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DR MANJULATA DASH
ASSOCIATE PROFESSOR, DEPARTMENT OF SKIN & VD
GOVT. MEDICAL COLLEGE, KEONJHAR, ODISHA
 About Me
HOD Govt Medical College, Keonjhar, Odisha
Post graduate teacher with 17 years of experience
President, IADVL Odisha State Branch
Former Secretary of IADVL Odisha State Branch
Organizing secretary PGCON East
Organizing secretary CUTICON 2021
Number of publications in national and international journals
Presented papers in national & international conferences
Areas of Interest:
Clinical Dermatology & Dermato Surgery
Comprehensive Moisturising Care
in
Dermatology
1
Dr. Manjulata Dash
Associate Professor, Dermatology
Govt. Medical College, Keonjhar
Moisturisers
• Moisturisers bridge the gap between Basic
Cosmetics (consumer goods) & Medicine
(pharmacological formulations)
• It is a product widely used for normal skin, dry
skin and also diseased skin
• Primary function of a moisturiser is to
suppress moisture loss and maintain skin
homeostasis
The skin is a large, complex organ with a multitude of functions, including barrier,
immunity and sensation.
Epidermis
Dermis
Hypodermis
Keratino
cyte
EPIDERMIS
Skin
Lipid Lamellae
Ceramide: cholesterol:
fatty acids
Cornified
envelope
Lipid delivery
& processing
A Healthy Skin Barrier
Intact corneodesmosomes
Degradatory
proteases
Protease
inhibitors
3/3/2024 Danby SG & Cork MJ, The Academic Unit of Dermatology Research, The University of Sheffield. 7
Swelled
corneocytes
Filaggrin
NMF
H2O
NMF
H2O
NMF
H2O
Natural moisturizing
factor
Urocanic acid, Pyrrolidone
carboxylic acid, lactic acid,
urea
pH
5.5
7
Skin Barrier - Ceramides
A “brick and mortar” model, constitutes
a major barrier function of the stratum
corneum,
The “bricks” - keratinocytes
(corneocytes)
The “mortar” - intercellular lipids
arranged into lamellar layers consisting
of cholesterol, free fatty acids, ceramides
(CERs)
CERs are the main lipids in the stratum
corneum, which play a key role on the
barrier function.
Skin Barrier damage, Dry skin and itch
Skin becomes dehydrated when the stratum corneum is unable to retain water
and loses moisture faster than it is replenished.
Xerosis refer to the concept of dry skin; Barrier dysfunction results in an increase
in transepidermal water loss (TEWL)
Differences between Hydrated Skin
and Dry Skin
Compared to dry and normal skin, ceramide I, II, III, IV, V and VI
diminish with dryness.
Ceramides facilitate epidermal differentiation by re-establishing the
cellular lipids.
Kahraman E. Recent Advances on Topical Applicationof Ceramides to Restore Barrier Function of Skin. Cosmetics 2019, 6, 52; doi:10.3390/cosmetics6030052.
Skin Dehydration & Lost Ceramides
Skin Dehydration & Hyperosmotic stress
• Keratinocytes when dehydrated, the impacts are:
↓ Cell growth
↓ Migration
↓ Differentiation
↓ Cell function Osmotic stress leading to dehydrated keratinocytes
• When the barrier is breached, extracellular
water leaves the skin. This inevitably creates a
hyperosmotic extracellular milieu in the
epidermis, thus creating an osmotic driving
force for the egress of intra-cellular water
Hydrated keratinocytes
Hyperosmotic stress
Dehydration
Aging
Dehydrated keratinocytes
El-ChamiC, Haslam IS, Steward MC, O'Neill CA. Role of organic osmolytes in water homoeostasis in skin. Exp Dermatol. 2014 Aug;23(8):534-7. doi: 10.1111/exd.12473. PMID: 24942488
Skin dehydration & Tight Junction Protein
• Tight junction integrity is of great importance
• Natural moisturising factors (NMFs), glycerol and
aquaglyceroporin AQP3 and presence of tight
junctions are also involved in maintaining optimal
water levels in skin.
El-Chami C, Haslam IS, Steward MC, O'Neill CA. Role of organic osmolytes in water homoeostasis in skin. Exp Dermatol. 2014 Aug;23(8):534-7. doi: 10.1111/exd.12473. PMID: 24942488.
Loss of integrity of the barrier function
is a central factor in the development of
dry skin conditions.
Indian J Dermatol Venereol Leprol . 2003 Mar-Apr;69(2):69-75.
Xerosis or Dry Skin or Asteatosis
ICD 10 :The condition is characterized by decreased quantity
and/ or quality of lipids and/or hydrophilic substances (the latter
is referred to as natural moisturizing factor).
ICD 11 : Defines xerosis cutis/asteatosis (code ED 54) as a
condition usually caused by a lack in epidermal lipids (as of May
2018).
Disease subgroups listed in the ICD 11 include atopic
xeroderma, asymptomatic or pruritic xerosis cutis,
asteatosis and senile xerosis.
How does it manifest?
Decreased elasticity
Coarsening of its texture
Wrinkling
Erythema
Fissures.
A feeling of tightness and
pruritus
Perceived as pain or a
burning sensation by
some patients.
Pathogenesis for Dry Skin Conditions
• Altered composition of the intercellular lipid bilayer, e.g.,
caused by external or endogenous factors .
• Abnormal keratinocyte differentiation or desmolysis, e.g.,
in psoriasis, ichthyosis and others.
• Decreased content of moisturizing factors in the skin
e.g., caused by environmental factors , fluid deficiency or
by decreased endogenous production (e.g., inherited
filaggrin deficiency) or poor distribution (e.g., aquaporin 3
deficiency).
Introduction to moisturisers
 Moisturiser and emollient are often used
synonymously.
 occlusives and humectants are also part of it.
 Emmolients are lipids that enhance skin hydration,
smoothness, softness, flexibility.
 Occlusives are oil based and create a hydrophobic
barrier to block the TEWL.
 Humectants are hygroscopic that attract water
from dermis and gives a humid environment into
the epidermis.
Role of
Moisturizers
Moisturizing
action
Anti-
inflammatory
action
Antipruritic
action
Antimitotic
action
Misc. Action
(Wound
healing)
Photo
protective
action
Clin Med Res. 2017 Dec; 15(3-4): 75–87.
Characteristics of Moisturisers
The IDEAL
Topical Moisturisers
• Cosmetic Benefits
• Therapeutic
benefits
Provides immediate skin hydration and
prevents TEWL
Contains no soap, fragrance, colours
or common irritants
Affordable, cosmetically elegant and
acceptable
Eases itching and inflammation
and relieves irritation and
soreness
Rapid absorption, non-comedogenic,
long-lasting and pH balanced
1
2
3
4
5
Protects the skin and restores
lipid barrier
7
Soften dry and cracked skin,
and reduces scaling
6
http://dx.doi.org/10.5772/intechopen.101964
EMOLLIENTS
Saturated/ unsaturated
hydrocarbons-resemble natural
lipids
Restore barrier function,
membrane fluidity and cell
signaling
Skin hydration, smoothness,
textural improvement
Lauric Acid, linoleic acid, linolenic
acid, oleic acid, stearic acid
HUMECTANTS
LMW substances -attract water into
SC Resemble Intercellular lipid
bilayers
Urea, sorbitol, panthenol, glycerol,
propylene glycol, hyaluronic acid,
alpha hydroxy acids
Hygroscopic substances that attract
water from the environment &
dermis
Increase the water content (turgor)
of the epidermis
Decrease erythema, scaling
Anti-pruritic
Anti-microbial
Anti-inflammatory
Shorten episodes, prevent flares and relapse
Types of Moisturizers
Cosmetics 2022, 9, 61
OCCLUSIVES
Oils and waxes- resemble Natural
Moisturizing Factor
Mineral oil, petrolatum jelly,
beeswax, silicones, paraffin, lanolin,
squalene
Form an inactive, hydrophobic layer
and prevent TEWL
Maintain skin water content and
hydration
Active ingredients of moisturisers in preference
to Dry skin
JDDG. 2018; 16 (Suppl. 4): 3-35.
