397 The Human Stratum Corneum
on vitro-skin, and showed that viscosity is the main factor in determining the spreading
rate of emollients, followed by surface tension and density.69
Berkey et al. have recently investigated the structure-function relationship governing the
performance of a range of 14 emollients by measuring drying stress on ex vivo skin after
application of the emollient.95 Their results show that the ability of the emollient to reduce
skin drying stress is dependent upon its ability to penetrate the SC and replace water, which
in turn is dependent on the molecular weight, diffusivity, and viscosity of the emollient. A
list of emollients used in the study and the correlation between drying stress reduction and
the volume of penetration of the emollient are shown in Figures 10 and 11, respectively.95
This study provides a rational basis for selecting emollients. Additional factors such as skin
feel and spreadability will also be factors in the choice of emollients. In separate studies
using the same methodology, Levi et al. have shown that glycerin and petrolatum also
reduce drying stress.97 In contrast, treatment with a harsh surfactant such as SDS has been
shown to increase the drying stress.97
LIPIDS
Bilayer lipids such as fatty acids, ceramides and sterol are reduced in skin under compromised
conditions such as dry skin,98 aging skin,99 and atopic skin.100 The hypothesis is that while
the traditional moisturizers with humectants, emollients, and occlusives can reduce the
water loss, the use of lipids may provide enhanced benefits by restoring the natural barrier
through replenishing the lost lipids. Use of these lipids and the mechanisms by which they
may restore the barrier is briefly reviewed below.
Lipids in skincare can be broadly classified into physiological lipids such as ceramides, fatty
acids, and cholesterol, as well as nonphysiological lipids such as vegetable oils and a wide
variety of synthetic and natural lipids.
Figure 11. Emollient penetration volume into SC in in-vitro tests vs peak drying stress reduction after
treatment with the emollient. Figures reproduced with permission from Berkey et al.95

398 JOURNAL OF COSMETIC SCIENCE
Under dry skin conditions when the TEWL is high, skin begins to build its SC barrier at a
higher-than-normal rate, and this results in an abnormal barrier.2,3 Nonphysiological lipids
such as vegetable oils, mineral oils, and petrolatum may help reduce the TEWL by forming
an occlusive layer and allowing skin to build the barrier at a normal rate. Physiological
lipids, on the other hand, may help strengthen the barrier by intercalating into the lipid
layer and reinforcing the barrier.
Fatty acids and triglycerides have been in skincare formulations for decades.66 Triglycerides
used as carriers for lipids such as fatty acids themselves can undergo hydrolysis by skin
enzymes or bacteria producing fatty acids that are beneficial to the skin.65,66 Lately,
combinations of fatty acids, sterols, and ceramides are seeing increased use in moisturizing
formulations with skin identical lipid claims.54 They can be formulated at specific ratios
into one or more bilayer lipid structures in a vesicular form that can transferred to skin
to provide a moisture barrier. The synthetic ceramides currently available include shorter
chain versions of ceramide 3 (Ceramide NP) and ceramide 6 (Ceramide AP). For cost
reasons and complexities involved in the synthesis of skin identical ceramides, they are not
normally found in current formulations.
There are clinical studies showing the benefits of incorporating ceramides and fatty acids
in restoring the skin barrier.54,101 Bilayers formed by these lipids can indeed strengthen the
barrier in a way similar to occlusive moisturizers that form a layer on the SC. There have
also been suggestions that these lipids intercalate into the compromised SC bilayer and
restore the barrier.
Another hypothesis is that fatty acids and ceramides from externally applied formulations
are taken by the skin to build better lipids. The latter argument is supported by in vitro
skin equivalent cell culture studies with fatty acids101,102 and ceramides.103 For example,
Bouwstra and team have shown that fatty acids such as palmitic acid can be taken up by skin
and elongated into longer chain fatty acids that become part of the SC barrier.102 Similarly,
technical data presented by the Evonik research group using living skin equivalent models
show that short chain synthetic ceramides applied from topical systems can be taken up
by skin to become part of the skin bilayer lipids.104 In the case of fatty acids, Yarova et al.
used deuterated fatty acids that have further shown that in in vivo studies, palmitic acid
is elongated to C24 and C28 fatty acids.105 This type of in vivo study is a confirmation of
such lipid utilization by skin to rebuild its barrier. Such studies have not been conducted
with ceramides so far. In fact, the penetration of ceramides in healthy skin itself requires
further confirmation. Ceramides, being a two tailed highly hydrophobic lipid, will require
appropriate solvents and penetration enhancers to ensure its penetration into deeper layers.
While some of the spectral imaging studies using ATR/IR techniques have reported that
the ceramides do not penetrate deeper layers and stays in the crevices and cracks in skin,106
other studies using specific forms, such as microemulsion forms, have claimed that the
ceramide penetrates deeper layers.107 Further studies are needed to understand the level of
penetration of ceramides into the skin and its incorporation in the bilayers and utilization
by skin.
BIO-ACTIVE COSMETIC INGREDIENTS
In addition to moisturizers, there are several actives that are included in personal care
formulations for advanced skincare benefits. These include antiaging and skin pigmentation