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

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

Int J Mol Sci. 2023 Feb 25;24(5):4532. doi: 10.3390/ijms24054532.

Authors

Mohammad Zaidur Rahman Sabuj¹, Flavia Huygens², Kirsten M Spann³, Abdullah A Tarique⁴, Tim R Dargaville⁵, Geoffrey Will⁶, Md Abdul Wahab⁶, Nazrul Islam^{1

3}

Affiliations

¹ Pharmacy Discipline, School of Clinical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD 4000, Australia.
² School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD 4000, Australia.
³ Centre for Immunology and Infection Control (CIIC), Faculty of Health, Queensland University of Technology, Brisbane, QLD 4000, Australia.
⁴ Child Health Research Centre (CHRC), The University of Queensland, Brisbane, QLD 4101, Australia.
⁵ School of Chemistry and Physics, Faculty of Science, Queensland University of Technology, Brisbane, QLD 4000, Australia.
⁶ School of Mechanical, Medical and Process Engineering, Faculty of Science, Queensland University of Technology, Brisbane, QLD 4000, Australia.

Abstract

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.

Keywords: antibiotic resistance; antimicrobial agents; bactericidal effects; cytotoxicity; digestibility; inhalable formulation; nanoparticles; poly(2-ethyl-2-oxazoline); zinc oxide.

MeSH terms

Anti-Bacterial Agents / pharmacology
Ciprofloxacin / pharmacology
Humans
Metal Nanoparticles* / chemistry
Microbial Sensitivity Tests
Nanoparticles* / chemistry
Pulmonary Disease, Chronic Obstructive*
Spectroscopy, Fourier Transform Infrared
Zinc Oxide* / chemistry

Substances

Ciprofloxacin
Zinc Oxide
poly(2-ethyl-2-oxazoline)
Anti-Bacterial Agents

Grants and funding

This research was supported by the Research Training Program (RTP) Scholarship to Mohammad Zaidur Rahman Sabuj granted by the Australian Government through the Queensland University of Technology (QUT).