Smart Delivery of Nalidixic Acid–Curcumin Complex Via Cerium Oxide Nanoparticles for Urinary Tract Infection and its Management

Abstract

Urinary tract infections (UTIs) are highly prevalent among pregnant women, with global incidences projected to exceed 150 million cases annually, resulting in increased hospitalizations and healthcare expenditures. Biofilm formation by uropathogens enhances bacterial resistance, with Escherichia coli as the primary causative agent. This study reports the synthesis and characterization of cerium oxide nanoparticles (CNPs) loaded with a nalidixic acid–curcumin complex (Nla/Cn-CNPs) for targeted antibacterial therapy. The synthesized NPs displayed a predominantly spherical morphology with a mean particle size of 45–60 nm, as confirmed by SEM and TEM analyses. FTIR and UV–Vis spectroscopy verified the successful conjugation of nalidixic acid and curcumin to the CNP surface. In vitro assays demonstrated that Nla/Cn-CNPs exhibited significant antibacterial activity, against E. coli and E. faecalis. The complex also inhibited biofilm formation by up to 76%, surpassing the efficacy of free drugs alone. Antioxidant assays revealed substantial ROS scavenging activity, with up to 68% reduction in intracellular ROS levels in infected cells treated with Nla/Cn-CNPs. Flow cytometry confirmed that treated groups showed a marked decline in ROS-positive populations compared to untreated infected controls. Biocompatibility testing using Vero cell lines showed over 90% cell viability at concentrations up to 400 µg/mL, indicating minimal cytotoxicity. These findings highlight the potential of Nla/Cn-CNPs as a multifunctional nanoplatform for UTI treatment through enhanced antibacterial, antibiofilm, and antioxidant mechanisms. Future directions include In vivo studies to evaluate pharmacokinetics, biodistribution, and therapeutic efficacy, as well as formulation refinement for clinical translation.