_NS1 holds a promise as a topical antibacterial.