Optimized Chitosan Nanoparticles for Enhanced Ciprofloxacin Delivery and Activity Against Resistant Bacteria

Background/Objectives: Ciprofloxacin (CIP) is a fluoroquinolone extensively used in hospital settings for the treatment of bacterial infections; however, this antibiotic requires multiple doses because it has poor absorption, rapid elimination, and is ineffective against resistant bacterial strains. Enhanced delivery efficiency could also be used in the dose-sparing techniques, resulting in better antibiotic efficacy. The aim of this study was to improve CIP-loaded chitosan nanoparticles (NPs) and to evaluate their capacity to enhance the antibacterial response in sensitive and resistant bacterial isolates. Methods: CIP-loaded chitosan nanoparticles were fabricated via ionic gelation using sodium tripolyphosphate (TPP) as a crosslinking agent. Formulation parameters, such as CIP concentration and polymer-to-crosslinker ratios, were optimized. The obtained nanoparticles were evaluated for particle size, polydispersity index, zeta potential, entrapment efficiency, morphology, stability, and in vitro release studies. Antibacterial efficacy was evaluated by determining minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values against standard and ciprofloxacin-resistant clinical isolates. Results: Successful optimization of these formulations allowed the preparation of stable nanoparticles that ranged from 38.39 to 115.07 nm, highlighting the role of both the formulation composition and polymer-to-crosslinker ratios on the size of the nanoparticles. The formulation exhibits a drug entrapment efficiency of 84.1% and uniform particulate size (38.39 ± 0.63 nm), which were optimized due to the polymer and crosslinker ratios. These nanoparticles showed a slow release of the drug over 220 h, and minimal size instability was noted after 28 days. Encapsulation of CIP resulted in enhanced antibacterial activity, yielding 2–4-fold reductions in MIC and MBC values against methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa resistant strains, compared with free CIP. Conclusions: Optimized CIP-loaded chitosan nanoparticles demonstrated improved antibacterial efficacy against resistant strains and good drug delivery properties. These findings highlight the potential of chitosan-based nanocarrier systems to improve the performance of CIP and antibiotic delivery dose-sparing antibiotic strategies.