Cytotoxic and Bactericidal Effects of Inhalable Ciprofloxacin-Loaded Poly(2-ethyl-2-oxazoline) Nanoparticles with Traces of Zinc Oxide

Mohammad Zaidur Rahman Sabuj; Flavia Huygens; Kirsten M. Spann; Abdullah A. Tarique; Tim R. Dargaville; Geoffrey Will; Md Abdul Wahab; Nazrul Islam

doi:10.3390/ijms24054532

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Cytotoxic and Bactericidal Effects of Inhalable Ciprofloxacin-Loaded Poly(2-ethyl-2-oxazoline) Nanoparticles with Traces of Zinc Oxide

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Cytotoxic and Bactericidal Effects of Inhalable Ciprofloxacin-Loaded Poly(2-ethyl-2-oxazoline) Nanoparticles with Traces of Zinc Oxide

Mohammad Zaidur Rahman Sabuj, Flavia Huygens, Kirsten M. Spann, Abdullah A. Tarique, Tim R. Dargaville, Geoffrey Will, Md Abdul Wahab and Nazrul Islam

International Journal of Molecular Sciences, Vol.24(5), pp.1-23

2023

DOI: https://doi.org/10.3390/ijms24054532

PMID: 36901963

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Abstract

antimicrobial agents

antibiotic resistance

bactericidal effects

cytotoxicity

digestibility

inhalable formulation

nanoparticles

poly(2-ethyl-2-oxazoline)

zinc oxide

The bactericidal effects of inhalable ciprofloxacin (CIP) loaded-poly(2-ethyl-2-oxazoline) (PEtOx) nanoparticles (NPs) with traces of zinc oxide (ZnO) were investigated against clinical strains of the respiratory pathogens Staphylococcus aureus and Pseudomonas aeruginosa. CIP-loaded PEtOx NPs retained their bactericidal activity within the formulations compared to free CIP drugs against these two pathogens, and bactericidal effects were enhanced with the inclusion of ZnO. PEtOx polymer and ZnO NPs did not show bactericidal activity alone or in combination against these pathogens. The formulations were tested to determine the cytotoxic and proinflammatory effects on airway epithelial cells derived from healthy donors (NHBE), donors with chronic obstructive pulmonary disease (COPD, DHBE), and a cell line derived from adults with cystic fibrosis (CFBE41o-) and macrophages from healthy adult controls (HCs), and those with either COPD or CF. NHBE cells demonstrated maximum cell viability (66%) against CIP-loaded PEtOx NPs with the half maximal inhibitory concentration (IC50) value of 50.7 mg/mL. CIP-loaded PEtOx NPs were more toxic to epithelial cells from donors with respiratory diseases than NHBEs, with respective IC50 values of 0.103 mg/mL for DHBEs and 0.514 mg/mL for CFBE41o- cells. However, high concentrations of CIP-loaded PEtOx NPs were toxic to macrophages, with respective IC50 values of 0.002 mg/mL for HC macrophages and 0.021 mg/mL for CF-like macrophages. PEtOx NPs, ZnO NPs, and ZnO-PEtOx NPs with no drug were not cytotoxic to any cells investigated. The in vitro digestibility of PEtOx and its NPs was investigated in simulated lung fluid (SLF) (pH 7.4). The analysed samples were characterized using Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), and UV-Vis spectroscopy. Digestion of PEtOx NPs commenced one week following incubation and was completely digested after four weeks; however, the original PEtOx was not digested after six weeks of incubation. The outcome of this study revealed that PEtOx polymer could be considered an efficient drug delivery carrier in respiratory linings, and CIP-loaded PEtOx NPs with traces of ZnO could be a promising addition to inhalable treatments against resistant bacteria with reduced toxicity.

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Title: Cytotoxic and Bactericidal Effects of Inhalable Ciprofloxacin-Loaded Poly(2-ethyl-2-oxazoline) Nanoparticles with Traces of Zinc Oxide
Authors: Mohammad Zaidur Rahman Sabuj (Author) - Queensland University of Technology
Flavia Huygens (Author) - Queensland University of Technology
Kirsten M. Spann (Author) - Queensland University of Technology
Abdullah A. Tarique (Author) - The University of Queensland
Tim R. Dargaville (Author) - Queensland University of Technology
Geoffrey Will (Author) - Queensland University of Technology
Md Abdul Wahab (Author) - Queensland University of Technology
Nazrul Islam (Corresponding Author) - Queensland University of Technology
Publication details: International Journal of Molecular Sciences, Vol.24(5), pp.1-23
Publisher: MDPI AG
Date published: 2023
DOI: 10.3390/ijms24054532
ISSN: 1422-0067; 1661-6596
PMID: 36901963
Copyright note: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Data Availability: Data are contained within the article.
Organisation Unit: School of Science, Technology and Engineering
Language: English
Record Identifier: 99737873702621
Output Type: Journal article

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Web Of Science research areas: Biochemistry & Molecular Biology; Chemistry, Multidisciplinary

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