Chitosan-Coated Azithromycin/Ciprofloxacin-Loaded Polycaprolactone Nanoparticles: A Characterization and Potency Study

Abstract

Purpose

Antimicrobial resistance is a major health hazard worldwide. Combining azithromycin (AZ) and ciprofloxacin (CIP) in one drug delivery system was proposed to boost their antibacterial activity and overcome resistance. This study aims to improve azithromycin and ciprofloxacin activity by co-encapsulating them inside chitosan-coated polymeric nanoparticles and evaluating their antibacterial activity.

Methods

The double emulsion method was employed to co-encapsulate AZ/CIP inside chitosan-coated polymeric nanoparticles. The formulations were evaluated for their nanoparticle size, size distribution, and zeta potential. Differential scanning calorimetry (DSC) analysis characterized the formula’s thermal sustainability. Encapsulation efficiency was measured by HPLC and spectrophotometric analysis. Morphological studies used the Transmission Electron Microscopy (TEM). The in vitro release profiles of both AZ and CIP were monitored utilizing the dialysis membrane bag method. The micro-dilution assay assessed the antimicrobial activity against a clinical isolate of Klebsiella pneumoniae.

Results

The prepared AZ/CIP-poly-caprolactone nanoparticles were spherical; their size range was 184.0 ± 3.3–190.4 ± 5.6 nm and had high size uniformity (poly-dispersity index below 0.2). The zeta potential ranged from −21.2 ± 2.4 to −27.0 ± 2.5 mV, while chitosan-coated nanoparticles showed a positive zeta potential value ranging from 8 to 11 mV. The thermal study confirmed the amorphous state of both antibiotics inside the nanoparticles. The results of the in vitro release study indicated a slow and uniform rate of release for both drugs extended over 4-days, with a faster rate in the case of AZ. The MIC values reported for both chitosan-coated NP have been tremendously reduced by at least 15 folds of pure CIP and more than 60 folds of pure AZ.

Conclusion

The co-encapsulation of AZ/CIP into chitosan-coated polymeric nanoparticles has been successfully achieved. The produced particles showed many beneficial attributes of uniform particle sizes below 200 nm and high zeta potential values. Chitosan-coated polymeric nanoparticles extensively enhanced the antibacterial activity of both AZ/CIP against bacteria.

Keywords:

• azithromycin
• ciprofloxacin
• poly-caprolactone
• chitosan-coated nanoparticles
• differential scanning calorimetry

Acknowledgments

This work was funded by two grants from King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia (Grants No. SP19/235/R) and (SP19/237/R). The funding agency had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Disclosure

The authors report no conflicts of interest in this work.