Clinics in Dermatology (2012) 30, 345–348
New treatments for restoring impaired epidermal barrier
permeability: Skin barrier repair creams
Zoe Diana Draelos, MD ⁎
Department of Dermatology, Duke University School of Medicine, 2444 North Main Street, High Point, NC 27262, USA
Abstract Skin health depends on an intact barrier composed of protein-rich corneocytes surrounded by
the lamellar intercellular lipids. This barrier provides waterproof protection for the body, preventing
infection, regulating electrolyte balance, maintaining body temperature, and providing a mechanism for
sensation. Damage to the skin barrier results in skin disease that can be treated by a variety of externally
applied substances, such as ceramides, hyaluronic acid, licorice extracts, dimethicone, petrolatum, and
paraffin wax. These substances are found in moisturizers that are sold as cosmetics and in prescriptions
as 510(k) devices. This contribution examines the formulation and effect of skin barrier creams.
© 2012 Elsevier Inc. All rights reserved.
Introduction viable epidermis, the nucleated cells possess tight, gap, and
adherens junctions with desmosomes and cytoskeletal
The skin barrier is an essential element of health, elements that contribute to the barrier. Barrier repair devices
separating the body from the external world. Without this attempt to mimic the intercellular lipids that are synthesized
barrier, human life could not exist. Protection is necessary in the keratinocytes during epidermal differentiation and then
from infectious organisms that might enter the body causing extruded into the extracellular domains. These lipids are
serious disease and possibly death. A means of regulating composed of ceramides, free fatty acids, and cholesterol,
electrolyte balance, body temperature, and sensation is also which covalently bind to the cornified envelope proteins.
part of this barrier. Although the barrier is self-maintaining, Changes in these intercellular lipids and alterations in
with replacement on a 14-day cycle, disease states may epidermal differentiation lead to barrier defects and,
perturb the barrier and delay repair or alter repair kinetics. To ultimately, skin disease.
meet this need, a variety of barrier repair products have been
introduced to speed the healing of barrier-impaired skin and
to maintain a healthy barrier. This article examines the Barrier products
construction and effect of these new barrier repair devices on
skin health. A variety of barrier repair products have been launched
into the prescription marketplace. These creams are different
The barrier than traditional over-the-counter (OTC) nonprescription
moisturizers because the U.S. Food and Drug Administration
(FDA) has approved them as a 510(k) device. The 510(k)
The skin barrier is formed by the protein rich cells of the
device approval process was originally developed to ensure
stratum corneum with intervening intercellular lipids. In the
the safety of equipment with an on/off switch. Lasers, light
⁎ Corresponding author. 2444 N Main St, High Point, NC 27262. devices, cardiac pacemakers, and insulin pumps represent
Tel.: +1 336 841 2040; fax: +1 336 841 2044. equipment requiring this type of approval. Although creams
E-mail address: [email protected]. are not traditionally thought of as “devices,” they received
0738-081X/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
doi:10.1016/j.clindermatol.2011.08.018
346 Z.D. Draelos
(501(k) approval because they induce a physical change in injection into the skin as a filler (Juvaderm Ultra and
the skin. This physical change was documented as an Juvaderm Ultra Plus, Allergan, Irvine, CA; Restylane and
increase in skin hydration resulting from a decrease in Perlane, Medicis Pharmaceutical Corp, Scottsdale, AZ) and
transepidermal water loss (TEWL). as a barrier repair product (Atopiclair, Graceway Pharma-
TEWL can be measured by an evaporimeter using two ceuticals, Bristol, TN; Hylatopic, Onset Therapeutics,
humidity meters. The humidity meters are encased in a probe Cumberland, RI). As a component of the extracellular
with a circular orifice that is placed on the skin surface. The matrix, hyaluronic acid is believed to stimulate neutrophil
distance between the humidity meters and the distance the migration, fibroblast proliferation, and neoangiogenesis.
humidity meters are from the skin surface is defined. The Research that evaluated the effect of a hyaluronic acid
amount of water vapor passing between the humidity meters sodium salt in the healing of episiotomy and cesarean section
over a given area is measured, and a computer calculates the surgical wounds 5 demonstrated a lower incidence of edema
grams of water lost per centimeter squared. and decreased wound exudate in the group treated with
Barrier repair products place a water-impervious film over hyaluronic acid sodium salt.
the skin surface that decreases TEWL. TEWL is elevated Two barrier products use hyaluronic acid as the main
when the skin barrier is damaged, representing the ingredient to enhance water holding (Bionect, JSJ Pharma-
physiologic signal for barrier repair initiated by ceramide ceuticals, Charleston, SC; Hylatopic, Onset Therapeutics).
synthesis. By decreasing TEWL, barrier creams hydrate the One contains 0.2% hyaluronic acid sodium salt, which
skin and create an environment optimal for healing. A variety functions as a humectant, in combination with other
of different formulations that produce barrier repair by humectants, such as glycerol and a 70% sorbitol solution
different mechanisms presently have 510(k) approval. These (Bionect, JSJ Pharmaceuticals).
