Percutaneous permeation modifiers: enhancement versus retardation

Among the factors determining the propensity of a chemical to induce skin allergy are the penetration into skin and the kinetics of ingress. Confocal Raman spectroscopy can provide such information as it enables direct, spatially resolved measurement of the skin and of any chemical uptake. Several chemicals can be monitored at once, and the method is non-destructive (light in, light out) so that the skin can be kept intact for repeated and continuous measurement. Raman spectroscopy was used to follow the penetration of 2.5 weight percent trans-cinnamaldehyde and its delivery vehicle into skin in vitro, up to 24 h after topical application. A custom-made Bronaugh-type diffusion cell that was suitable for the Raman experiment was used. Four different vehicles were tested: absolute ethanol, 50% aqueous ethanol, propylene glycol and acetone:olive oil (4:1); these gave different time scales for cinnamaldehyde penetration. The acetone:olive oil vehicle phase-separated on the skin surface and the cinnamaldehyde penetrated at different rates in the different phases, which may be of significance since this is the preferred solvent for the local lymph node assay (an in vivo animal test used to generate hazard information on skin sensitization). In conclusion, the Raman method gives valuable detailed information on chemical ingress, clearly differentiates between different delivery rates and allows solvent monitoring alongside the chemical of interest.

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“…4 , 6 ). Several reviews discuss the enhancing ability and mechanisms of the solvents used in this study [35][36][37] .…”

Section: Discussionmentioning

confidence: 99%

Measuring the Penetration of a Skin Sensitizer and Its Delivery Vehicles Simultaneously with Confocal Raman Spectroscopy

Bonnist

Gorce

MacKay

et al. 2011

Skin Pharmacol Physiol

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“…The temperature was maintained at 37±0.1°C. After incubation for 1 h at 37°C, the formulations were applied in an infinite dose approach (100 mg of each formulation, which corresponds to 750 μg of MTZ) evenly over a surface area of 1.77 cm 2 . The donor chamber was covered with Parafilm® to minimize evaporation of the formulations.…”

Section: In Vitro Skin Permeation Studiesmentioning

confidence: 99%

“…Each set of experiments was run in six replicates. At the end of each time interval (1,2,4,8,12,16,20, and 24 h), the skin surface was wiped with cotton ball soaked with 1× PBS. The tape-stripping method (average ten strips) was used to remove the SC layer (20).…”

Section: In Vitro Skin Permeation Studiesmentioning

confidence: 99%

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Effect of Hydrocarbon Chain Length in 1,2-Alkanediols on Percutaneous Absorption of Metronidazole: Toward Development of a General Vehicle for Controlled Release

Jia

Zhang

et al. 2014

AAPS PharmSciTech

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Abstract. The objective of the present study is to investigate the effect of hydrocarbon chain length in 1,2-alkanediols on percutaneous absorption of metronidazole (MTZ). Twelve formulations (1,2-propanediol, 1,2-butanediol, 1,2-pentanediol, 1,2-hexanediol in 4% concentration, 1,2-hexanediol, and 1,2-heptanediol in 1% concentration, in the absence and presence of 1,4-cyclohexanediol, respectively) were studied in an in vitro hairless mouse skin model using Franz diffusion cell. Based on the flux values and retardation ratios (RR), a penetration retardation effect on percutaneous absorption of MTZ was observed for the formulations containing 1,2-diols having six-to seven-carbon chain in the presence of 1,4-cyclohexanediol (1,2-hexanediol with chain length of six hydrocarbons, RRs are 0.69 and 0.76 in the concentration of 4% and 1%, respectively; 1,2-heptanediol with chain length of seven hydrocarbons, RR is 0.78 in the concentration of 1%). On the other hand, no retardation effect was observed in formulations containing short alkyl chains (RRs of 1,2-propanediol, 1,2-butanediol, and 1,2-pentanediol are 0.99, 1.61, and 0.96, respectively). Instead, a penetration enhancement effect was observed for 1,2-diols having four and five carbons. In other words, effect of 1,2-alkanediols on percutaneous absorption of MTZ can be systematically modulated by simply varying number of -CH 2 groups in the hydrocarbon chain-from being a penetration enhancer to retardant. These observations shed light on mechanism of the penetration enhancement and retardation effect and provide insight into rational design of penetration enhancers and retardants. Furthermore, the combination of 1,2-alkanediols and 1,4-cyclohexanediol could become a general vehicle for controlled release of pharmaceutical and cosmetic active ingredients.

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“…This mechanism of action was suggested to explain the effect of retarding the penetration of other chemicals observed for one structural analogue of Azone [ 162 ] and several oxazolidone derivatives [ 163 ] . Despite the broad potential applications of penetration retardants -ranging from localized targeting of therapeutic agents, sunscreen products, and insect repellents in the superfi cial SC layers to protection from systemic absorption of chemical warfare, toxic spills, and pesticides -not many studies have investigated possible mechanisms to retard the penetration through SC [164][165][166][167][168] .…”

Section: Strengthening the Sc Barriermentioning

confidence: 99%

Molecular Organization of the Lipid Matrix in Stratum Corneum and Its Relevance for the Protective Functions of Human Skin

Boncheva

2012

Treatment of Dry Skin Syndrome

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Percutaneous permeation modifiers: enhancement versus retardation

Cited by 47 publications

References 51 publications

Measuring the Penetration of a Skin Sensitizer and Its Delivery Vehicles Simultaneously with Confocal Raman Spectroscopy

Measuring the Penetration of a Skin Sensitizer and Its Delivery Vehicles Simultaneously with Confocal Raman Spectroscopy

Effect of Hydrocarbon Chain Length in 1,2-Alkanediols on Percutaneous Absorption of Metronidazole: Toward Development of a General Vehicle for Controlled Release

Molecular Organization of the Lipid Matrix in Stratum Corneum and Its Relevance for the Protective Functions of Human Skin

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