Active ingredients of moisturisers in preference to Dry
skin
JDDG. 2018; 16 (Suppl. 4): 3-35.
How to choose a formulation?
Topical bases are divided into four groups:
1. Oil-in-water (hydro) lotion
2. Water-in-oil (lipo)lotion
3. Hydrophilic
4. Lipophilic creams.
Water-in-oil lotions or lipophilic creams are better suited for dry skin, as their bases prevent increased
water loss, resulting in improved hydration.
While pure oils/fats may generally be recommended for scale removal, they are not suited as bases or
for long-term basic skin care.
For acute, inflammatory disease stages or intense pruritus, bases with a higher water content are
preferable
Moisturisers – side effects
Adverse effect Plausible causes
Subjective irritation Humectants e.g., lactic acid, urea, preservatives
Irritant reactions Proteins in vegetable oils, urea, hydroxyl acids, propylene glycol,
solvents
Allergic contact dermatitis Lanolin, propylene glycol, vitamin E, Kathon CG, Preservatives,
fragrances, sunscreens, herbal products
Occlusive folliculitis Petrolatum, mineral oils
Photosensitivity eruptions and
photomelanosis
Fragrances, hydroxyl acids
Cosmetic acne Occlusive oils used in water in oil preparations
Contact urticaria Preservatives e.g. sorbic acid, fragrances
Poisoning in burn patients Propylene glycol
Dermatological Conditions having Dry Skin
Eczema
• Atopic Dermatitis
• Hand Eczema
Disorder of Keratinisation
• Ichthyosis
• Psoriasis
• Palmoplantar
Keratoderma
• Lichen planus
Dermatosis secondary to an
underlying disorders
• Diabetes
• Thyroid disorders
• Pruritus of pregnancy
Damaged skin integrity in special
populations
• Elderly
• Neonates & infants
• Amputee & bed ridden patients
Other Dermatologic disorders
• Acne Vulgaris
• Rosacea
• Xerosis
• Contact dermatitis
Indian J Dermatol. 2016 May-Jun; 61(3): 279–287.
Skin Barrier Dysfunction & Skin Diseases
Atopic Dermatitis
- Genetic Mutation in Skin structural protein – filaggrin
- Filaggrin deficiency leads to skin barrier defect
Increased trans epidermal water loss
Facilitates exposure to environmental allergen &
infective organisms
Persistent skin inflammation
Moisturiser for Atopic Dermatitis
1. Natural Oils  high linoleic acid & low oleic acid ratio
•Safflower oil, Sunflower seed oil are natural oils with
highest linoleic acid & oleic acid ratio
•Olive oil having  low linoleic acid & oleic acid ratio 
deteriorate skin barrier
2. Humectant
•10% Urea  reduce trans-epidermal water loss
 reduce skin irritation from sodium lauryl
sulfate exposure in both atopic & normal skin
•Glycerine  rapid hydration
•Lactic acid  L-isomer  stimulates ceramide synthesis
Moisturiser for Atopic Dermatitis contd..
New concept
- Topical mixtures of three key stratum corneum lipids
consisting of ceramide, cholesterol & free fatty acid in optimal
proportion (3:1:1)  accelerate barrier repair
- Anti inflammatory agent incorporated with emollient or
humectant provide additional barrier repair & control
inflammation
Aloevera
Bisabolol
Shea Butter
Glycerrhetinic acid (licorice root)
Niacinamide
Zinc Gluconate
Moisturizers are effective
at prolonging remission
and reducing risk of
relapse
Seborrheic Dermatitis
- Alternation of corneodesmosomal hydrolysis
- Impaired lipid organisation
- Electron Microscopy finding
- Corneocyte shape & corneodesmosome
alteration
- Intercellular Malassezia species
- Biochemical analysis ceramides & alteration of
SC protein acid profile in absence of apparent
inflammation
- These evidence emphasize crucial role of barrier
restoration & maintenance in management of
seborrheic dermatitis
Moisturiser for Seborrheic Dermatitis
Non Steroidal topical device Cream
It is a water based fragrance free Cream approved by US
Food & Drugs administration as medical device to manage &
relieve Seborrheic Dermatitis symptoms such as itches,
erythema, scaling & pain
Ingredients  piroctone olamine, multiple antioxidants
(telmesteine tocopheryl acetate, ascorbil tetra iso pamitate),
multiple skin conditioning agents  ethyl hexyl palmitate,
bisabolal, shea butter, vitis vinifera
Moisturiser for Contact Dermatitis
 Lipid rich moisturisers
 Overnight application
 Ointments preferred over creams
 Simple petroleum based emollients
 Topical mixture of stratum corneum lipids including
ceramides
 Keratolytic (salicylic acid), urea  hyper keratotic
dermatitis
 Urea  makes less susceptible against irritation to
sodium lauryl sulphate
 Canola oil  also ameliorate reaction to sodium lauryl
sulphate
Moisturiser for Contact Dermatitis contd…
 Essential fatty acid (linoleic & alpha linoleic) affects skin
barrier function, membrane fluidity, eicosanoid production,
cell signalling
 Restoration of damaged epidermal barrier and skin
hydration important for prevention of chronic contact
dermatitis
 Gutman et al – soak & smear (application of mild to high
potency topical steroid ointment & emollient over a
damped skin) (lock in moisture)
Moisturiser for Acne
Topical therapies, such
as benzoyl peroxide,
retinoids, antibiotics with
alcohol-based
preparations, and
salicylic acid, can cause
skin irritation resulting in
a lack of patient
adherence
Squalane as Moisturiser
Squalene is most commonly produced sebum component
Production slows after 30  dryness
Sqalane is a saturated form of sqalene, oxidation resistant,
good as moisturiser
Less greasy, odourless, non comedogenic, anti bacterial,
safe for sensitive skin
Conventional Moisturizers GAP
1. No Intra-cellular keratinocytes hydration -
> Leads to Cell Shrinkage
2. No Production of Tight Junction proteins OCCLUDIN -
> Increases TEWL
3. Does not Replenish all lost Ceramide types- Ceramide type 1,2,3,4,5,6 II
> Compromise Skin barrier
4. Non-Effective Humectant( Hyaluronic Acid) with higher molecular weight
> Compromise in Regulation of moisturization
Novel approach in Dry skin disorder
A new generation of naturally
hydrating active ingredients extracted
from a variety of Australian Hibiscus,
selected for its high natural betaine
content.
Stimulates organic osmolytes cellular
intake and improves the skin barrier
function to reduce water loss by
increasing lipid production.
Hydrosella™
Novel approach in Dry skin disorder that targets
Intra-cellular Moisturization
Hydrosella™
Hydrosella™ is standardized in
betaine, a natural organic osmolyte
Betaine osmolytes an osmotic
stimulus or UV exposure to protect
keratinocytes from cell damage,
maintain protein integrity and
restore cell volume .
Keratinocytes
Hyperosmoticstress a
UV
. Z'
0
Keratinocyteslose
intracellular water
and shrink
Production of Organic
osmolytes and
Improved cell volume
Burg, Maurice & Ferraris, Joan. (2008). Intracellular Organic Osmolytes: Function and Regulation. The Journal of biologicalchemistry. 283.7309-13.10.1074/jbc.R700042200.
