title: In vitro and in vivo evaluation of a preservative-free cationic emulsion of latanoprost in corneal wound healing models.
abstract: OBJECTIVE
  Cationic emulsions (CEs), developed as vehicles for lipophilic drugs, have been shown to be safe and effective for the treatment of dry eye. The aim of this study was to investigate the effects of a preservative-free latanoprost 0.005% CE (latanoprost-CE) in in vitro and in vivo models of corneal wound healing.
  
  
  METHODS
  An in vitro wound was made by scraping through a confluent layer of human corneal epithelial cells. Cytotoxicity, cell migration, and proliferation were analyzed after an exposure to phosphate-buffered saline, CE, latanoprost-CE, 0.02% benzalkonium chloride (0.02%BAK), and Xalatan (latanoprost). In vivo, the recovery and integrity of corneal wound healing were assessed in rat eyes instilled twice a day for 5 days with the above treatments after deepithelialization of the superior cornea.
  
  
  RESULTS
  In vitro wound distances decreased at 2 and 24 hours for human corneal epithelial cells exposed to CE, latanoprost-CE, and phosphate-buffered saline, whereas they progressively increased for 0.02%BAK-treated and latanoprost-treated cells. The greater wound closure was associated with a higher number of Ki67-positive cells. In CE- and latanoprost-CE-treated rats, reepithelialization of the cornea was enhanced, restoring normal appearance and function. In contrast, 0.02%BAK or latanoprost delayed corneal healing, induced inflammation, and decreased MUC5-AC expression.
  
  
  CONCLUSIONS
  Both models effectively evaluated the cytotoxicity and dynamic recovery of corneal wound healing, and their correlation supports the potential of the in vitro model as a reliable alternative to in vivo ocular toxicity tests. Both models demonstrated that in the face of corneal injury, CEs favored corneal healing, whereas BAK was deleterious.
authors.affiliation: INSERM, U968, Department of Therapy, Paris, France. lianghongfr@yahoo.fr
authors.forename: Hong
authors.initials: H
authors.lastname: Liang
authors.forename: Christophe
authors.initials: C
authors.lastname: Baudouin
authors.forename: Philippe
authors.initials: P
authors.lastname: Daull
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Garrigue
authors.forename: Ronald
authors.initials: R
authors.lastname: Buggage
authors.forename: Françoise
authors.initials: F
authors.lastname: Brignole-Baudouin
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000633:toxicity*; D001548:Benzalkonium Compounds / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003228:Conjunctiva / Q000187:drug effects / Q000378:metabolism; D003315:Cornea / Q000187:drug effects / Q000378:metabolism; D065306:Corneal Injuries; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004655:Emulsions; D019573:Epithelium, Corneal / Q000187:drug effects / Q000378:metabolism; D005131:Eye Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D000077338:Latanoprost; D008297:Male; D018613:Microscopy, Confocal; D055271:Mucin 5AC / Q000378:metabolism; D011310:Preservatives, Pharmaceutical / Q000633:toxicity*; D011461:Prostaglandins F, Synthetic / Q000633:toxicity*; D051381:Rats; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000959:Antihypertensive Agents; D001548:Benzalkonium Compounds; D004655:Emulsions; D019394:Ki-67 Antigen; C524680:Muc5ac protein, rat; D055271:Mucin 5AC; D011310:Preservatives, Pharmaceutical; D011461:Prostaglandins F, Synthetic; D000077338:Latanoprost