510(k)-approved barrier creams are reviewed next based on In addition to humectants, occlusive ingredients are
their unique active ingredient. required to keep the water attracted by the humectant from
evaporating into the environment. These are oily substances,
Ceramide such as an emulsifying wax, that physically block TEWL.
Most good moisturizers use ingredients with occlusive and
humectant properties to increase skin hydration. The same
Ceramide synthesis is the first step in healing a damaged
hyaluronic acid sodium salt is combined in a foam
skin barrier. Nine different ceramides have been identified
formulation with glycerin as an added humectant, accompa-
and many synthetically duplicated for inclusion in moistur-
nied by dimethicone and petrolatum as occlusives (Hyla-
izer formulations. 1 The ceramides are distinguished by their
topic, Onset Therapeutics, Cumberland, RI).
polar head group architecture and by their hydrocarbon chain
properties. 2 A ceramide-dominant, triple-lipid barrier repair
formulation (EpiCeram, Promius Pharma, Bridgewater, NJ) Palmitoyl ethanolamide
was designed to correct the lipid-biochemical abnormalities
in atopic dermatitis. It contains capric acid, cholesterol, and A different approach to barrier repair is found in a 510(k)-
conjugated linolenic acid. In addition, candelilla and approved cream that contains a variety of moisturizers, such
petrolatum are included to decrease TEWL. EpiCeram as olive oil, glycerin, and vegetable oil, in addition to
received FDA approval in April 2006 for use as a palmitamide monoethanolamine (PEA; Mimyx, Stiefel,
nonsteriodal lipid barrier emulsion to manage the symptoms Research Triangle Park, NC). PEA is a fatty acid that is
of dry skin associated with a variety of dermatologic purported to be deficient in atopic skin. 6 It has been shown to
diseases. 3 It was compared with fluticasone cream in 121 decrease itch, perhaps because PEA may modulate the
patients with moderate to severe atopic dermatitis for 28 cannabinoid itch receptors in the skin. 7 In an open-label
days. EpiCeram reduced Scoring Atopic Dermatitis study of 2456 patients, the intensity of erythema, pruritus,
(SCORAD) scores, decreased pruritus, and improved sleep excoriation, scaling, lichenification, and dryness were
habits; however, faster improvement was seen with the significantly reduced, with a combined score reduction of
topical corticosteroid at day 14. 4 The unique aspect of this 58.6%. 8 There was no placebo in this noncontrolled
cream is that the ratio of the triple-lipid combination mimics prospective cohort study.
that of physiologic lipids.
Licorice extract
Hyaluronic acid
Other 510(k) device barrier creams contain a variety of
Another endogenous component of the skin necessary for botanical extracts. One currently marketed product contains
the maintenance of hydration is hyaluronic acid, a glycos- glycyrrhetinic acid and Vitis vinifera extracts (Atopiclair,
aminoglycan found in the dermis. Hyaluronic acid acts as a Graceway Pharmaceuticals) along with allantoin, α-bisabo-
sponge in the skin to attract and hold water, a function known lol, hyaluronic acid, and shea butter. Glycyrrhetinic acid is a
as humectancy. Hyaluronic acid is approved as a device for licorice extract that was reported to be safe by the Cosmetic
Skin barrier repair creams 347
Ingredient Review. It is able to block gap junction discharges. The silicone used in topical preparations is an
intracellular communication, but is cytotoxic at high odorless, colorless, nontoxic liquid. Because silicone is
concentrations. Glycyrrhetinic acid is mainly used in immiscible and insoluble in water, it is used in barrier
moisturizer formulations as an anti-inflammatory. 9 In an products with water-resistant capabilities. To date there is no
open-label multicenter study, the product reduced the median report of toxicity from the use of topical silicone. 15
visual analog scale rating for itching in atopic dermatitis Dimethicone is the first ingredient in a foam formulated
from 48.5 to 34.1 mm after 3 weeks of treatment, with a for the relief of irritation from dermatoses, such as atopic
further reduction to 24.6 mm after 6 weeks of treatment. 10 In dermatitis and allergic contact dermatitis (Neosalus, Quin-
a second study of 142 pediatric patients ages 6 months to 12 nova Pharmaceuticals, Newtown, PA). A combination of
years, the same formulation was compared with a vehicle cyclomethicone, a cyclic higher-viscosity silicone, and