Clinical Studies
12
Clinical Studies
Effect on Organic Osmolyte Transporter
EFFECT ON ORGANIC OSMOLYTE TRANSPORTER
EVALUATION OF OSMOLYTE TRANSPORTER
3<OOO1J
Protocol
• Human keratinocytes
• Betaine content of Hydrosella"*at 0.2% is ± 4 uM
• Cells incubated during 24 h in absence (control) or in presence of increasing concentrations of Hydrosella™
• Intracellular organic osmolyte transporter (TauT) quantified by ELISA assay
Hydrosella™ significantly increases intracellular TauT, with
greater response than pure Betaine
re
Clinical Studies
Effect on Organic Osmolyte Transporter
EVALUATION OF OSMOLYTE TRANSPORTER
r
X y
Betaine 20pM
Nuclei and TauT
Hydrosella™ 0.4%
Nuclei and TauT
TauT
expression in
green
Untreated I
Nuclei and TauT
Hydrosella™ significantly increases osmolyte transporter,
helping the skin natural osmolyte defense system -------—---------
-- • ■--------
Protocol
• Human skin explant from a 43 and 44 years old Caucasian female
• Application of Hydrosella™ at 0.4% or Betaine at 5 or 20pM for 48h
• Betaine content of Hydrosella™at 0.4% is ± 5pM
• Evaluation of organic osmolytes transporter content by immunostaining (green labelling)
r.
Protocol
• Human skin explant from a 43 and 44 years old Caucasian female
• Application of Hydrosella™ at 0.4% or Betaine at 5 or 20|iM for 48h
• Betaine content of Hydrosella™at 0.4% is ± 5pM
• Evaluation of organic osmolytes transporter content by immunostaining (green labelling)
TO
Clinical Studies
Effect on Cell Total Volume Recovery
EVALUATION OF CELL VOLUME RECOVERY EVALUATION OF TOTAL CELL VOLUME RECOVERY (%)
Protocol
• Normal human epidermal keratinocytes (NHEKs) from 3 different donors
• NHEKs were seeded at single cell density and exposed to 5 minutes in isoosmotic conditions, 15 minutes hyperosmotic conditions
and 15 minutes in isoosmotic conditions, in absence (control) or presence of Hydrosella™ 0.2%
• NHEKS were treated with Calcein green for visualizationby live cell imaging
Protocol
• Normal human epidermal keratinocytes (NHEKs) from 3 different donors
• NHEKs were seeded at single cell density and exposed to 5 minutes in isoosmotic conditions, 15 minutes hyperosmotic conditions and 15 minutes in
isoosmotic conditions, in absence (control) or presence of Hydrosella™ 0.2%
• NHEKS were treated with Calcein green for visualizationby live cell imaging
f>
Hydrosella™ improves keratinocytes volume recovery
I_______________________________________________________________________________________=______________________>
0 Untreated 0 Hydrosella'" 0.2% Test made at The of Manchester
Clinical Studies
Preventive Effect on Neutral Lipids
0 Untreated DO £ Defipidated Q Dellpidated+ Hydrosella'" 1%
Neutral lipid
expression ir
Protocol
• Human skin explant from a 34 years old Caucasian female
• Explants were incubated with Hydrosella™1% or without (control)
• Hydrosella™was appliedon skin explants on DO, D2 and D3 before delipidation
• Delipidation made with ether/acetone solution (1:1)
• Evaluation by lipid staining with LipidTox™ green neutral lipid at DO, D3 and Db
EVALUATION OF PREVENTIVE EFFECT
OF HYDROSELLA1" ON LIPID CONTENT
z
Hydrosella™ provides a preventive action for skin lipid
X
____________
protection and increases its production
J
16
Clinical Studies
Curative Effect on Neutral Lipids
0 Untreated DO 0 Delipidated f Delipidated * Hydrosella"-1%
Neutral lipids
expression in
green
Protocol
120- §
o
-
Q
=
5
c
*
5
?
• Human skin explant from a 34 years old Caucasian female
• Pre-cultures for 3 days, then delipidated with ether/acetone solution (1:1)
• Hydrosella™ 1% was applied or not (control) once on skin explants
• Evaluation by lipid staining with LipidTox™ green neutral lipid (T3h, DI, D2)
[3 DAYS PRE-
CULTURE DO D0*3H DI D2 1
1 1
••• •
• |
(-------------------------------------------------------------------------------------------------------------------------------------
Hydrosella™ increases skin lipid production following
dehydration to prevent further water loss
Clinical Studies
Effect on Stratum Corneum Thickness
Protocol
• Human skin explant from a 34 years old Caucasian female
• Pre-cultures for 3 days, then delipidated with ether/acetone solution
(1:1)
• Hydrosella™ 1% was applied or not (control) once on skin explants
• Evaluation by microscopical observation at T3h, DI and D2
EVALUATION OF STRATUM COONCUM THICKNESS FOLLOWING DEUPIDATION
[ 3 DAYS PRE-
CULTURE DO DO*3H DI
D2 ]
rz ••• *± * • J
Deapdatton f Eiplants sanping f FWOud appteabor
, ___________________________•p <0.05," p
<001, — p <0.001
• Untreated f Centro! Q Hyttoselia" 1%
Hydrosella™ enhances the stratum corneum thickness
to maintain a well-hydrated skin
Clinical Studies
Evaluation of Skin Water Content
Protocol
• 10 female volunteers with normal to dry skin
• 1 application on forearm of Hydrosella™1%
• Evaluation of skin moisturizing by Corneometer
• Placebo f Hydrosella ' 1%
f-----------------------------------------------------------------------------------------------------------X
Hydrosella™ rapidly increases skin moisture content with a continuous
effect up to 72hrs after single application
< ■ ■ - - >
INGREDIENTS INCI NAMES
ACTIVE
FORMULA (%)
PLACEBO
(%)
Dciornzed Water Water 97.00 97.40
Glycerin Glycerin 060 120
Carbopol ultrez 21 Acrylates/C10-30Alkyl Acrylate 050 050
Crosspolymer
Chiorphenesin Chiorphenesin 0.30 0.30
Phenoxyethanol Phenoxyethanol 0.60 060
Hydrosella'" Glycerin(and) Water (and) 1.00 000
Erythrito1 (and) Hibiscus
Sabda’if'a
Fruit Extract —
EVALUATION OF SKIN HYDRATION AFTER SINGLE APPucATioua^k.
Tlh T24h T4Sti T72h
"D<001.“p<0001
19
Clinical Studies
Evaluation of Skin Water Loss
Protocol
• 10 female volunteers with normal to dry skin
• 1 application on forearm of Hydrosella™1%
• Evaluation of skin water loss by TEWL
Tlh T24h T48h T72h
______________________“*p<0001
>
• Placebo Q Hydrosella' 1%
f INGREDIENTS
INCI NAMES ACTIVE
FORMULA (%)
PLACEBO |
(%)
Deionized Water Water 97.00 97.40
Glycerin Glycerin 060 120
Cart spot ultre2 21 Acrylates/C1O-3OAlkyl Acrylate
Crosspolymer
0.50 0 50
Chlorohenesm CNorphenesm 0.30 0.30
Phenoxyethanol Pbencxyetoanol 0.60 0.60
Hydrosella- Glycerin(and) Water (and)
Erythritol (and) Hibiscus
SabdariffaFruit Extract
1.00 000
(----------------------------------------------------------------------------------------------
Hydrosella™ rapidly decreases skin water loss with a continuous
effect up to 72hrs after single application
Novel approach in Dry skin disorder that targets
Inter-cellular Moisturization
Hydrosella™ is standardized in betaine, a natural
organic osmolyte
Helps to increases production of tight junction
protein Occludin ,thereby reduces Trans Epidermal
Water Loss(TEWL)
Increases production of
Tight Junction Protein Occludin2
Reduces
TEWL
21
Clinical Studies
Curative effect on Occludin Production
CURATIVE EFFECT ON OCCLUDIN PRODUCTION
Protocol
• Human skin explant from a 34 years old Caucasian female
• Pre-cultures for 3 days, then dellpidated wrth ether/acetone solution (1:1)
• Hydrosella"* 1* was applied or not (control) once on skin explants
• Evaluation by immunostaining and microscopical observation
3 hours after delipidation
T>HConqpl
’ T3h ’-HydrcneU*’’ • 1%
Hydrosella’" increases tight junction proteins expression (occludin) to restore and to improve skin
barrier function
02
Novel approach in Dry skin disorder that targets
Inter-cellular Moisturization
Replenish the Lost Ceramides
Significance of Ceramides
Compared to dry and normal skin, ceramide I, II, III, IV, V and VI diminish with
dryness, while CERs are at a high level in normal skin
Forming intercellular lipid lamellar structures is an important factor for the
formation of an effective barrier to reduce TEWL.
