title: Comparative in vitro toxicology study of travoprost polyquad-preserved, travoprost BAK-preserved, and latanoprost BAK-preserved ophthalmic solutions on human conjunctival epithelial cells.
abstract: OBJECTIVE
  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).
  
  
  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 (H(2)DCF-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.
authors: Paris, France. francoise.brignole@inserm.fr
authors: Françoise
authors: F
authors: Brignole-Baudouin
authors: Luisa
authors: L
authors: Riancho
authors: Hong
authors: H
authors: Liang
authors: Christophe
authors: C
authors: Baudouin
mesh_terms: D000959:Antihypertensive Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001548:Benzalkonium Compounds / Q000494:pharmacology*; D002470:Cell Survival; D002478:Cells, Cultured; D003008:Cloprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D003228:Conjunctiva / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004338:Drug Combinations; D064420:Drug-Related Side Effects and Adverse Reactions; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D000077338:Latanoprost; D009798:Ocular Hypertension / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009883:Ophthalmic Solutions; D018384:Oxidative Stress / Q000187:drug effects; D011108:Polymers / Q000494:pharmacology*; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D000069557:Travoprost
chemical_list: D000959:Antihypertensive Agents; D001548:Benzalkonium Compounds; D004338:Drug Combinations; D009883:Ophthalmic Solutions; D011108:Polymers; D011310:Preservatives, Pharmaceutical; D011461:Prostaglandins F, Synthetic; D003008:Cloprostenol; D000077338:Latanoprost; C058655:polyquaternium 1; D000069557:Travoprost