cream and was statistically more effective in reducing the dimethicone are used in barrier creams designed to prevent
symptoms of mild to moderate atopic dermatitis. 11 It was skin sensitization to allergens (Tetrix, Coria Laboratories,
also effective for symptomatic relief of contact dermatitis. 12 Aliso Viejo, CA). 16 The water-in-oil emulsion is also
In addition to the anti-inflammatory effect of glycyr- resistant to water removal. 17
rhetinic acid, the Vitis vinifera extract, derived from grapes,
and α-bisabolol, derived from camomile, also serve as Paraffin wax
antioxidant, anti-inflammatory ingredients. Finally, allanto-
in, a heterocyclic organic compound, is a time-tested anti- Another time-tested occlusive agent to decrease TEWL is
inflammatory, as assessed by the Cosmetic Ingredient paraffin wax. Liquid paraffin combined with paraffin wax is
Review. 13 The combination of various botanical anti- the basis for another barrier cream designed to be used in the
inflammatories may be an alternative to more traditional management of superficial wounds, dermal ulcers, donor sites,
topical corticosteroids used for the treatment of dermatoses. burns, and radiation dermatitis (Biafine, OrthoNeutrogena,
Los Angeles, CA). The wax provides an artificial barrier until
Petrolatum healing can occur. The formulation was chemotactic for
macrophages and increased the interleukin-1/inteleukin-6
The oldest barrier product and the very first therapeutic ratio in epidermal wounds in healthy human volunteers. 18
moisturizer ever developed was petrolatum. Petrolatum is a Healing effects were also noted: the wax-based formulation
semisolid mixture of hydrocarbons obtained through the improving healing after the treatment of actinic keratoses. 19
dewaxing of heavy mineral oils. Pure cosmetic-grade
petrolatum is practically odorless and tasteless; however, OTC moisturizers vs 510(k)-approved barrier devices
hydrocarbon contaminants in lower-quality petrolatum may
account for the distinct chemical smell noted with some The use of occlusive, humectant, and anti-inflammatory
products. Petrolatum first appeared in the U.S. Pharmacopeia ingredients in 510(k) barrier devices may provide an
in 1880 and has been a widely used ingredient in skin care alternative to the more traditional topical corticosteroids
products and topical pharmaceuticals ever since. Petrolatum used in dermatologic therapy. The barrier repair creams can
has never been duplicated synthetically. Some barrier repair be used as steroid-sparing aids or to maintain barrier health
creams contain petrolatum as their primary ingredient once the prescription drugs have been discontinued. The
(Eletone, Ferndale Laboratories, Ferndale, MI). Petrolatum main question is whether these more expensive 510(k) barrier
remains the gold standard for barrier repair ingredients devices provide anything that is currently not available in the
because it is the substance closest to the natural intercellular OTC moisturizing market. All of the ingredients that are used
lipids and it can intercalate into the intercellular spaces. 14 in the device creams are found in cosmetic formulations.
These barrier devices are not drugs; they are simply devices
that must be obtained with a prescription.
Dimethicone
A newer alternative to petrolatum as a barrier repair
ingredient is dimethicone, one of a family of silicone oils. Conclusions
These oils are less greasy than petrolatum and possess better
aesthetics, but are not as efficacious as petrolatum in An intact skin barrier is essential for skin health. All
reducing TEWL. Silicone originates from silica, which is dermatologic diseases are due to barrier defects, ranging
found in sand, quartz, and granite. It derives its properties from mild to severe. Barrier repair creams do not actually
from the alternating silica and oxygen bonds, known as repair the barrier, but rather, create an environment optimal
siloxane bonds, which are exceedingly strong. These strong for healing. They contain occlusive ingredients to retard
bonds account for the tremendous thermal and oxidizing TEWL, humectants to attract water to the epidermis, and
stability of silicone. Silicone is resistant to decomposition other assorted ingredients to decrease inflammation, reduce
from ultraviolet radiation, acids, alkalis, ozone, and electrical itching, and provide materials to simulate the intercellular
348 Z.D. Draelos
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