Scientific Article
“CERs are the main lipids in the
stratum corneum, which play a key role
on the barrier function"
“Compared to dry and normal skin,
ceramide I, II, III, IV, V and VI diminish
with dryness, while CERs are at a high
level in normal skin".
cosmetics IMDPIJ
Review
Recent Advances on Topical Application of Ceramides
to Restore Barrier Function of Skin
Emine Kahraman, Melis Kavkin, Hurnevra Sahin Beklav and Scvgi Gungor' Department
<>f Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University. 34116
Beyazit, Turkey • Correspondence sgungorihstanbuledu.tr
chKk
lor Received: 3U |une 21H9; Accepted: 17 August 2019; Published: 20 August 2019
l»4«t»l
Abstract: Human skin is the largest organ of the body and is an effective physical barrier keeping it
from environmental conditions. This barrier function of the skin is based on stratum corneum, located in
the uppermost skin. Stratum ameum has corneocytes surrounded by multilamellar lipid membranes
which an1 composed of cholesterol, frw fatty acids and ceramides (CFRsl Alterations in ceramide
content of the stratum ameum are associated with numerous skin disorders. In recent years, CERs have
been incorporated into conventional and novel carrier systems with the purpose of exogenously applying
CERs to help the barrier function of the skin. This rev iew provides an overview of the structure,
function and importance of CERs to restore the barrier function of tire skin following their topical
application.
Keywords: skin barrier; skin disorders; ceramides; topical application
1. Skin Barrier
Human skin is the largest organ of the body, accounting tor 16% of total weight and having an
area of 1.8 m*. It prevents excessive water loss from the body and helps to maintain electrolyte balance
and involves some metabolic processes that are related to immune system. It also protects the organism
against microorganisms, ultraviolet radiation, toxic substances and mechanical damage, creating a
physical barrier between environmental conditions and the body. Basically, the human skin is a multi-
layered membrane From deep to superficial these layers are (Figure 1) |lf
Cosmetics 2019, 6, 52; doi:10.3390/cosmetics6030052.
Novel approach in Dry skin disorder that targets
Regulation of Moisturization
Importance of Hyaluronic Acid (PrincipHyal 800-1000)
HA - a biologic humectant, can penetrate into the stratum corneum if it is of the
correct size
Topical HA suitable for all Fitzpatrick skin types
Moisturizing and anti-ageing effects which help in skin regeneration and smooths
the skin
Draelos ZD, Diaz I, Namkoong J, Wu J, Boyd T. Efficacy Evaluation of a Topical Hyaluronic Acid Serum in Facial Photoaging. Dermatol Ther (Heidelb). 2021 Aug;11(4):1385-1394. doi: 10.1007/s13555-021-
00566-0. Epub 2021 Jun 26. PMID: 34176098; PMCID: PMC8322246. . Juncan AM, Moisa DG, Santini A, Morgovan C, Rus LL, Vonica-Tincu AL, Loghin F. Advantages of Hyaluronic Acid and Its Combination
with Other BioactiveIngredients in Cosmeceuticals. Molecules. 2021 Jul 22;26(15):4429. doi: 10.3390/molecules26154429. PMID: 34361586; PMCID: PMC8347214
Novel approach in Dry skin disorder that targets
Regulation of Moisturization
Reduces TEWL
Maintains skin
hydration
Skin protection by
forming viscoelastic film
Importance of Hyaluronic Acid (PrincipHyal 800-1000)
Cuticle
PRODUCT CLASSIFICATION FUNCTIONS
AmviHyaP* 800-1000 kDa
Medium molecular weight-HA
(MMW-HA)
• Maintains skin hydration
• Softens the Skin
Draelos ZD, Diaz I, Namkoong J, Wu J, Boyd T. Efficacy Evaluationof a Topical Hyaluronic Acid Serum in Facial Photoaging. Dermatol Ther (Heidelb). 2021 Aug;11(4):1385-1394. doi: 10.1007/s13555-021-
00566-0. Epub 2021 Jun 26. PMID: 34176098; PMCID: PMC8322246.
. Juncan AM, Moisa DG, Santini A, Morgovan C, Rus LL, Vonica-TincuAL, Loghin F. Advantages of Hyaluronic Acid and Its Combinationwith Other BioactiveIngredients in Cosmeceuticals. Molecules.
2021 Jul 22;26(15):4429. doi: 10.3390/molecules26154429. PMID: 34361586; PMCID: PMC8347214
Take home message:
 Till date choosing, the right moisturizer is still a matter of trial
and error.
 Numerous cosmetics are being released by a variety of
cosmetic companies today, and in particular, moisturizers are
used not only for patients suffering from skin diseases but also
for people with normal skin.
 The key to future moisturizer therapy will be to tailor specific
agents to specific dermatological needs.
 Knowing the in and out of the actives and their interactions
with the skin will help better usage and efficacy of the
available moisturizers.
Thank You
27

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Comprehensive Moisturising care in Dermatology-REVISED-1.pptx

  • 1. DR MANJULATA DASH ASSOCIATE PROFESSOR, DEPARTMENT OF SKIN & VD GOVT. MEDICAL COLLEGE, KEONJHAR, ODISHA  About Me HOD Govt Medical College, Keonjhar, Odisha Post graduate teacher with 17 years of experience President, IADVL Odisha State Branch Former Secretary of IADVL Odisha State Branch Organizing secretary PGCON East Organizing secretary CUTICON 2021 Number of publications in national and international journals Presented papers in national & international conferences Areas of Interest: Clinical Dermatology & Dermato Surgery
  • 2. Comprehensive Moisturising Care in Dermatology 1 Dr. Manjulata Dash Associate Professor, Dermatology Govt. Medical College, Keonjhar
  • 3. Moisturisers • Moisturisers bridge the gap between Basic Cosmetics (consumer goods) & Medicine (pharmacological formulations) • It is a product widely used for normal skin, dry skin and also diseased skin • Primary function of a moisturiser is to suppress moisture loss and maintain skin homeostasis
  • 4.
  • 5.
  • 6. The skin is a large, complex organ with a multitude of functions, including barrier, immunity and sensation. Epidermis Dermis Hypodermis Keratino cyte EPIDERMIS Skin
  • 7. Lipid Lamellae Ceramide: cholesterol: fatty acids Cornified envelope Lipid delivery & processing A Healthy Skin Barrier Intact corneodesmosomes Degradatory proteases Protease inhibitors 3/3/2024 Danby SG & Cork MJ, The Academic Unit of Dermatology Research, The University of Sheffield. 7 Swelled corneocytes Filaggrin NMF H2O NMF H2O NMF H2O Natural moisturizing factor Urocanic acid, Pyrrolidone carboxylic acid, lactic acid, urea pH 5.5 7
  • 8. Skin Barrier - Ceramides A “brick and mortar” model, constitutes a major barrier function of the stratum corneum, The “bricks” - keratinocytes (corneocytes) The “mortar” - intercellular lipids arranged into lamellar layers consisting of cholesterol, free fatty acids, ceramides (CERs) CERs are the main lipids in the stratum corneum, which play a key role on the barrier function.
