Corneal epithelial cell viability following exposure to ophthalmic solutions containing preservatives and/or antihypertensive agents

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Abstract

Introduction: This in-vitro study compared the toxicity of bimatoprost 0.01% containing benzalkonium chloride (BAK) 0.02% with other commercial BAK-free or BAK-containing prostaglandin analogs. Methods: Six test solutions were evaluated: travoprost 0.004% with polyquaternium-1 0.001% (PQ), PQ, bimatoprost 0.01% with BAK 0.02%, latanoprost 0.005% with BAK 0.02%, tafluprost 0.0015% preservative free (PF), and BAK 0.02%. Phosphate-buffered saline (PBS) was the live control and 70% methanol was the dead control. Confluent human corneal epithelial cells were incubated with test solutions (diluted 1:5 or 1:10 with PBS) or control solutions for 10 or 25 min, after which cells were fluorescently labeled to distinguish live and dead cells. Data were expressed as a percentage of PBS live-cell fluorescence for automated readouts. Live and dead cells were manually counted for numeric analyses. Results: For 1:5 and 1:10 dilutions using automated readout, cells exposed to bimatoprost with BAK, latanoprost with BAK, and BAK alone demonstrated significant reductions in the live cell signal compared with PBS, travoprost with PQ, and PQ alone (all P < 0.001). They also demonstrated significantly greater toxicity than tafluprost PF for 1:5 dilutions (all P < 0.001) and 1:10 dilutions (P ≤ 0.02), except for 1:10-diluted bimatoprost with BAK (P = 0.41). For 1:5 dilutions using manual cell count, cells exposed to bimatoprost with BAK demonstrated significant reductions in the percentage of live cells compared with PBS (P = 0.02). For 1:10 dilutions using manual cell count, cells exposed to bimatoprost with BAK, latanoprost with BAK, and BAK alone demonstrated significantly greater toxicity than PBS, travoprost with PQ, PQ alone, and tafluprost PF (all P ≤ 0.03). No significant differences were observed among PBS, travoprost with PQ, and PQ alone under any test conditions (P ≥ 0.63). Conclusion: This study demonstrated that BAK-containing solutions, including bimatoprost 0.01% with BAK, were toxic to human corneal epithelial cells, whereas BAK-free solutions showed little to no evidence of toxicity.

Original languageEnglish (US)
Pages (from-to)874-888
Number of pages15
JournalAdvances in Therapy
Volume29
Issue number10
DOIs
StatePublished - Oct 2012

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Benzalkonium Compounds
Ophthalmic Solutions
Antihypertensive Agents
Cell Survival
Epithelial Cells
latanoprost
Phosphates
Cell Count
Synthetic Prostaglandins
polyquaternium 1

Keywords

  • Benzalkonium chloride
  • Bimatoprost
  • Latanoprost
  • Ophthalmology
  • Polyquaternium
  • Preservative
  • Prostaglandin analog
  • Tafluprost
  • Toxicity
  • Travoprost

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Medicine(all)

Cite this

@article{ec26b7bf506e4f1d8a67a6e8b297c99e,
title = "Corneal epithelial cell viability following exposure to ophthalmic solutions containing preservatives and/or antihypertensive agents",
abstract = "Introduction: This in-vitro study compared the toxicity of bimatoprost 0.01{\%} containing benzalkonium chloride (BAK) 0.02{\%} with other commercial BAK-free or BAK-containing prostaglandin analogs. Methods: Six test solutions were evaluated: travoprost 0.004{\%} with polyquaternium-1 0.001{\%} (PQ), PQ, bimatoprost 0.01{\%} with BAK 0.02{\%}, latanoprost 0.005{\%} with BAK 0.02{\%}, tafluprost 0.0015{\%} preservative free (PF), and BAK 0.02{\%}. Phosphate-buffered saline (PBS) was the live control and 70{\%} methanol was the dead control. Confluent human corneal epithelial cells were incubated with test solutions (diluted 1:5 or 1:10 with PBS) or control solutions for 10 or 25 min, after which cells were fluorescently labeled to distinguish live and dead cells. Data were expressed as a percentage of PBS live-cell fluorescence for automated readouts. Live and dead cells were manually counted for numeric analyses. Results: For 1:5 and 1:10 dilutions using automated readout, cells exposed to bimatoprost with BAK, latanoprost with BAK, and BAK alone demonstrated significant reductions in the live cell signal compared with PBS, travoprost with PQ, and PQ alone (all P < 0.001). They also demonstrated significantly greater toxicity than tafluprost PF for 1:5 dilutions (all P < 0.001) and 1:10 dilutions (P ≤ 0.02), except for 1:10-diluted bimatoprost with BAK (P = 0.41). For 1:5 dilutions using manual cell count, cells exposed to bimatoprost with BAK demonstrated significant reductions in the percentage of live cells compared with PBS (P = 0.02). For 1:10 dilutions using manual cell count, cells exposed to bimatoprost with BAK, latanoprost with BAK, and BAK alone demonstrated significantly greater toxicity than PBS, travoprost with PQ, PQ alone, and tafluprost PF (all P ≤ 0.03). No significant differences were observed among PBS, travoprost with PQ, and PQ alone under any test conditions (P ≥ 0.63). Conclusion: This study demonstrated that BAK-containing solutions, including bimatoprost 0.01{\%} with BAK, were toxic to human corneal epithelial cells, whereas BAK-free solutions showed little to no evidence of toxicity.",
keywords = "Benzalkonium chloride, Bimatoprost, Latanoprost, Ophthalmology, Polyquaternium, Preservative, Prostaglandin analog, Tafluprost, Toxicity, Travoprost",
author = "Whitson, {Jess T.} and Petroll, {W. Matthew}",
year = "2012",
month = "10",
doi = "10.1007/s12325-012-0057-1",
language = "English (US)",
volume = "29",
pages = "874--888",
journal = "Advances in Therapy",
issn = "0741-238X",
publisher = "Health Communications Inc.",
number = "10",

}

TY - JOUR

T1 - Corneal epithelial cell viability following exposure to ophthalmic solutions containing preservatives and/or antihypertensive agents

AU - Whitson, Jess T.

