Skin penetration of chemicals: quantitative in vivo ......Quantification of skin penetration of...

18 Sept 2019, OEESC, Dublin

Skin penetration of chemicals: quantitative in vivo analysis by Raman spectroscopy

PROTECTION AGAINST

MICROORGANISMS,

CHEMICALS,

ALLERGENS,

POLLUTANTS,…

Gerwin Puppels, Claudio Nico, Johanna de Sterke, Paul Pudney,* Peter Caspers*Unilever Research Port Sunlight, UK

Analysis of skin penetration / permeation

Outline

Raman spectroscopy & in vivo skin analysis

Non-invasive analysis of the penetration of topically applied materials

Quantification Concentration (mg/cm3)

Total uptake (mg/cm2)

Flux (mg/cm2.h)

Example: retinol

Applications

molecular composition of the skin - spatially resolved

living

epidermis

penetration

of topically

applied

materials

UV, season

age, body site, response to challenges, ….

O C O O C O

500 1000 1500 2000

lactate

glycogen

Fatty acid

cholesterol

elastin

collagen

Proteins

Sugars

Lipids

Interpretation of spectra

Raman spectrum of stratum corneum

Signal contributions of:

Proteins

amino acids

sweat constituents

lipids

in vivo skin

400 600 800 1000 1200 1400 1600 1800

Raman shift, cm-1

fit-result

residual

window

dermis

epidermis

500 1000 1500

distance to skin

surface

skin surface

0 20 40 60 80 100 120 140 160 180 2000

depth (micron)

skin characterization

• skin typing

• age related effects

• seasonal effects

• skin conditions

• skin lesions

Topically applied products

penetration & permeation of:•drugs

•personal care actives •perfumes (fragrances)

•chemicals

0 10 20 30

productconcentration

Distance to skin surface (μm)

product

Skin penetration of chemicals: quantitative in vivo analysis

in vivo skin

400 600 800 1000 1200 1400 1600 1800

Raman shift, cm-1

fit-result

residual

400 600 800 1000 1200 1400 1600 1800

Raman shift, cm-1

fit-result

residual

SC EDproduct

RA ~ ρA

~ Ilaser

~ f(Ω,V)

• RA: intensity of the Raman signal of a compound A [photons/s]

• gA: concentration of compound A in the measurement volume V [kg/m3]

• Ilaser: laser light intensity [J/s]

• V: measurement volume [m3]

• Ω: measurement configuration

• kA: proportionality constant (property of compound A)

RA = kA . Ilaser . f(Ω,V) . gA

= CA(Ilaser,Ω,V) . ρA

homogeneous medium: compound A in solution

Skin: an inhomogeneous medium

The skin is an inhomogeneous medium

Quantification of skin penetration of products

The skin is an inhomogeneous medium

RB= CA/B .

gA = RA

CA/B. gB

• gprotein,skin(z)

the protein concentration in the skin can be estimated from water concentration profiles in the skin

Eliminating unknowns

z 0 20 40 60 80 100 120 140 160 180 2000

Distance z to skin surface (µm)

sc epidermis dermis

• mass-fractionwater,skin = 0.25 - 0.65 (SC)

• mass-fractionwater,skin = 0.65 - 0.70 (epidermis)

• mass-fractionwater,skin = 0.70 – 0.75 (dermis)

z 0 20 40 60 80 100 120 140 160 180 2000

Distance z to skin surface (µm)

sc epidermis dermis

density dry SC = 1.15 g/cm3

60% protein;

15% lipids;

20 - 30% natural moisturizing factor

• ρA(z) = RA(z)

Rprotein(z).

1CA/protein

. ρprotein,skin(z)

1.RA(z)

Rprotein(z): from skin Raman spectra

2. CA/protein : from calibration experiments

3. ρprotein,skin(z) : from water concentration profiles

Proportionality constants Cmaterial:solvent

Cmaterial:solvent = (Rmaterial / Rsolvent) / (mmaterial / msolvent)

Cretinol:protein = Cretinol:ethanol . Cethanol:water / Cprotein:water

• 0.3% retinol in 70% ethanol – 30% PG

• Volar forearm

• 70 ml on skin area of 4 x 4 cm2

• 10 min

distance to skin surface (mm)

0 5 10 15 20 250

time (h)

1 2 3 4 5 6

Flux: 0.6 mg/cm2.h

distance to skin surface (mm)

0 5 10 15 20 25

time (h)

1 2 3 4 5 6

Flux: 8 mg/cm2.h

• retinol

• max. retinol concentration in SC ≃ retinol concentration in formulation after evaporation of ethanol

• 40% of applied dose detected in the skin

• After 6 hrs: 75% skin

• propylene glycol

• 16% of applied dose detected in the skin

• After 6 hrs: 20% skin

Skin penetration of topically applied materials

• In vivo Raman spectroscopy can provide• Qualitative information

• Did a material penetrate into the skin?

• How far into the skin?

• How fast?

• How long does it stay in the skin?

• Semi-quantitative information

• Comparison of efficiency of delivery of an active for different formulations.

• Comparison of delivery for different application times

• …

• Quantitative information

• How much penetrated into the skin (µg.cm-2)?

• What is the flux into the skin (µg/s-1.cm-2)?

Skin penetration of chemicals: quantitative in vivo ......Quantification of skin penetration of...

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