  • 9. Skin Barrier damage, Dry skin and itch Skin becomes dehydrated when the stratum corneum is unable to retain water and loses moisture faster than it is replenished. Xerosis refer to the concept of dry skin; Barrier dysfunction results in an increase in transepidermal water loss (TEWL) Differences between Hydrated Skin and Dry Skin
  • 10. Compared to dry and normal skin, ceramide I, II, III, IV, V and VI diminish with dryness. Ceramides facilitate epidermal differentiation by re-establishing the cellular lipids. Kahraman E. Recent Advances on Topical Applicationof Ceramides to Restore Barrier Function of Skin. Cosmetics 2019, 6, 52; doi:10.3390/cosmetics6030052. Skin Dehydration & Lost Ceramides
  • 11. Skin Dehydration & Hyperosmotic stress • Keratinocytes when dehydrated, the impacts are: ↓ Cell growth ↓ Migration ↓ Differentiation ↓ Cell function Osmotic stress leading to dehydrated keratinocytes • When the barrier is breached, extracellular water leaves the skin. This inevitably creates a hyperosmotic extracellular milieu in the epidermis, thus creating an osmotic driving force for the egress of intra-cellular water Hydrated keratinocytes Hyperosmotic stress Dehydration Aging Dehydrated keratinocytes El-ChamiC, Haslam IS, Steward MC, O'Neill CA. Role of organic osmolytes in water homoeostasis in skin. Exp Dermatol. 2014 Aug;23(8):534-7. doi: 10.1111/exd.12473. PMID: 24942488
  • 12. Skin dehydration & Tight Junction Protein • Tight junction integrity is of great importance • Natural moisturising factors (NMFs), glycerol and aquaglyceroporin AQP3 and presence of tight junctions are also involved in maintaining optimal water levels in skin. El-Chami C, Haslam IS, Steward MC, O'Neill CA. Role of organic osmolytes in water homoeostasis in skin. Exp Dermatol. 2014 Aug;23(8):534-7. doi: 10.1111/exd.12473. PMID: 24942488.
  • 13. Loss of integrity of the barrier function is a central factor in the development of dry skin conditions. Indian J Dermatol Venereol Leprol . 2003 Mar-Apr;69(2):69-75.
  • 14. Xerosis or Dry Skin or Asteatosis ICD 10 :The condition is characterized by decreased quantity and/ or quality of lipids and/or hydrophilic substances (the latter is referred to as natural moisturizing factor). ICD 11 : Defines xerosis cutis/asteatosis (code ED 54) as a condition usually caused by a lack in epidermal lipids (as of May 2018). Disease subgroups listed in the ICD 11 include atopic xeroderma, asymptomatic or pruritic xerosis cutis, asteatosis and senile xerosis.
  • 15. How does it manifest? Decreased elasticity Coarsening of its texture Wrinkling Erythema Fissures. A feeling of tightness and pruritus Perceived as pain or a burning sensation by some patients.
  • 16. Pathogenesis for Dry Skin Conditions • Altered composition of the intercellular lipid bilayer, e.g., caused by external or endogenous factors . • Abnormal keratinocyte differentiation or desmolysis, e.g., in psoriasis, ichthyosis and others. • Decreased content of moisturizing factors in the skin e.g., caused by environmental factors , fluid deficiency or by decreased endogenous production (e.g., inherited filaggrin deficiency) or poor distribution (e.g., aquaporin 3 deficiency).
  • 17. Introduction to moisturisers  Moisturiser and emollient are often used synonymously.  occlusives and humectants are also part of it.  Emmolients are lipids that enhance skin hydration, smoothness, softness, flexibility.  Occlusives are oil based and create a hydrophobic barrier to block the TEWL.  Humectants are hygroscopic that attract water from dermis and gives a humid environment into the epidermis.
  • 19. Characteristics of Moisturisers The IDEAL Topical Moisturisers • Cosmetic Benefits • Therapeutic benefits Provides immediate skin hydration and prevents TEWL Contains no soap, fragrance, colours or common irritants Affordable, cosmetically elegant and acceptable Eases itching and inflammation and relieves irritation and soreness Rapid absorption, non-comedogenic, long-lasting and pH balanced 1 2 3 4 5 Protects the skin and restores lipid barrier 7 Soften dry and cracked skin, and reduces scaling 6 http://dx.doi.org/10.5772/intechopen.101964
  • 20. EMOLLIENTS Saturated/ unsaturated hydrocarbons-resemble natural lipids Restore barrier function, membrane fluidity and cell signaling Skin hydration, smoothness, textural improvement Lauric Acid, linoleic acid, linolenic acid, oleic acid, stearic acid HUMECTANTS LMW substances -attract water into SC Resemble Intercellular lipid bilayers Urea, sorbitol, panthenol, glycerol, propylene glycol, hyaluronic acid, alpha hydroxy acids Hygroscopic substances that attract water from the environment & dermis Increase the water content (turgor) of the epidermis Decrease erythema, scaling Anti-pruritic Anti-microbial Anti-inflammatory Shorten episodes, prevent flares and relapse Types of Moisturizers Cosmetics 2022, 9, 61 OCCLUSIVES Oils and waxes- resemble Natural Moisturizing Factor Mineral oil, petrolatum jelly, beeswax, silicones, paraffin, lanolin, squalene Form an inactive, hydrophobic layer and prevent TEWL Maintain skin water content and hydration
  • 21. Active ingredients of moisturisers in preference to Dry skin JDDG. 2018; 16 (Suppl. 4): 3-35.
  • 22. Active ingredients of moisturisers in preference to Dry skin JDDG. 2018; 16 (Suppl. 4): 3-35.
  • 23. How to choose a formulation? Topical bases are divided into four groups: 1. Oil-in-water (hydro) lotion 2. Water-in-oil (lipo)lotion 3. Hydrophilic 4. Lipophilic creams. Water-in-oil lotions or lipophilic creams are better suited for dry skin, as their bases prevent increased water loss, resulting in improved hydration. While pure oils/fats may generally be recommended for scale removal, they are not suited as bases or for long-term basic skin care. For acute, inflammatory disease stages or intense pruritus, bases with a higher water content are preferable
  • 24. Moisturisers – side effects Adverse effect Plausible causes Subjective irritation Humectants e.g., lactic acid, urea, preservatives Irritant reactions Proteins in vegetable oils, urea, hydroxyl acids, propylene glycol, solvents Allergic contact dermatitis Lanolin, propylene glycol, vitamin E, Kathon CG, Preservatives, fragrances, sunscreens, herbal products Occlusive folliculitis Petrolatum, mineral oils Photosensitivity eruptions and photomelanosis Fragrances, hydroxyl acids Cosmetic acne Occlusive oils used in water in oil preparations Contact urticaria Preservatives e.g. sorbic acid, fragrances Poisoning in burn patients Propylene glycol
  • 25. Dermatological Conditions having Dry Skin Eczema • Atopic Dermatitis • Hand Eczema Disorder of Keratinisation • Ichthyosis • Psoriasis • Palmoplantar Keratoderma • Lichen planus Dermatosis secondary to an underlying disorders • Diabetes • Thyroid disorders • Pruritus of pregnancy Damaged skin integrity in special populations • Elderly • Neonates & infants • Amputee & bed ridden patients Other Dermatologic disorders • Acne Vulgaris • Rosacea • Xerosis • Contact dermatitis Indian J Dermatol. 2016 May-Jun; 61(3): 279–287.
