A novel ophthalmic latanoprost 0.005% nanoemulsion: a cytotoxicity study

• Published in: Graefe's archive for clinical and experimental ophthalmology Vol. 260; no. 6; pp. 1941 - 1946
• Main Authors: Tau, Julia, Passerini, María Silvia, del Papa, Melina, Aguilar, Alejandro, Berra, Alejandro
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-06-2022; Springer Nature B.V
• Subjects: Annexin V; Antihypertensive Agents - toxicity; Apoptosis; Basic Science; Benzalkonium chloride; Benzalkonium Compounds - metabolism; Benzalkonium Compounds - toxicity; Cell death; Cell proliferation; Cell viability; Cloprostenol - metabolism; Conjunctiva - metabolism; Cytotoxicity; Emulsions; Eye; Flow cytometry; Glaucoma; Glaucoma - metabolism; Humans; Latanoprost - toxicity; Medicine; Medicine & Public Health; Nanoemulsions; Ophthalmic Solutions - toxicity; Ophthalmology; Potassium sorbate; Preservatives; Preservatives, Pharmaceutical - metabolism; Preservatives, Pharmaceutical - toxicity; Propidium iodide; Prostaglandins F, Synthetic - toxicity; Travoprost; Glaucoma; Ocular surface; Toxicity; Nanoemulsion; Latanoprost
• ISSN: 0721-832X; 1435-702X
• DOI: 10.1007/s00417-021-05536-y

Background
Benzalkonium chloride (BAK), the most commonly used preservative in anti-glaucoma eye drops, inflicts damage to the ocular surface. A novel anti-glaucoma formulation that avoids the use of BAK has been developed. The aim of this study was to evaluate the cytotoxicity of this formulation and to compare it with an ophthalmic solution containing BAK.
Methods
Two different latanoprost eye drops were used: one ophthalmic solution (LSc) containing BAK 0.02% and one ophthalmic nanoemulsion (LNe) with a soft preservative (potassium sorbate 0.18%). Human epithelial conjunctival cells were incubated for 15, 30, and 60 min with either LSc or LNe. The cytotoxicity was determined by MTT assay. Cell death was measured by flow cytometry using annexin V–FITC and propidium iodide.
Results
The values of cell viability and proliferation obtained from cells exposed to LNe were between 80 and 90% relative to the control group, whereas values obtained from cells exposed to LSc were around 30% at all study times (
p
 < 0.05 at 15 and 30 min;
p
 < 0.01 at 60 min). The percentage of viable cells decreased significantly when cells were incubated with LSc compared with cells incubated with LNe at all the study times, while the percentage of cells in late apoptosis/necrosis increased significantly in cells exposed to LSc compared to LNe.
Conclusions
The new latanoprost nanoemulsion is significantly less cytotoxic on human conjunctival cells than LSc. These results suggest that the new formulation might be gentler on the eye surface than currently available BAK-preserved latanoprost solutions.