Azithromycin: assessment of intrinsic cytotoxic effects on corneal epithelial cell cultures

Rita Mencucci,¹ Domenico E Pellegrini-Giampietro,² Iacopo Paladini,¹ Eleonora Favuzza,¹ Ugo Menchini,¹ Tania Scartabelli<sup>2

1</sup>Department of Specialized Surgical Science – Eye Clinic, ²Department of Health Science Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy

Purpose: To compare the cytotoxic effects of preservative-free azithromycin on corneal epithelial cells in vivo with those of preservative-free netilmicin and levofloxacin, and the preservative benzalkonium chloride (BAK).
Methods: Rabbit corneal epithelial cells in vitro were incubated for 15 minutes or 6 hours with commercially available ophthalmic preservative-free netilmicin 0.3%, levofloxacin 0.3%, or azithromycin 1.5% preparations or different concentrations of unpreserved azithromycin and different concentrations of BAK. Qualitative analysis was undertaken using phase-contrast optics to examine the morphological aspects of cell cultures and quantitative analysis was undertaken by measuring the release of the cytoplasmic enzyme lactate dehydrogenase into the medium immediately and 24 hours after exposure to drugs. Finally, we observed the wound-healing rate of mechanically injured corneal epithelial cells exposed to each antibiotic ophthalmic preparation for 48 hours.
Results: Our results show that both the commercially available unpreserved mono-dose preparation of azithromycin and ophthalmic preparations of azithromycin up to a concentration of 1.5% were virtually devoid of harmful effects under our experimental conditions. This was not significantly different from the results obtained for the other antibiotic preparations (P > 0.05) tested, but was unlike the results obtained for BAK. Azithromycin 1.5% also showed good recovery properties after a mechanical wound test.
Conclusion: Under our experimental conditions, unpreserved azithromycin 1.5% showed a much lower toxicity than BAK and did not interfere with the wound-healing process.

Keywords: macrolides, toxicity, corneal epithelial cell culture, wound healing, preservative, benzalkonium chloride