Antimicrobial resistance is a critical public health issue in the world which is now challenging rnthe effectiveness of drugs and successful treatment of infectious disease as well as povertyrneradication due to its significant financial burden. Urinary tract infection is the most commonrnnosocomial infection which is mostly caused by Escherichia coli. Like other infectious disease,rnits management has become challenging due to antimicrobial resistance. To tackle this problemrnresearchers develop various suitable alternatives including inorganic nanoparticles like zincrnoxide nanoparticles (ZnONPs) which are known for their antimicrobial activity, and use of thesernnanoparticles for the delivery of antibiotics to benefit from the synergetic effect against resistantrnmicrobials. Therefore, our study aimed to synthesize ZnONPs using water extracts of MoringarnStenopetala leaf which is an endemic plant to Ethiopia, north Kenya and east Somali.rnNanoparticles were characterized using ultraviolet-visible spectroscopy, X-ray diï¬€ractionrn(XRD), dynamic light scattering (DLS), scanning electron microscope (SEM), differentialrnscanning calorimetry-thermogravimetric (DSC-TGA) analysis and fourier transform infraredrnspectroscopy (FTIR). Then, nanoparticles were loaded with ciprofloxacin and characterizedrnusing ultraviolet-visible spectroscopy, DLS and FTIR to confirm the effective loading ofrnciprofloxacin on nanoparticles. Nanoparticles were also evaluated for their drug deliveryrnpotential. The drug loading content and drug entrapment efficacy were 49.1% and 96.5 %,rnrespectively. The drug loaded nanoparticles were also evaluated for their drug releasing behaviorrnat four different pH conditions (1.2, 6.0, 6.8 and 7.4 to simulate gastric, E.coli infected urinaryrntract, intestine and blood pH values, respectively). The result revealed that the loadedrnciprofloxacin were efficiently released from ZnONPs at the site of E.coli infected uroepitheliumrnenvironment in a sustained manner but with instant release in acidic pH due to the higherrnsolubility of the drug and the nanoparticle in acidic pH. Finally, the antimicrobial activity ofrnZnONPs and ciprofloxacin loaded NPs was evaluated and compared with ciprofloxacin alone byrnthe disc diï¬€usion method. Accordingly, the drug loaded ZnONPs showed promising resultrnagainst ciprofloxacin resistant E.coli and significantly enhanced the antibacterial activity ofrnciprofloxacin against this pathogen compared with ciprofloxacin and the unloaded NPs.