  • 26. Skin Barrier Dysfunction & Skin Diseases
  • 27. Atopic Dermatitis - Genetic Mutation in Skin structural protein – filaggrin - Filaggrin deficiency leads to skin barrier defect Increased trans epidermal water loss Facilitates exposure to environmental allergen & infective organisms Persistent skin inflammation
  • 28. Moisturiser for Atopic Dermatitis 1. Natural Oils  high linoleic acid & low oleic acid ratio •Safflower oil, Sunflower seed oil are natural oils with highest linoleic acid & oleic acid ratio •Olive oil having  low linoleic acid & oleic acid ratio  deteriorate skin barrier 2. Humectant •10% Urea  reduce trans-epidermal water loss  reduce skin irritation from sodium lauryl sulfate exposure in both atopic & normal skin •Glycerine  rapid hydration •Lactic acid  L-isomer  stimulates ceramide synthesis
  • 29. Moisturiser for Atopic Dermatitis contd.. New concept - Topical mixtures of three key stratum corneum lipids consisting of ceramide, cholesterol & free fatty acid in optimal proportion (3:1:1)  accelerate barrier repair - Anti inflammatory agent incorporated with emollient or humectant provide additional barrier repair & control inflammation Aloevera Bisabolol Shea Butter Glycerrhetinic acid (licorice root) Niacinamide Zinc Gluconate
  • 30. Moisturizers are effective at prolonging remission and reducing risk of relapse
  • 31. Seborrheic Dermatitis - Alternation of corneodesmosomal hydrolysis - Impaired lipid organisation - Electron Microscopy finding - Corneocyte shape & corneodesmosome alteration - Intercellular Malassezia species - Biochemical analysis ceramides & alteration of SC protein acid profile in absence of apparent inflammation - These evidence emphasize crucial role of barrier restoration & maintenance in management of seborrheic dermatitis
  • 32. Moisturiser for Seborrheic Dermatitis Non Steroidal topical device Cream It is a water based fragrance free Cream approved by US Food & Drugs administration as medical device to manage & relieve Seborrheic Dermatitis symptoms such as itches, erythema, scaling & pain Ingredients  piroctone olamine, multiple antioxidants (telmesteine tocopheryl acetate, ascorbil tetra iso pamitate), multiple skin conditioning agents  ethyl hexyl palmitate, bisabolal, shea butter, vitis vinifera
  • 33. Moisturiser for Contact Dermatitis  Lipid rich moisturisers  Overnight application  Ointments preferred over creams  Simple petroleum based emollients  Topical mixture of stratum corneum lipids including ceramides  Keratolytic (salicylic acid), urea  hyper keratotic dermatitis  Urea  makes less susceptible against irritation to sodium lauryl sulphate  Canola oil  also ameliorate reaction to sodium lauryl sulphate
  • 34. Moisturiser for Contact Dermatitis contd…  Essential fatty acid (linoleic & alpha linoleic) affects skin barrier function, membrane fluidity, eicosanoid production, cell signalling  Restoration of damaged epidermal barrier and skin hydration important for prevention of chronic contact dermatitis  Gutman et al – soak & smear (application of mild to high potency topical steroid ointment & emollient over a damped skin) (lock in moisture)
  • 35. Moisturiser for Acne Topical therapies, such as benzoyl peroxide, retinoids, antibiotics with alcohol-based preparations, and salicylic acid, can cause skin irritation resulting in a lack of patient adherence
  • 36. Squalane as Moisturiser Squalene is most commonly produced sebum component Production slows after 30  dryness Sqalane is a saturated form of sqalene, oxidation resistant, good as moisturiser Less greasy, odourless, non comedogenic, anti bacterial, safe for sensitive skin
  • 37. Conventional Moisturizers GAP 1. No Intra-cellular keratinocytes hydration - > Leads to Cell Shrinkage 2. No Production of Tight Junction proteins OCCLUDIN - > Increases TEWL 3. Does not Replenish all lost Ceramide types- Ceramide type 1,2,3,4,5,6 II > Compromise Skin barrier 4. Non-Effective Humectant( Hyaluronic Acid) with higher molecular weight > Compromise in Regulation of moisturization
  • 38. Novel approach in Dry skin disorder A new generation of naturally hydrating active ingredients extracted from a variety of Australian Hibiscus, selected for its high natural betaine content. Stimulates organic osmolytes cellular intake and improves the skin barrier function to reduce water loss by increasing lipid production. Hydrosella™
  • 39. Novel approach in Dry skin disorder that targets Intra-cellular Moisturization Hydrosella™ Hydrosella™ is standardized in betaine, a natural organic osmolyte Betaine osmolytes an osmotic stimulus or UV exposure to protect keratinocytes from cell damage, maintain protein integrity and restore cell volume . Keratinocytes Hyperosmoticstress a UV . Z' 0 Keratinocyteslose intracellular water and shrink Production of Organic osmolytes and Improved cell volume Burg, Maurice & Ferraris, Joan. (2008). Intracellular Organic Osmolytes: Function and Regulation. The Journal of biologicalchemistry. 283.7309-13.10.1074/jbc.R700042200.
  • 41. Clinical Studies Effect on Organic Osmolyte Transporter EFFECT ON ORGANIC OSMOLYTE TRANSPORTER EVALUATION OF OSMOLYTE TRANSPORTER 3<OOO1J Protocol • Human keratinocytes • Betaine content of Hydrosella"*at 0.2% is ± 4 uM • Cells incubated during 24 h in absence (control) or in presence of increasing concentrations of Hydrosella™ • Intracellular organic osmolyte transporter (TauT) quantified by ELISA assay Hydrosella™ significantly increases intracellular TauT, with greater response than pure Betaine re
  • 42. Clinical Studies Effect on Organic Osmolyte Transporter EVALUATION OF OSMOLYTE TRANSPORTER r X y Betaine 20pM Nuclei and TauT Hydrosella™ 0.4% Nuclei and TauT TauT expression in green Untreated I Nuclei and TauT Hydrosella™ significantly increases osmolyte transporter, helping the skin natural osmolyte defense system -------—--------- -- • ■-------- Protocol • Human skin explant from a 43 and 44 years old Caucasian female • Application of Hydrosella™ at 0.4% or Betaine at 5 or 20pM for 48h • Betaine content of Hydrosella™at 0.4% is ± 5pM • Evaluation of organic osmolytes transporter content by immunostaining (green labelling) r. Protocol • Human skin explant from a 43 and 44 years old Caucasian female • Application of Hydrosella™ at 0.4% or Betaine at 5 or 20|iM for 48h • Betaine content of Hydrosella™at 0.4% is ± 5pM • Evaluation of organic osmolytes transporter content by immunostaining (green labelling) TO
  • 43. Clinical Studies Effect on Cell Total Volume Recovery EVALUATION OF CELL VOLUME RECOVERY EVALUATION OF TOTAL CELL VOLUME RECOVERY (%) Protocol • Normal human epidermal keratinocytes (NHEKs) from 3 different donors • NHEKs were seeded at single cell density and exposed to 5 minutes in isoosmotic conditions, 15 minutes hyperosmotic conditions and 15 minutes in isoosmotic conditions, in absence (control) or presence of Hydrosella™ 0.2% • NHEKS were treated with Calcein green for visualizationby live cell imaging Protocol • Normal human epidermal keratinocytes (NHEKs) from 3 different donors • NHEKs were seeded at single cell density and exposed to 5 minutes in isoosmotic conditions, 15 minutes hyperosmotic conditions and 15 minutes in isoosmotic conditions, in absence (control) or presence of Hydrosella™ 0.2% • NHEKS were treated with Calcein green for visualizationby live cell imaging f> Hydrosella™ improves keratinocytes volume recovery I_______________________________________________________________________________________=______________________> 0 Untreated 0 Hydrosella'" 0.2% Test made at The of Manchester