AU - Petroll, W. Matthew

PY - 2012/10

Y1 - 2012/10

N2 - Introduction: This in-vitro study compared the toxicity of bimatoprost 0.01% containing benzalkonium chloride (BAK) 0.02% with other commercial BAK-free or BAK-containing prostaglandin analogs. Methods: Six test solutions were evaluated: travoprost 0.004% with polyquaternium-1 0.001% (PQ), PQ, bimatoprost 0.01% with BAK 0.02%, latanoprost 0.005% with BAK 0.02%, tafluprost 0.0015% preservative free (PF), and BAK 0.02%. Phosphate-buffered saline (PBS) was the live control and 70% methanol was the dead control. Confluent human corneal epithelial cells were incubated with test solutions (diluted 1:5 or 1:10 with PBS) or control solutions for 10 or 25 min, after which cells were fluorescently labeled to distinguish live and dead cells. Data were expressed as a percentage of PBS live-cell fluorescence for automated readouts. Live and dead cells were manually counted for numeric analyses. Results: For 1:5 and 1:10 dilutions using automated readout, cells exposed to bimatoprost with BAK, latanoprost with BAK, and BAK alone demonstrated significant reductions in the live cell signal compared with PBS, travoprost with PQ, and PQ alone (all P < 0.001). They also demonstrated significantly greater toxicity than tafluprost PF for 1:5 dilutions (all P < 0.001) and 1:10 dilutions (P ≤ 0.02), except for 1:10-diluted bimatoprost with BAK (P = 0.41). For 1:5 dilutions using manual cell count, cells exposed to bimatoprost with BAK demonstrated significant reductions in the percentage of live cells compared with PBS (P = 0.02). For 1:10 dilutions using manual cell count, cells exposed to bimatoprost with BAK, latanoprost with BAK, and BAK alone demonstrated significantly greater toxicity than PBS, travoprost with PQ, PQ alone, and tafluprost PF (all P ≤ 0.03). No significant differences were observed among PBS, travoprost with PQ, and PQ alone under any test conditions (P ≥ 0.63). Conclusion: This study demonstrated that BAK-containing solutions, including bimatoprost 0.01% with BAK, were toxic to human corneal epithelial cells, whereas BAK-free solutions showed little to no evidence of toxicity.

AB - Introduction: This in-vitro study compared the toxicity of bimatoprost 0.01% containing benzalkonium chloride (BAK) 0.02% with other commercial BAK-free or BAK-containing prostaglandin analogs. Methods: Six test solutions were evaluated: travoprost 0.004% with polyquaternium-1 0.001% (PQ), PQ, bimatoprost 0.01% with BAK 0.02%, latanoprost 0.005% with BAK 0.02%, tafluprost 0.0015% preservative free (PF), and BAK 0.02%. Phosphate-buffered saline (PBS) was the live control and 70% methanol was the dead control. Confluent human corneal epithelial cells were incubated with test solutions (diluted 1:5 or 1:10 with PBS) or control solutions for 10 or 25 min, after which cells were fluorescently labeled to distinguish live and dead cells. Data were expressed as a percentage of PBS live-cell fluorescence for automated readouts. Live and dead cells were manually counted for numeric analyses. Results: For 1:5 and 1:10 dilutions using automated readout, cells exposed to bimatoprost with BAK, latanoprost with BAK, and BAK alone demonstrated significant reductions in the live cell signal compared with PBS, travoprost with PQ, and PQ alone (all P < 0.001). They also demonstrated significantly greater toxicity than tafluprost PF for 1:5 dilutions (all P < 0.001) and 1:10 dilutions (P ≤ 0.02), except for 1:10-diluted bimatoprost with BAK (P = 0.41). For 1:5 dilutions using manual cell count, cells exposed to bimatoprost with BAK demonstrated significant reductions in the percentage of live cells compared with PBS (P = 0.02). For 1:10 dilutions using manual cell count, cells exposed to bimatoprost with BAK, latanoprost with BAK, and BAK alone demonstrated significantly greater toxicity than PBS, travoprost with PQ, PQ alone, and tafluprost PF (all P ≤ 0.03). No significant differences were observed among PBS, travoprost with PQ, and PQ alone under any test conditions (P ≥ 0.63). Conclusion: This study demonstrated that BAK-containing solutions, including bimatoprost 0.01% with BAK, were toxic to human corneal epithelial cells, whereas BAK-free solutions showed little to no evidence of toxicity.

KW - Benzalkonium chloride

KW - Bimatoprost

KW - Latanoprost

KW - Ophthalmology

KW - Polyquaternium

KW - Preservative

KW - Prostaglandin analog

KW - Tafluprost

KW - Toxicity

KW - Travoprost

UR - http://www.scopus.com/inward/record.url?scp=84872098988&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84872098988&partnerID=8YFLogxK

U2 - 10.1007/s12325-012-0057-1

DO - 10.1007/s12325-012-0057-1

M3 - Article

C2 - 23065664

AN - SCOPUS:84872098988

VL - 29

SP - 874

EP - 888

JO - Advances in Therapy

JF - Advances in Therapy

SN - 0741-238X

IS - 10

ER -