Synergistic Antimicrobial Activity in Ampicillin Loaded Core‐Shell ZnO@ZIF‐8 Particles

Abstract Combination therapy with the use of nanomaterials and antibiotics is an effective approach to combat increasing antimicrobial resistance. Herein, the synthesis and antimicrobial activity of core‐shell Zinc oxide ‐ Zeolitic Imidazolate Framework‐8 (ZnO@ZIF‐8) particles loaded with ampicillin is reported. The efficacy of the above system has been evaluated against Gram‐negative Escherichia coli ( E. coli ) and Gram‐positive Staphylococcus aureus ( S. aureus ) strains. The entrapment of ampicillin within the ZIF‐8 shell of the particles allowed its controlled and pH‐responsive release under in vitro conditions. Ampicillin loaded ZnO@ZIF‐8 particles have exhibited enhanced antimicrobial activity as reflected by the minimum inhibitory concentration (MIC) values of 12.50 and 48 μg mL −1 against E. coli and S. aureus , respectively. This was also evident by a several‐fold reduction observed in the bacterial population during the time‐kill assays. The values of fractional inhibitory concentration indices (FICI), assessed for different components, have revealed the ZnO@ZIF‐8/ampicillin system inflicts a synergistic activity against E. coli and an additive activity against S. aureus . Cell membrane disruption is attributed to cell death. Finally, cytotoxicity study against mammalian cell lines has indicated the safety profiles of the particles.