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

Alharbi L, Abalkhail G, Alabrah F, Alsuwayyid F, Alzahrani RR, Farh I, Halwani M, Obaidat AA et al.

Pharmaceuticals (Basel, Switzerland), 2026

Abstract

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…

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