Oleic Acid-Modified Oligochitosan Nanoparticles Preserve Bacteriophage Lytic Activity against Clinical Escherichia coli Isolates from Patients with Cystic Fibrosis

Abstract Cystic fibrosis (CF) lung infections are recurrent and frequently associated with multidrug-resistant bacteria, limiting the efficacy of the currently available antibiotic therapies. Bacteriophages have emerged as a promising alternative; however, their clinical translation is constrained by their limited stability and inefficient delivery within the airway microenvironment. Here, oleic acid-modified oligochitosan (OCS-OA) nanoparticles were developed as controlled-release nanocarriers to promote bacterial clearance during infection. Three OCS-OA formulations (10, 20, and 30% OA substitution) were modified via an amidation reaction and confirmed by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). Surface tension analysis demonstrated the amphiphilic behavior and self-assembly of the modified oligosaccharides into micelle-like nanostructures. The bacteriophage (vB_Eco_K-02) was efficiently encapsulated (>90%), and the resulting formulations were characterized by scanning transmission electron microscopy (STEM), atomic force microscopy (AFM), dynamic light scattering (DLS), and ζ-potential. Formulations prepared with 10 and 20% OCS-OA preserved phage lytic activity against a clinical Escherichia coli strain isolated from CF patients, while the 30% formulation showed reduced activity, suggesting restricted phage release at a higher hydrophobic content.