Formulation and evaluation of azithromycin loaded chitosan nanoparticles for its antibiofilm activity

The present study focused on the formulation and evaluation of azithromycin-loaded chitosan nanoparticles (AZM-CSNPs) to enhance antimicrobial and antibiofilm efficacy. The nanoparticles were prepared by ionic gelation of chitosan with TPP, followed by PAA coating and covalent conjugation using EDC cross-linking to obtain stable CTS/TPP-PAA NPs. Preformulation studies (FTIR and DSC) confirmed drug-polymer compatibility, while physicochemical characterization revealed that the optimized formulation (CNP 1) exhibited a particle size of 287.3 nm, PDI of 0.352, zeta potential of -22.0 mV, and entrapment efficiency of 98.35%. Transmission Electron Microscopy and Scanning Electron Microscopy analyses confirmed spherical, uniformly distributed nanoparticles. In-vitro drug release demonstrated sustained release of 90% over 24 h. The formulation showed enhanced antimicrobial activity against <i>Staphylococcus aureus</i> with a zone of inhibition of 17-21 mm and significant antibiofilm activity, evidenced by 71% biofilm biomass inhibition and 40 µg/mL EPS reduction. Overall, AZM-CSNPs displayed superior performance compared to pure azithromycin, suggesting their potential as an effective nanocarrier system for treating biofilm-associated infections and addressing antibiotic resistance.