Corneal toxicity studies in rabbits and dogs with hydroxyethyl cellulose and benzalkonium chloride

Durand-Cavagna, G.

doi:10.1016/0272-0590(89)90286-8

Cited by 20 publications

(4 citation statements)

References 21 publications

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“…The in vivo toxicity of BAC results in inflammation and congestion, tear film instability (i.e., a decrease of break time for tears), loss of conjunctival goblet cells, corneal epithelial desquamation, erosions, ulceration and corneal neovascularization, as well as many other signs in mice [3,10], rats [11], cats [12], rabbits [13,14], guinea pigs [15], and dogs [16]. However, few experimental studies have explored the mechanisms of BAC-induced damage to the ocular surface in addition to its detergent properties.…”

Section: Introductionmentioning

confidence: 99%

A Comparison of the Effects of Benzalkonium Chloride on Ocular Surfaces between C57BL/6 and BALB/c Mice

Yang

Zhang

Liu

et al. 2017

IJMS

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Models of benzalkonium chloride (BAC)-induced ocular disruption have been created and are widely used in various animals. This study aimed to compare the effects of BAC on the ocular surfaces of C57BL/6 and BALB/c mice. C57BL/6 and BALB/c mice were treated separately with BAC eye-drops at different concentrations. Eyes were evaluated by scoring epithelial disruption, corneal opacity and neovascularization in vivo, and by histological assays with hematoxylin/eosin (H/E) and periodic acid-Schiff stainings and by determining the expression of inflammatory factors in vitro on Days 7 and 14. The in vivo corneal epithelial disruption, corneal edema/opacity and neovascularization, which were in accordance with the results of the H/E staining and peaked at Day 7, were observed in a dose-dependent manner in the BAC-treated mice, with more severe signs in the C57BL/6 mice than the BALB/c mice. The loss of conjunctival goblet cells in the conjunctivas and the increasing expression of monocyte chemoattractant protein 1 (MCP-1), growth-regulated protein alpha (GROa) and macrophage inflammatory protein-1 alpha (MIP-1a) in the corneas were found in a dose-dependent manner in both strains of mice. Topical application of BAC can dramatically disrupt the ocular surfaces of C57BL/6 and BALB/c mice, and the disruptions were much more severe in the C57BL/6 mice that received high doses of BAC.

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Section: Introductionmentioning

confidence: 99%

A Comparison of the Effects of Benzalkonium Chloride on Ocular Surfaces between C57BL/6 and BALB/c Mice

Yang

Zhang

Liu

et al. 2017

IJMS

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“…Ciprofloxacin‐ and tobramycin‐containing solutions were used because they were the only commercially available products at the time of the study. The preservative included in both of the evaluated solutions (i.e., benzalkonium chloride) has also been demonstrated to induce morphologic changes in canine corneal epithelial cells and delay cellular migration in a concentration and time‐dependent manner in vitro ; however, no adverse effects were observed in a separate in vivo canine study evaluating benzalkonium chloride's toxicity on intact corneal epithelium when administered alone and in combination with a viscosity‐enhancing agent 12,13 …”

Section: Discussionmentioning

confidence: 99%

Efficacy of two chondroitin sulfate ophthalmic solutions in the therapy of spontaneous chronic corneal epithelial defects and ulcerative keratitis associated with bullous keratopathy in dogs

Ledbetter

Munger²,

Ring³

et al. 2006

Veterinary Ophthalmology

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Topical therapy with an antimicrobial-chondroitin sulfate ophthalmic solution combined with manual debridement of nonadherent epithelium compares favorably with other published medical and surgical therapies for SCCED; however, these compounds are only equivocally more effective than therapy with manual debridement alone. These solutions appear to be ineffective in the treatment of ulcerative keratitis associated with bullous keratopathy. The significance of the two cases of corneal stromal abscessation is unknown at this time and warrants further investigation.

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“…It should be noted that the toxicity of preservatives may incidentally be enhanced by viscosity-building agents present in eyedrops. For instance, corneal epithelial damage has been observed when the thickening agent hydroxyethylcellulose is used with BAK, although no such effect was observed when either excipient was used alone [49]. Similarly, punctal plugs, commonly used in DED therapy to reduce tear drainage, can increase the exposure to toxic preservatives enhancing their detrimental effects.…”

Section: Preservative Toxicitymentioning

confidence: 99%

Formulation Considerations for the Management of Dry Eye Disease

2021

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Dry eye disease (DED) is one of the most common ocular surface disorders characterised by a deficiency in quality and/or quantity of the tear fluid. Due to its multifactorial nature involving several inter-related underlying pathologies, it can rapidly accelerate to become a chronic refractory condition. Therefore, several therapeutic interventions are often simultaneously recommended to manage DED efficiently. Typically, artificial tear supplements are the first line of treatment, followed by topical application of medicated eyedrops. However, the bioavailability of topical eyedrops is generally low as the well-developed protective mechanisms of the eye ensure their rapid clearance from the precorneal space, thus limiting ocular penetration of the incorporated drug. Moreover, excipients commonly used in eyedrops can potentially exhibit ocular toxicity and further exacerbate the signs and symptoms of DED. Therefore, formulation development of topical eyedrops is rather challenging. This review highlights the challenges typically faced in eyedrop development, in particular, those intended for the management of DED. Firstly, various artificial tear supplements currently on the market, their mechanisms of action, as well as their application, are discussed. Furthermore, formulation strategies generally used to enhance ocular drug delivery, their advantages and limitations, as well as their application in commercially available DED eyedrops are described.

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Corneal toxicity studies in rabbits and dogs with hydroxyethyl cellulose and benzalkonium chloride

Cited by 20 publications

References 21 publications

A Comparison of the Effects of Benzalkonium Chloride on Ocular Surfaces between C57BL/6 and BALB/c Mice

A Comparison of the Effects of Benzalkonium Chloride on Ocular Surfaces between C57BL/6 and BALB/c Mice

Efficacy of two chondroitin sulfate ophthalmic solutions in the therapy of spontaneous chronic corneal epithelial defects and ulcerative keratitis associated with bullous keratopathy in dogs

Formulation Considerations for the Management of Dry Eye Disease

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