387 The Human Stratum Corneum
of surfactants, with anionic surfactants showing higher irritation tendency compared to
amphoteric and nonionic surfactants. This is consistent with the pragmatic approach
that formulators have been using over the years to increase mildness towards skin by
increasing the size of the polar head group. For example, it is well known that harshness
of ethoxylated sulfates follow the order: SLS SLES 1EO SLES 2 EO SLES 3EO.
This can be generalized further with more quantitative relationships, relating headgroup
structural parameters to protein denaturation tendency.
The molecular mechanism involved in denaturation of proteins by surfactants in aqueous
solutions is thought to be due to the binding of surfactants to the proteins resulting in
the formation of micelle-like structures on the protein backbone and causing significant
electrostatic repulsion within the network.34 This in turn unravels the tertiary structure
of proteins. This charging of the structure in the case of insoluble proteins such as zein
results in dissolution of the protein. In contrast, in the case of crosslinked proteins such
as keratin, this results in osmotic driven swelling of proteins. Based on this hypothesis,
Lips et al. examined a correlation between micelle charge density and the dissolution of
zein using a variety of surfactants and found a linear correlation between micelle charge
density and the protein dissolution.34 Micelle zeta potential also correlated linearly with
the protein dissolution. Since the zeta potential of micelles is related to its charge density,
both the parameters correlating with the dissolution are not surprising, and overall, these
correlations support the hypothesis that micelle charge density is a predictive measure of
the denaturing potential, and hence the irritation tendency of the surfactants.
The role of micelle charge density as a key predictive parameter is further evident from the
work of Morris et al., which showed that the penetration of anionic surfactants into human
skin as measured from Franz diffusion experiments correlated linearly with the micelle
Figure 6. The correlation between cytokine release in-vitro and clinical TEWL measurement in a patch test.
Data from Walters et al. TEWL measurements are from in-vivo patch testing.45

388 JOURNAL OF COSMETIC SCIENCE
charge density measured from dynamic light scattering measurements.46 Morris et al. also
showed that the micelle size did not correlate with the penetration into the skin, suggesting
that size is not the main factor, but rather that charge density is the primary factor driving
the penetration of charged surfactants into skin. Figure 7 shows the correlation of surfactant
micelle charge density with skin penetration and protein denaturation.
One last point to be addressed regarding penetration of anionic surfactants into skin is
whether micelles penetrate through intact SC. The observation that micelle charge density
correlates with penetration of surfactants into skin does not imply that micelles penetrate
through healthy SC. In fact, Morris et al. have shown that the penetration remains essentially
plateaued above CMC, indicating that micelles do not penetrate through SC.47 If the skin
is exposed to surfactant solutions for a longer period such as several hours, it can damage
the SC, possibly resulting in penetration of the micelles.47 The reason micelle charge density
correlates with penetration is because the surfactant aggregates forming on the protein
backbone are similar to that of micelles, and have similar charge densities as the micelles.
The focus of discussion so far has centered around surfactant interactions with proteins
which correlate with the skin irritation tendencies of surfactants. This may be because the
rapid penetration of surfactants may be through hydrophilic pathways linked to protein
channels rather than the slower lipid pathway. Progressive alterations of the lipid matrix by
harsh surfactants also can contribute to SC damage, which may impact the desquamation
process, resulting in the formation of dry and flaky skin. In this context, the interaction of
surfactants with the lipid matrix is examined below.
SURFACTANT INTERACTIONS WITH SC LIPIDS
Surfactants are designed to remove oily lipids, specifically sebaceous lipids, during cleansing.
However, the cleansing system does not know the difference between sebaceous lipids and
the integral bilayer lipids that imparts SC its barrier properties. Surfactants can damage
Figure 7. Surfactant penetration into human cadaver skin in vitro from a variety of anionic-based surfactant
solutions versus zeta potential of the surfactant solutions (graph on the left) (b) Zein solubility in surfactant
solutions versus (absolute) zeta potential of the surfactant solutions (graph on the right). Figure reproduced
from Morris et al.47 Micelle zeta potential correlates with both surfactant penetration into skin and protein
denaturation.