Determination of eye irritation potential of low-irritant products: comparison of in vitro results with the in vivo draize rabbit test

Nóbrega, Andréa Martins da; Alves, Eloisa Nunes; Presgrave, Rosaura de Farias; Costa, Rodrigo Netto; Delgado, Isabella Fernandes

doi:10.1590/s1516-89132012000300008

Cited by 14 publications

(8 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Results from HET‐CAM irritation tests were in agreement with in vitro observations, confirming not only the sensitivity of the in vitro test but also the nonirritant properties of the developed formulation and suitability for ocular administration . These results are in accordance with those obtained by other groups working with PLGA‐NPs for ocular applications . We anticipate that encapsulation of memantine within the NP aqueous interior acts to slow memantine release and therefore reduces cell exposure to potentially cytotoxic concentrations of this agent.…”

Section: Discussionsupporting

confidence: 88%

“…The application of 0.3 mL of free memantine onto the chorioallantoic membrane, induced small hemorrhages (Figure B) suggestive of mild irritation. In contrast instillation of the same volume and concentration of MEM‐NPs was found to be well‐tolerated and induced no detectable irritation (Figure C,D) . Upon completion of these in vitro tests, a tolerance assay was conducted in male albino rabbits.…”

Section: Resultsmentioning

confidence: 98%

“…Subsequent in vivo ocular tolerance assays were performed using primary eye irritation test of Draize et. al (1994) with New Zealand rabbits (male, 2.5 kg) ( n = 3/group) . The formulation was instilled in the conjunctival sac of the right eye and a gentle massage was applied.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Memantine‐Loaded PEGylated Biodegradable Nanoparticles for the Treatment of Glaucoma

Sánchez-López

Egea

Davis³

et al. 2017

Small

View full text Add to dashboard Cite

Glaucoma is a multifactorial neurodegenerative disease associated with retinal ganglion cells (RGC) loss. Increasing reports of similarities in glaucoma and other neurodegenerative conditions have led to speculation that therapies for brain neurodegenerative disorders may also have potential as glaucoma therapies. Memantine is an N-methyl-d-aspartate (NMDA) antagonist approved for Alzheimer's disease treatment. Glutamate-induced excitotoxicity is implicated in glaucoma and NMDA receptor antagonism is advocated as a potential strategy for RGC preservation. This study describes the development of a topical formulation of memantine-loaded PLGA-PEG nanoparticles (MEM-NP) and investigates the efficacy of this formulation using a well-established glaucoma model. MEM-NPs <200 nm in diameter and incorporating 4 mg mL of memantine were prepared with 0.35 mg mL localized to the aqueous interior. In vitro assessment indicated sustained release from MEM-NPs and ex vivo ocular permeation studies demonstrated enhanced delivery. MEM-NPs were additionally found to be well tolerated in vitro (human retinoblastoma cells) and in vivo (Draize test). Finally, when applied topically in a rodent model of ocular hypertension for three weeks, MEM-NP eye drops were found to significantly (p < 0.0001) reduce RGC loss. These results suggest that topical MEM-NP is safe, well tolerated, and, most promisingly, neuroprotective in an experimental glaucoma model.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Resultsmentioning

confidence: 98%

See 1 more Smart Citation

Memantine‐Loaded PEGylated Biodegradable Nanoparticles for the Treatment of Glaucoma

Sánchez-López

Egea

Davis³

et al. 2017

Small

View full text Add to dashboard Cite

show abstract

“…Top-down approaches are for the identification of severe irritants, bottom-up approaches are for the identification of non-irritating substances (Barile, 2010;Engelke et al, 2013). This results in two testing strategies to replace one in vivo test and as of yet, neither strategy can be used to distinguish between non-irritants and mild irritants and this remains an on-going challenge (Barile, 2010;Nóbrega et al, 2012;Scott et al, 2010). The commercial aims of in vitro testing are to be faster and cheaper, although currently, the costs are roughly on par with Draize testing.…”

Section: Future Of In Vitro Alternativesmentioning

confidence: 99%

“…For developing or newly industrialized countries, Brazil, Russia, India, China and South Africa, the underlying challenge is getting them to understand the roles of in vitro tests, which is a continuing educational challenge. In order to overcome these issues, a re-evaluation of currently used in vitro tests may be required (Nóbrega et al, 2012).…”

Section: Future Of In Vitro Alternativesmentioning

confidence: 99%

An overview of current techniques for ocular toxicity testing

2015

View full text Add to dashboard Cite

Given the hazardous nature of many materials and substances, ocular toxicity testing is required to evaluate the dangers associated with these substances after their exposure to the eye. Historically, animal tests such as the Draize test were exclusively used to determine the level of ocular toxicity by applying a test substance to a live rabbit's eye and evaluating the biological response. In recent years, legislation in many developed countries has been introduced to try to reduce animal testing and promote alternative techniques. These techniques include ex vivo tests on deceased animal tissue, computational models that use algorithms to apply existing data to new chemicals and in vitro assays based on two dimensional (2D) and three dimensional (3D) cell culture models. Here we provide a comprehensive overview of the latest advances in ocular toxicity testing techniques, and discuss the regulatory framework used to evaluate their suitability.

show abstract

An overview of current alternative models in the context of ocular surface toxicity

Bonneau

Baudouin

Goazigo

et al. 2021

J of Applied Toxicology

View full text Add to dashboard Cite

The 21st century has seen a steadily increasing social awareness of animal suffering, with increased attention to ethical considerations. Developing new integrated approaches to testing and assessment (IATA) strategies is an Organisation for Economic Co‐operation and Development (OECD) goal to reduce animal testing. Currently, there is a lack of alternative models to test for ocular surface toxicity (aside from irritation) in lieu of the Draize eye irritation test (OECD guideline No. 405) performed in rabbits. Five alternative in vitro or ex vivo methods have been validated to replace this reference test, but only in combination. However, pathologies like Toxicity‐Induced Dry Eye (TIDE), cataract, glaucoma, and neuropathic pain can occur after exposure to a pharmaceutical product or chemical and therefore need to be anticipated. To do so, new models of lacrimal glands, lens, and neurons innervating epithelia are required. These models must take into account real‐life exposure (dose, time, and tear film clearance). The scientific community is working hard to develop new, robust, alternative, in silico, and in vitro models, while attempting to balance ethics and availability of biological materials. This review provides a broad overview of the validated methods for analyzing ocular irritation and those still used by some industries, as well as promising models that need to be optimized according to the OECD. Finally, we give an overview of recently developed innovative models, which could become new tools in the evaluation of ocular surface toxicity within the scope of IATAs.

show abstract

Determination of eye irritation potential of low-irritant products: comparison of in vitro results with the in vivo draize rabbit test

Cited by 14 publications

References 28 publications

Memantine‐Loaded PEGylated Biodegradable Nanoparticles for the Treatment of Glaucoma

Memantine‐Loaded PEGylated Biodegradable Nanoparticles for the Treatment of Glaucoma

An overview of current techniques for ocular toxicity testing

An overview of current alternative models in the context of ocular surface toxicity

Contact Info

Product

Resources

About