Antimycotic Activity of Ozonized Oil in Liposome Eye Drops against Candida spp.

Abstract

Purpose This study aims to investigate the antifungal activity and mechanism of action of ozonized oil eye drops in liposomes (Ozodrop), commercialized as eye lubricant for the treatment of dry eye syndrome and eye inflammation. The activity was tested against four clinical Candida species: C albicans, C glabrata, C krusei , and C orthopsilosis . Methods The antifungal activity of the eye drop solution was ascertained by microdilution method in accordance with EUCAST obtaining the minimum inhibitory concentration for Ozodrop. The mechanism of action was further investigated in C albicans by measuring cell vitality, intracellular reactive oxygen species production, levels of cellular and mitochondrial (∆Ψ m ) membrane potential, and the extent of membrane lipid peroxidation. Results All Candida isolates were susceptible to Ozodrop with minimum inhibitory concentration values ranging from 0.195% (v/v) for C glabrata to 6.25% (v/v) for C orthopsilosis . After 1 hour of exposure at the minimum inhibitory concentration value about 30% of cells were killed, reaching about 70% at the highest Ozodrop value. After Ozodrop exposure, C albicans showed cell membrane depolarization, increased levels of lipid peroxidation, depolarized ∆Ψ m , and increased reactive oxygen species generation. Conclusions The significant increases in reactive oxygen species production cause the accumulation of reactive oxygen species-associated damages leading to progressive Candida cell dysfunction. Translational Relevance The antifungal activity of Ozodrop was demonstrated at concentrations several times lower than the concentration that can be retrieved in ocular surface after its application. The antifungal activity of the eye drops Ozodrop would represent an interesting off-label indication for a product basically conceived as an eye lubricant.

Topical Liposomal Ozonated Oil in Complicated Corneal Disease: A Report on Three Clinical Cases

“…Of these, liposomal ozonated oil has shown antiseptic and reparative properties and can be proposed for the prevention and treatment of acute and chronic local infections, as an alternative to topical antimicrobial agents, on account of its antibacterial, antifungal and antiviral properties. [4][5][6] Liposomal ozonated oil can therefore be a useful alternative for countering the widespread and indiscriminate use of antibiotics, which has led to the emergence of bacterial resistance, especially in Staphylococci sp. Moreover, topical ozonated oil was seen to accelerate acute cutaneous wound repair in Guinea pig models by promoting collagen synthesis and fibroblast proliferation at the injury site.…”

“…Eye drops containing ozone were recently used in the management of ocular surface infection caused by bacteria, viruses and fungi, [4][5][6] and a specific formulation containing liposomal ozonated sunflower oil (Ozodrop ® , FB Vision, San Benedetto del Tronto, Italy) that is well tolerated by the conjunctival mucosa and ocular surface has been developed. 7 The most frequently diagnosed anterior segment conditions are uveitis, corneal abrasion, corneal ulcer, Meibomian gland dysfunction, dry eye, blepharitis, punctate epithelial erosions, conjunctivitis and epidemic keratoconjunctivitis.…”

“… 3 Ozone’s antimicrobial, antifungal, and antiviral properties are well-known, as is its ability to prevent the development of antimicrobial resistance and allergic reactions. 4 There has consequently been an increase in the use of ozonated oil in clinical practice for the treatment of a number of infectious and inflammatory conditions, including skin diseases, gum disease and diabetic foot ulcers.…”

“…Eye drops containing ozone were recently used in the management of ocular surface infection caused by bacteria, viruses and fungi, 4–6 and a specific formulation containing liposomal ozonated sunflower oil (Ozodrop ® , FB Vision, San Benedetto del Tronto, Italy) that is well tolerated by the conjunctival mucosa and ocular surface has been developed. 7 …”

Lactobacillus sakei Pro-Bio65 Reduces TNF-α Expression and Upregulates GSH Content and Antioxidant Enzymatic Activities in Human Conjunctival Cells

“…Changes in the ΔΨ m , in samples incubated for 2 hours with L.SK , were analyzed using the JC-1 lipophilic cation dye, as previously reported. 36 Samples (1 × 10 6 cells) were incubated with 3 µM JC-1 (Molecular Probes, Eugene, OR, USA), for 30 minutes at 37°C in a humidified atmosphere, collected, washed in PBS, and analyzed by flow cytometry. The fluorescence signals of JC-1 monomers and aggregates were detected through the FL-1 (525 ± 5 nm bandpass filter) and FL-2 channels (575 ± 5 nm bandpass filter).…”