title: Analysis of the transport of and cytotoxic effects for nalbuphine solution in corneal cells.
abstract: OBJECTIVE
  To assess the in vitro effects of various nalbuphine concentrations on viability and wound healing ability of corneal cells and potential drug transport through the corneal epithelium.
  
  
  METHODS
  Cultured canine and human corneal epithelial cells (CECs) and cultured canine corneal stromal fibroblasts.
  
  
  METHODS
  CECs and stromal fibroblasts were exposed to nalbuphine (concentration of solutions ranged from 0% to 1.2%) for up to 30 minutes, and viability was assessed with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. A standard scratch test technique was used. Wound healing of CECs and stromal fibroblasts was evaluated following treatment with nalbuphine solutions < 0.1%. Liquid chromatography-mass spectrometry-mass spectrometry analysis was used to evaluate drug transport across a monolayer and a multilayer of human CECs.
  
  
  RESULTS
  A progressive decrease in viability was detected in canine CECs for all nalbuphine treatment groups, whereas treatment with only 0.5% or 1.2% nalbuphine significantly reduced corneal stromal fibroblast viability, compared with results for control cells. Within 24 hours, treatment with 0.1% nalbuphine solution significantly altered the healing rate of both canine CECs and stromal fibroblasts. Continuous increases in transport rates of nalbuphine were detected with time for both the monolayer and multilayer of human CECs.
  
  
  CONCLUSIONS
  In vitro, nalbuphine potentially could penetrate through corneal tissue, but it may cause damage to the corneal epithelium and stromal fibroblasts. Therefore, nalbuphine potentially may impair corneal wound healing.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Spatola
authors.forename: Mirunalni
authors.initials: M
authors.lastname: Thangavelu
authors.forename: Vijayasaradhi
authors.initials: V
authors.lastname: Upadhyayula
authors.forename: Seungsoo
authors.initials: S
authors.lastname: Lee
authors.forename: Mitch A
authors.initials: MA
authors.lastname: Phelps
authors.forename: Heather L
authors.initials: HL
authors.lastname: Chandler
mesh_terms: D000287:Administration, Topical; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003319:Corneal Stroma / Q000166:cytology / Q000187:drug effects*; D004285:Dogs; D019573:Epithelium, Corneal / Q000166:cytology / Q000187:drug effects*; D015353:Eye Enucleation / Q000662:veterinary; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D009266:Nalbuphine / Q000008:administration & dosage / Q000494:pharmacology*; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D009266:Nalbuphine