Comparative In Vitro Toxicology Study of Travoprost Polyquad-preserved, Travoprost BAK-preserved, and Latanoprost BAK-preserved Ophthalmic Solutions on Human Conjunctival Epithelial Cells

Abstract

Purpose: To compare the toxicological profile of a new formulation of travoprost 0.004% ophthalmic solution (travoprost PQ), containing the preservative polyquaternium-1(PQ, polyquad), with the commercially available formulation of benzalkonium chloride (BAK)-preserved travoprost 0.004% ophthalmic solution (travoprost BAK) and BAK-preserved latanoprost 0.005% ophthalmic solution (latanoprost BAK).Materials and Methods: Human conjunctival epithelial cells were incubated with phosphate-buffered saline (PBS), BAK 0.015%, BAK 0.020%, PQ 0.001%, travoprost PQ preserved with PQ 0.001%, travoprost preserved with BAK 0.015%, or latanoprost preserved with BAK 0.020%. Six toxicological assays were used to assess: cell viability (neutral red, Alamar blue), apoptosis (YO-PRO-1, Hoechst 33342), and oxidative stress (H2DCF-DA, hydroethidine). Apoptosis and oxidative stress were each reported according to cell viability as observed with neutral red and Alamar blue for a total of 10 analyses per treatment depending on the cell viability test used to interpret apoptosis and oxidative stress responses.Results: There were no significant differences in toxicity between cells exposed to PBS and cells exposed to travoprost PQ (10/10 analyses) or PQ 0.001% (9/10 analyses). Ten out of 10 analyses revealed that travoprost PQ produced significantly less cytotoxicity than latanoprost BAK (p < 0.0001). Travoprost PQ produced significantly better cell viability and less apoptosis than travoprost BAK (6/6 analyses, p < 0.0001). Travoprost BAK was significantly less cytotoxic than latanoprost BAK in 7 of 10 analyses (p < 0.0001). All 10 of the analyses revealed that BAK 0.015%, BAK 0.020%, and latanoprost BAK produced significantly more cytotoxicity than PBS (p < 0.0001). Travoprost BAK was significantly less cytotoxic than its corresponding BAK 0.015% preservative solution in 9 of 10 analyses (p < 0.0001).Conclusions: A panel of in vitro toxicity analyses supports the safety of travoprost PQ. Travoprost PQ may be better for ocular surface health than BAK-preserved formulations of latanoprost or travoprost but clinical studies are required to validate these comparisons.