  • 44. Clinical Studies Preventive Effect on Neutral Lipids 0 Untreated DO £ Defipidated Q Dellpidated+ Hydrosella'" 1% Neutral lipid expression ir Protocol • Human skin explant from a 34 years old Caucasian female • Explants were incubated with Hydrosella™1% or without (control) • Hydrosella™was appliedon skin explants on DO, D2 and D3 before delipidation • Delipidation made with ether/acetone solution (1:1) • Evaluation by lipid staining with LipidTox™ green neutral lipid at DO, D3 and Db EVALUATION OF PREVENTIVE EFFECT OF HYDROSELLA1" ON LIPID CONTENT z Hydrosella™ provides a preventive action for skin lipid X ____________ protection and increases its production J 16
  • 45. Clinical Studies Curative Effect on Neutral Lipids 0 Untreated DO 0 Delipidated f Delipidated * Hydrosella"-1% Neutral lipids expression in green Protocol 120- § o - Q = 5 c * 5 ? • Human skin explant from a 34 years old Caucasian female • Pre-cultures for 3 days, then delipidated with ether/acetone solution (1:1) • Hydrosella™ 1% was applied or not (control) once on skin explants • Evaluation by lipid staining with LipidTox™ green neutral lipid (T3h, DI, D2) [3 DAYS PRE- CULTURE DO D0*3H DI D2 1 1 1 ••• • • | (------------------------------------------------------------------------------------------------------------------------------------- Hydrosella™ increases skin lipid production following dehydration to prevent further water loss
  • 46. Clinical Studies Effect on Stratum Corneum Thickness Protocol • Human skin explant from a 34 years old Caucasian female • Pre-cultures for 3 days, then delipidated with ether/acetone solution (1:1) • Hydrosella™ 1% was applied or not (control) once on skin explants • Evaluation by microscopical observation at T3h, DI and D2 EVALUATION OF STRATUM COONCUM THICKNESS FOLLOWING DEUPIDATION [ 3 DAYS PRE- CULTURE DO DO*3H DI D2 ] rz ••• *± * • J Deapdatton f Eiplants sanping f FWOud appteabor , ___________________________•p <0.05," p <001, — p <0.001 • Untreated f Centro! Q Hyttoselia" 1% Hydrosella™ enhances the stratum corneum thickness to maintain a well-hydrated skin
  • 47. Clinical Studies Evaluation of Skin Water Content Protocol • 10 female volunteers with normal to dry skin • 1 application on forearm of Hydrosella™1% • Evaluation of skin moisturizing by Corneometer • Placebo f Hydrosella ' 1% f-----------------------------------------------------------------------------------------------------------X Hydrosella™ rapidly increases skin moisture content with a continuous effect up to 72hrs after single application < ■ ■ - - > INGREDIENTS INCI NAMES ACTIVE FORMULA (%) PLACEBO (%) Dciornzed Water Water 97.00 97.40 Glycerin Glycerin 060 120 Carbopol ultrez 21 Acrylates/C10-30Alkyl Acrylate 050 050 Crosspolymer Chiorphenesin Chiorphenesin 0.30 0.30 Phenoxyethanol Phenoxyethanol 0.60 060 Hydrosella'" Glycerin(and) Water (and) 1.00 000 Erythrito1 (and) Hibiscus Sabda’if'a Fruit Extract — EVALUATION OF SKIN HYDRATION AFTER SINGLE APPucATioua^k. Tlh T24h T4Sti T72h "D<001.“p<0001 19
  • 48. Clinical Studies Evaluation of Skin Water Loss Protocol • 10 female volunteers with normal to dry skin • 1 application on forearm of Hydrosella™1% • Evaluation of skin water loss by TEWL Tlh T24h T48h T72h ______________________“*p<0001 > • Placebo Q Hydrosella' 1% f INGREDIENTS INCI NAMES ACTIVE FORMULA (%) PLACEBO | (%) Deionized Water Water 97.00 97.40 Glycerin Glycerin 060 120 Cart spot ultre2 21 Acrylates/C1O-3OAlkyl Acrylate Crosspolymer 0.50 0 50 Chlorohenesm CNorphenesm 0.30 0.30 Phenoxyethanol Pbencxyetoanol 0.60 0.60 Hydrosella- Glycerin(and) Water (and) Erythritol (and) Hibiscus SabdariffaFruit Extract 1.00 000 (---------------------------------------------------------------------------------------------- Hydrosella™ rapidly decreases skin water loss with a continuous effect up to 72hrs after single application
  • 49. Novel approach in Dry skin disorder that targets Inter-cellular Moisturization Hydrosella™ is standardized in betaine, a natural organic osmolyte Helps to increases production of tight junction protein Occludin ,thereby reduces Trans Epidermal Water Loss(TEWL) Increases production of Tight Junction Protein Occludin2 Reduces TEWL 21
  • 50. Clinical Studies Curative effect on Occludin Production CURATIVE EFFECT ON OCCLUDIN PRODUCTION Protocol • Human skin explant from a 34 years old Caucasian female • Pre-cultures for 3 days, then dellpidated wrth ether/acetone solution (1:1) • Hydrosella"* 1* was applied or not (control) once on skin explants • Evaluation by immunostaining and microscopical observation 3 hours after delipidation T>HConqpl ’ T3h ’-HydrcneU*’’ • 1% Hydrosella’" increases tight junction proteins expression (occludin) to restore and to improve skin barrier function 02
  • 51. Novel approach in Dry skin disorder that targets Inter-cellular Moisturization Replenish the Lost Ceramides Significance of Ceramides Compared to dry and normal skin, ceramide I, II, III, IV, V and VI diminish with dryness, while CERs are at a high level in normal skin Forming intercellular lipid lamellar structures is an important factor for the formation of an effective barrier to reduce TEWL.
  • 52. Scientific Article “CERs are the main lipids in the stratum corneum, which play a key role on the barrier function" “Compared to dry and normal skin, ceramide I, II, III, IV, V and VI diminish with dryness, while CERs are at a high level in normal skin". cosmetics IMDPIJ Review Recent Advances on Topical Application of Ceramides to Restore Barrier Function of Skin Emine Kahraman, Melis Kavkin, Hurnevra Sahin Beklav and Scvgi Gungor' Department <>f Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University. 34116 Beyazit, Turkey • Correspondence sgungorihstanbuledu.tr chKk lor Received: 3U |une 21H9; Accepted: 17 August 2019; Published: 20 August 2019 l»4«t»l Abstract: Human skin is the largest organ of the body and is an effective physical barrier keeping it from environmental conditions. This barrier function of the skin is based on stratum corneum, located in the uppermost skin. Stratum ameum has corneocytes surrounded by multilamellar lipid membranes which an1 composed of cholesterol, frw fatty acids and ceramides (CFRsl Alterations in ceramide content of the stratum ameum are associated with numerous skin disorders. In recent years, CERs have been incorporated into conventional and novel carrier systems with the purpose of exogenously applying CERs to help the barrier function of the skin. This rev iew provides an overview of the structure, function and importance of CERs to restore the barrier function of tire skin following their topical application. Keywords: skin barrier; skin disorders; ceramides; topical application 1. Skin Barrier Human skin is the largest organ of the body, accounting tor 16% of total weight and having an area of 1.8 m*. It prevents excessive water loss from the body and helps to maintain electrolyte balance and involves some metabolic processes that are related to immune system. It also protects the organism against microorganisms, ultraviolet radiation, toxic substances and mechanical damage, creating a physical barrier between environmental conditions and the body. Basically, the human skin is a multi- layered membrane From deep to superficial these layers are (Figure 1) |lf Cosmetics 2019, 6, 52; doi:10.3390/cosmetics6030052.
