An approach for development of alternative test methods based on mechanisms of skin irritation

Osborne, Rosemarie; Perkins, Mary A.

doi:10.1016/0278-6915(94)90174-0

Cited by 104 publications

(53 citation statements)

References 7 publications

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“…A good correlation between in vitro cytotoxicity assays and in vivo skin irritation has been demonstrated for surfactants of different irritation potential, and since then, cytotoxicity assays became largely used to predict the irritation potential of substances (28). Although this method does not determine the exact concentration of a substance that may be toxic to the skin (since it does not mimic the complex structure of the skin), it allows comparing the cytotoxic potential of new formulations to that of compounds considered safe or irritant (26).…”

Section: Discussionmentioning

confidence: 99%

Microemulsions Containing Medium-Chain Glycerides as Transdermal Delivery Systems for Hydrophilic and Hydrophobic Drugs

et al. 2009

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Abstract. We evaluated the ability of microemulsions containing medium-chain glycerides as penetration enhancers to increase the transdermal delivery of lipophilic (progesterone) and hydrophilic (adenosine) model drugs as well as the effects of an increase in surfactant blend concentration on drug transdermal delivery. Microemulsions composed of polysorbate 80, medium-chain glycerides, and propylene glycol (1:1:1, w/w/w) as surfactant blend, myvacet oil as the oily phase, and water were developed. Two microemulsions containing different concentrations of surfactant blend but similar water/oil ratios were chosen; ME-lo contained a smaller concentration of surfactant than ME-hi (47:20:33 and 63:14:23 surfactant/oil/water, w/w/w). Although in vitro progesterone and adenosine release from ME-lo and MEhi was similar, their transdermal delivery was differently affected. ME-lo significantly increased the flux of progesterone and adenosine delivered across porcine ear skin (4-fold or higher, p<0.05) compared to progesterone solution in oil (0.05±0.01 μg/cm 2 /h) or adenosine in water (no drug was detected in the receptor phase). The transdermal flux of adenosine, but not of progesterone, was further increased (2-fold) by ME-hi, suggesting that increases in surfactant concentration represent an interesting strategy to enhance transdermal delivery of hydrophilic, but not of lipophilic, compounds. The relative safety of the microemulsions was assessed in cultured fibroblasts. The cytotoxicity of ME-lo and ME-hi was significantly smaller than sodium lauryl sulfate (considered moderate-to-severe irritant) at same concentrations (up to 50 μg/mL), but similar to propylene glycol (regarded as safe), suggesting the safety of these formulations.

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Section: Discussionmentioning

confidence: 99%

Microemulsions Containing Medium-Chain Glycerides as Transdermal Delivery Systems for Hydrophilic and Hydrophobic Drugs

et al. 2009

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“…A good correlation with in vivo human skin data has been demonstrated for surfactants of different chemical types and irritation potential (16). However, in spite of the advantages of in vitro models, cell culture lacks some of the properties of intact skin, such as its selective barrier role or the interaction between different cell types.…”

Section: Introductionmentioning

confidence: 98%

Assessment of the Potential Skin Irritation of Lysine-Derivative Anionic Surfactants Using Mouse Fibroblasts and Human Keratinocytes as An Alternative to Animal Testing

et al. 2004

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Purpose. The aim of this study was to identify new surfactants with low skin irritant properties for use in pharmaceutical and cosmetic formulations, employing cell culture as an alternative method to in vivo testing. In addition, we sought to establish whether potential cytotoxic properties were related to the size of the counterions bound to the surfactants.Methods. Cytotoxicity was assessed in the mouse fibroblast cell line 3T6, and the human keratinocyte cell line NCTC 2544, using the MTT assay and uptake of the vital dye neutral red 24 h after dosing (NRU).Results. Lysine-derivative surfactants showed higher IC 50 s than did commercial anionic irritant compounds such as sodium dodecyl sulphate, proving to be no more harmful than amphoteric betaines. The aggressiveness of the surfactants depended upon the size of their constituent counterions: surfactants associated with lighter counterions showed a proportionally higher aggressivity than those with heavier ones.Conclusions Synthetic lysine-derivative anionic surfactants are less irritant than commercial surfactants such as sodium dodecyl sulphate and Hexadecyltrimethylammonium bromide and are similar to Betaines. These surfactants may offer promising applications in pharmaceutical and cosmetic preparations, representing a potential alternative to commercial anionic surfactants as a result of their low irritancy potential.

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“…On the contrary, the overall hydrophobicities of the molecules become larger [12,39]. Hence, causing greater amounts of surfactant adsorbed on the HaCaT cell membrane, leading to cellular disintegration, eventually cell death and the concomitant release of keratinocyte cytoplasm containing the proinflammatory cytokine, IL-1α [40,41].…”

Section: Discussionmentioning

confidence: 99%

“…The HaCaT cell line was exposed to100 μL of different concentrations of acylglutamate surfactants and CPZ solutions (1,5,10,20,40, 80, 160 and 320 μg/mL, pH 7.2), followed by incubation for 24 h and cell viability was assessed by MTS assay.…”

Section: Surfactant Treatmentmentioning

confidence: 99%

In Vitro Cytotoxicity and Phototoxicity Assessment of Acylglutamate Surfactants Using a Human Keratinocyte Cell Line

2014

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In the current study, human keratinocyte cell line was used as in vitro cell culture model to elucidate the effects of the fatty acid chain length of acylglutamate (amino acid-based surfactant) namely, sodium cocoyl glutamate, sodium lauroyl glutamate, and sodium myristoyl glutamate on their cytotoxicity and the ultraviolet B induced phototoxicity. The endpoint used to assess toxicity was a tetrazolium-based assay whereas, the phototoxic potential of acylglutamate surfactants was predicted using two models namely, the Photo-Irritation Factor and Mean Photo Effect. The results of this study showed that the fatty acid chain length of acylglutamate greatly influences toxic effects on human keratinocyte cells. In addition, all the acylglutamate surfactants tested on human keratinocyte cells demonstrated significantly less cytotoxicity (when irradiated and non-irradiated with ultraviolet B light; p < 0.05) and no phototoxic potential was observed in any of the acylglutamate surfactants, when compared with the positive control chlorpromazine. In conclusion, the in vitro studies confirm the suitability of sodium lauroyl glutamate destined for the synthesis and stabilization of lipid nanoparticles.

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An approach for development of alternative test methods based on mechanisms of skin irritation

Cited by 104 publications

References 7 publications

Microemulsions Containing Medium-Chain Glycerides as Transdermal Delivery Systems for Hydrophilic and Hydrophobic Drugs

Microemulsions Containing Medium-Chain Glycerides as Transdermal Delivery Systems for Hydrophilic and Hydrophobic Drugs

Assessment of the Potential Skin Irritation of Lysine-Derivative Anionic Surfactants Using Mouse Fibroblasts and Human Keratinocytes as An Alternative to Animal Testing

In Vitro Cytotoxicity and Phototoxicity Assessment of Acylglutamate Surfactants Using a Human Keratinocyte Cell Line

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