P Xiao 1,2, H Singh 1, X Ou 1, A R Caparnagiu 3, LI Ciortea 2, EP Berg 2 and RE Imhof 1,2
1 Photophysics Research Centre, London South Bank University, London SE1 0AA, UK
2 Biox Systems Ltd, Technopark House, 90 London Road, London SE1 6LN, UK3
3 Kingston University, 53–57 High Street, Surrey KT1 1LQ, UK
Introduction
Capacitance based sensors, has shown potentials in skin hydration imaging, surface analysis, 3D surface profiles, and skin micro relief measurements[1-4]. Our latest studies showed that apart from water, capacitance sensors are also sensitive to many solvents, due to their high dielectric constants, which makes it very useful for in-vivo trans-dermal drug delivery studies. In this paper, we present our latest in-vivo trans-dermal drug delivery study by using capacitance sensors, AquaFlux and OTTER. The results shows that capacitance sensors can be a useful tool for studying in-vivo solvent penetration through skin, as it gives an dynamic 2D images of solvent penetrating through skin, and combining with tape stripping, it is also possible to get solvent depth profiles within skin.
Apparatus
Figure 1 shows the photos and schematic diagrams of opto-thermal transient emission radiometry (OTTER), capacitance sensor (Fujitsu), and AquaFlux (Biox Systems Ltd). OTTER is an infrared remote sensing technology which uses a pulse laser as heat source and fast infrared detector to detect the consequent black-body radiation increase, the shape of the signal depends on the optical properties, thermal properties and layered structure of the skin sample. capacitance sensor used has 256x300 pixels with 50mm spatial resolution and 8-bit gray-scale value resolution per pixel. AquaFlux is novel close-chamber TEWL method, the cylindrical measurement chamber is open at one end which is in contact of skin surface, and it closed at another end with a cold plate - condenser. The closed chamber with a condenser helps to stabilize the measurement environment and therefore enhance repeatability and accuracy of the measurement results.
Results and Discussions
In this study, three solvents are chosen for study, DMSO, Glycerol, and Ethylene Glycol, due to their high dielectric constants, see Table 1. In each measurement, a small amount of solvent is applied to the volar forearm for a few minutes. After the skin surface is wiped dry, tape stripping is performed. capacitance sensor measurements are performed both before and after the solvent applications, and after each strip.
Table 1 Dielectric Constants of the solvents and skin
Figure 2 and 3 are the results for DMSO, Glycerol and Ethylene Glycol. The capacitance skin images can clearly discriminate between the solvents and normal skin due to dielectric constant differences. The results show that DMSO penetrates more and deeper than Glycerol, as DMSO residue is still visible after 10 strips, whilst Glycerol residue disappears after 5 strips.
By measuring the grayscale values of pure solvents, pure skin itself, we can work out the solvent absolute concentration [%,volume in volume] using following equation.
Where Gmix is the grayscale value of skin after solvent application, Gskin is the grayscale value of skin itself, and Gsolvent is the grayscale value of pure solvent. C is the solvent absolute concentration in skin in volume percentage. Figure 4 shows the absolute concentration [%, vol/vol] of the DMSO, Glycerol, and Ethylene Glycol on skin before application, after, and subsequently during tape stripping. The results show that DMSO can penetrate most into skin, and still present after 10 tape stripping, whilst Glycerol and Ethylene Glycol are disappeared after about 5 or 6 tape stripping.

OTTER is an infrared remote sensing technology that has been used for trans-dermal drug delivery studies [5]. Figure 5 shows the comparison of the capacitance sensor skin image grayscale values and OTTER data for Glycerol aplication. The results show a good correlation between capacitance sensor data and OTTER data. The TEWL results measured by AquaFlux [6] also increased as tape stripping number increased, work is in progress to correlation the capacitance sensor grayscale results with TEWL results.

By using the thickness information of each tape strip, we can also re-construct the Fig 2 and 3 images into 3D solvent depth profiles, see Fig 6.
Conclusions
The study shows that capacitance sensor imaging is a powerful tool for solvent penetration through stratum corneum. The
capacitance sensors are not only sensitive to water, but also sensitive to solvents with relative large dielectric constants. The capacitance sensor results correlates well with well established OTTER technology results. Combining with tape stripping, we can also re-construct the 3D solvent depth profiles within stratum corneum. The next step is to perform additional correlation tests between the capacitance sensor grayscale results with AquaFlux TEWL results.
Acknowledgement
We thank EPSRC and London South Bank University for the financial support.
References
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Stratum Corneum V conference, July 11-13, 2007, Cardiff, UK.
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