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

Alaa Eldeen Yassin; Abdulkareem M Albekairy; Mustafa E Omer; Arwa Almutairi; Yousef Alotaibi; Salem Althuwaini; Osama Aql Alaql; Shahad S Almozaai; Nouf Mohammed Almutiri; Wed Alluhaim; Raghad R Alzahrani; Asma M Alterawi; Majed A Halwani

doi:10.2147/NSA.S438484

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

Nanotechnol Sci Appl. 2023 Dec 21:16:59-72. doi: 10.2147/NSA.S438484. eCollection 2023.

Authors

Alaa Eldeen Yassin^{1

2}, Abdulkareem M Albekairy^{1

3}, Mustafa E Omer⁴, Arwa Almutairi¹, Yousef Alotaibi¹, Salem Althuwaini¹, Osama Aql Alaql¹, Shahad S Almozaai¹, Nouf Mohammed Almutiri¹, Wed Alluhaim^{2

5}, Raghad R Alzahrani^{2

5}, Asma M Alterawi^{6

7}, Majed A Halwani^{1

2}

Affiliations

¹ College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
² King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
³ Pharmaceutical Care Services, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
⁴ Pharmacy Program, College of Health and Sport Sciences, University of Bahrain, Zallaq, Bahrain.
⁵ Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia.
⁶ Department of Pharmaceutics and Center for Pharmaceutical Engineering and Sciences, School of Pharmacy, Virginia Commonwealth University, Richmond, VA, 23298, USA.
⁷ Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.

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; chitosan-coated nanoparticles; ciprofloxacin; differential scanning calorimetry; poly-caprolactone.