  • 53. Novel approach in Dry skin disorder that targets Regulation of Moisturization Importance of Hyaluronic Acid (PrincipHyal 800-1000) HA - a biologic humectant, can penetrate into the stratum corneum if it is of the correct size Topical HA suitable for all Fitzpatrick skin types Moisturizing and anti-ageing effects which help in skin regeneration and smooths the skin Draelos ZD, Diaz I, Namkoong J, Wu J, Boyd T. Efficacy Evaluation of a Topical Hyaluronic Acid Serum in Facial Photoaging. Dermatol Ther (Heidelb). 2021 Aug;11(4):1385-1394. doi: 10.1007/s13555-021- 00566-0. Epub 2021 Jun 26. PMID: 34176098; PMCID: PMC8322246. . Juncan AM, Moisa DG, Santini A, Morgovan C, Rus LL, Vonica-Tincu AL, Loghin F. Advantages of Hyaluronic Acid and Its Combination with Other BioactiveIngredients in Cosmeceuticals. Molecules. 2021 Jul 22;26(15):4429. doi: 10.3390/molecules26154429. PMID: 34361586; PMCID: PMC8347214
  • 54. Novel approach in Dry skin disorder that targets Regulation of Moisturization Reduces TEWL Maintains skin hydration Skin protection by forming viscoelastic film Importance of Hyaluronic Acid (PrincipHyal 800-1000) Cuticle PRODUCT CLASSIFICATION FUNCTIONS AmviHyaP* 800-1000 kDa Medium molecular weight-HA (MMW-HA) • Maintains skin hydration • Softens the Skin Draelos ZD, Diaz I, Namkoong J, Wu J, Boyd T. Efficacy Evaluationof a Topical Hyaluronic Acid Serum in Facial Photoaging. Dermatol Ther (Heidelb). 2021 Aug;11(4):1385-1394. doi: 10.1007/s13555-021- 00566-0. Epub 2021 Jun 26. PMID: 34176098; PMCID: PMC8322246. . Juncan AM, Moisa DG, Santini A, Morgovan C, Rus LL, Vonica-TincuAL, Loghin F. Advantages of Hyaluronic Acid and Its Combinationwith Other BioactiveIngredients in Cosmeceuticals. Molecules. 2021 Jul 22;26(15):4429. doi: 10.3390/molecules26154429. PMID: 34361586; PMCID: PMC8347214
  • 55. Take home message:  Till date choosing, the right moisturizer is still a matter of trial and error.  Numerous cosmetics are being released by a variety of cosmetic companies today, and in particular, moisturizers are used not only for patients suffering from skin diseases but also for people with normal skin.  The key to future moisturizer therapy will be to tailor specific agents to specific dermatological needs.  Knowing the in and out of the actives and their interactions with the skin will help better usage and efficacy of the available moisturizers.

Editor's Notes

  1. Moisturisers bridge the gap between medicine and consumer goods
  2. Moisturisers bridge the gap between medicine and consumer goods
  3. Corneocytes are filled with natural moisturising factor, a collection of natural humectants which maintain skin hydration The constituents of NMF are derived from profilaggrin, a structural component of the CE expressed during keratinocytes differentiation. NMF is important for maintaining an acid environment at the outer surface of the SC In order to balance the introduction of new cells in the basal layer of the epidermis, mature corneocytes are shed from the surface of the SC is a process referred to as desquamation. Desquamation involves the degradation of the extracellular corneodesmosomes by a cocktail of proteases regulated by protease inhibitors. The optimum pH for serine protease activity is slightly alkaline in contrast to the normal acidic pH of the skin.
  4. Skin becomes dehydrated when the stratum corneum is unable to retain water and loses moisture faster than it is replenished. Xerosis refer to the concept of dry skin; severe xerosis can lead to the onset of a type of eczema characterized by intensely itchy, fissured, and cracked skin called xerotic eczema or eczema craquele. The epidermis is the skin layer that is most affected by Xerosis. [Figure 1] Dry skin affects the patient’s quality of life, and severe xerosis can interfere with work productivity, especially when the hands are affected. Barrier dysfunction results in an increase in transepidermal water loss (TEWL). Reduced blood flow, reduced stratum corneum hydration and elevated skin pH, decreased enzyme activity, an altered cytokine profile and changes in the properties of epidermal stem cells contribute to impaired reconstitution. Elevated TEWL is a marker of the disrupted skin barrier in inflammatory skin diseases.
  5. Topical preparations for the treatment of dry skin should contain molecules that activate the epidermal regeneration process and restore the lipid content of the horny layer.   Lipids are the essential ingredient in formulations used to treat dry skin. The delivery of water alone will not repair the lipid barrier, natural physiologic lipids (cholesterol, ceramides, and fatty acids) must also be supplied. The principal lipid components found in the epidermis are ceramides and cholesterol derivatives. Physiologic lipids, such as the ceramides, function as structural elements in the epidermal barrier and mediate the stimuli that trigger epidermal repair.   With decreasing ceramide levels in the skin, the barrier function of lipid envelopes becomes incapacitated. Compared to dry and normal skin, ceramide I, II, III, IV, V and VI diminish with dryness. Ceramides Facilitate epidermal differentiation by re-establishing the cellular lipids. Cholesterol Ensures the availability of this natural lipid in the stratum corneum to facilitate regeneration and epidermal differentiation.   Hydrating agents play an active role in the process of maintaining the water balance of the stratum corneum. Hyaluronic acid Creates a barrier layer, it has High capacity to hydrate the stratum corneum Hyaluronic acid Restores the flexibility and elasticity of the skin and is well tolerated by skin.     Humectants are natural oily substances that do not intervene in the metabolic processes of the skin but rather act passively by preventing excessive water loss.   There are significant changes in lipids in skin disease. Common and rare skin conditions alike are linked to alterations in skin lipid composition and metabolism including atopic dermatitis, psoriasis, acne vulgaris, lamellar ichthyosis, recessive X-linked ichthyosis, bullous ichthyosiform erythroderma, type 2 Gaucher disease, Sjorgen-Larsson syndrome, essential free fatty acid deficiency, aged dry skin, and hypohidrotic ectodermal dysplasia.   Common trends across different skin diseases are notable, e.g. decreases in fatty acid chain length in diseased skin, or decreases in total ceramide concentrations. Barrier function and skin hydration depend on the different types of lipids present in the stratum corneum and the levels of both lipids and natural moisturizing factor.   A lipid deficit destabilizes stratum corneum hydration, affecting the elasticity and flexibility of healthy skin. The intercellular lipid component is arranged in bilayers between the corneocytes. These lipids, which are formed in the lamellar or Odland bodies of the stratum granulosum, migrate upwards into the stratum corneum during the process of epidermal differentiation.   The lipids secreted are the substrate of the enzymes—also present in the lamellar bodies—that transform the glucosphingolipids into a mixture of nonpolar lipids, including ceramides, free sterols, essential and nonessential free fatty acids, and cholesterol . Ceramides are the principal source of essential fatty acids. Linoleic acid, a structural element that plays a key role in epidermal barrier function, is the most important of these fatty acids.   Xerosis or dry skin is a common skin disorder and is characterized clinically by rough, scaly, and often itchy skin. It is characterized pathophysiologically by a disrupted stratum corneum, dehydration, and impaired keratinocyte differentiation. Treatment of xerosis should seek to restore physiologic lipids in the epidermis and provide substances that facilitate epidermal differentiation and restoration of skin barrier function.
  6. Classically, moisturizers have been classified into emollients, occlusives and humectants.(Figure 2)However, recently several newer agents have become available, designed specifically in an attempt to repair the defective barrier in AD