Download Innovation in Skin, Hair, and Nails Zoe Diana Draelos, MD zdraelos

Innovation in
Skin, Hair, and Nails
Zoe Diana Draelos, MD
[email protected]
Innovation in Aging and Skin Care
+How is longevity related to the immune inflammatory response that causes cutaneous
aging?
+What are growth factor containing cosmeceuticals?
❖ Are cosmetics dangerous?
❖ Do probiotics have a role in skin care?
Why do humans live so long?
•:•Humans began living longer when they became meat eaters about 3.4-2.5 million
years ago
•:•Humans began hunting game 1.8 million years ago, abundant calories and proteins for
brain growth
•:•Uncooked meat exposed humans to many pathogens since all part of carcass
consumed
•:• Cooking emerged 1 million years ago
Human vs. Chimpanzee Longevity
•:•Humans and chimpanzee genomes are 99% identical
❖ The uniquely human 1% possesses a high number of genes important in host defense
and immunity
❖ These genes were in the inflammatory response
❖ Natural selection endowed humans with a superior immune system for fighting off
microbial threats from meat ingestion extending human life span
The Inflammatory Response
•:•Humans have a unique apolipoprotein E (APOE) gene important in the transport and
metabolism of lipids different from chimps
•:•APOE e4 ramps up in the acute phase of inflammation increasing IL6 and inducing
fever and fighting off microbe replication
•:•Humans with APOE e4, which facilitated the intestinal absorption of lipids and the
efficient storage of fat in body tissue, lived longer
Antagonisitic Pleiotropy and Longevity
❖ APOE e4 allowed humans to survive to the age of reproduction, but increased disease
in old age (antagonistic pleiotropy)
+Increased lipids cause heart attacks, strokes
•:•200,000 years ago H. sapiens emerged from Africa and APOE e3 allele appeared
slowed aging
❖ APOE e3 allele found in 60-90% of humans
APOE e3 and Human Aging
•:•Enhanced health among 40-70 year olds
❖ New gene had less inflammatory response
❖ Better adapted to meat and fat rich diets
%%Lower serum cholesterol, lower incidence of coronary artery disease, decreased
cognitive decline
❖ APOE e3 live on average 6 years longer than APOE e4 carriers
What are Growth Factor Cosmeceuticals?
❖ GF are multifunctional peptides active in the picogram range
•:*GF names have more to do with the circumstances in which they were identified rather
their effect
•:*GF are defined as factors intended to "mobilize, stimulate, decrease, or otherwise alter
the production of cells in vivo."
•:*GF act as signaling molecules between cells by binding to cell surface receptors
Growth Factor (GF) Targets
•:*GF modes of targeting:
—GF release into the blood stream to reach distant targets (endocrine mode)
—GF diffuse over short distances to affect other cells (juxtacrine mode)
—GF influence neighboring cells (paracrine)
—GF act on the cells in which they are produced (autocrine mode)
•:•Dermatologic relevant GF: epidermal growth factor, keratinocyte growth factor,
fibroblast growth factor, and platelet-derived growth factor
Epidermal Growth Factor (EGF)
•:•EGF binds to specific high-affinity, low-capacity receptors on the surface of
responsive cells
•:•Intrinsic to the EGF receptor is tyrosine kinase activity
•:•EGF has proliferative effects on cells of both mesodermal and ectodermal origin,
particularly keratinocytes and fibroblasts
•:•Growth-related responses to EGF include the induction of nuclear proto-oncogene
expression, such as FOS, JUN and MYC
Epidermal Growth Factor Effects
❖ Produced from macrophages and monocytes
❖ Effects epithelium and endothelial cells
❖ Stimulates proliferation of keratinocytes, fibroblasts, and endothelial cells
. .
***Stimulates keratinocyte migration
•••• Clinical trials ongoing for venous ulcers
❖ Increased EGF seen in cancers, cetuximab inhibits ECF in colon cancer
Keratinocyte Growth Factor (KGF)
❖ KGF also known as FGF7 (Fibroblast Growth Factor 7)
+ Found in the epithelialization-phase of wound healing
❖ KGF is a small signaling molecule that binds to fibroblast growth factor receptor 2b
❖ KGF-1 contributes to the growth of breast cancer (Journal of NCI, 98:12, 2006)
Fibroblast Growth Factor (FGF)
•:•FGF is a very potent angiogenic factor
+Derived from monocytes, macrophages, endothelial cells (22 human FGFs identified)
❖ Targets endothelium, fibroblasts, keratinocytes
•:•Induces proliferation of endothelial cells, keratinocytes, fibroblasts, chemotaxis, ECM
•:* Clinical trials ongoing for diabetic, venous, pressure ulcers
Platelet-Derived Growth Factor (PDGF)
❖ PDGF produced by platelets, macrophages, neutrophils, smooth muscle cells
••••PDGF targets fibroblasts and smooth muscle cells
••••Induces proliferation of smooth muscle cells and fibroblasts, chemotaxis, ECM,
muscle contraction
❖ Clinical trials for diabetic, pressure ulcers
•
Platelet-Derived Growth Factor Effects Are Growth Factors Safe?
•:•Growth factors are found in human fibroblast conditioned media, a "biologic"
substance
•:•Biologics must file a Biologics License Application (BLA) to obtain FDA approval
and are regulated like Rx drugs with required studies and labeling requirements
•:* Growth factors may be an arena where cosmeceuticals meet pharmaceuticals
depending on derivation of active agent
Growth Factor Contamination
•••• Growth factors may be derived from human tissue, such as human foreskins
• The human derived tissues may be contaminated with HIV, Hep C, Hep B, HPV, HSV
❖ Human recombinant growth factor now available
•:*At present no standards exist for quality control on cosmetic growth factor products
because they are not regulated
Growth Factors: Drugs or Cosmetics?
•:•Human fibroblast conditioned media defined as "a physiologically balanced, naturally
secreted and stabilized combination of multiple natural messenger proteins" in
cosmetic website
•:•Effects characterized as "incorporating the science of the skin's own healing abilities,
utilizing restorative ingredients that work below the skin's surface to rejuvenate skin
and counteract the effects of time on the skin"
Growth Factor Manufacture
+ Need source of fibroblasts: human infant foreskin or neonatal cell bank
❖ Cells cultured either in petri dish or on dextran microbeads
•:•Fibroblasts remove nutrients from media and release by-products, which could contain
110 different materials
•:•One proprietary culture method places fibroblasts under low oxygen tension (5%) to
"allow the cells to revert back to an embryonic-like state and exhibit stem cell
properties"
Do Growth Factor Cosmetics Work?
•:•GF are very large proteins (EGF has 53 amino acid residues, 3 disulfide bonds)
•:• Very large proteins do not penetrate the skin
+ The stratum corneum is very good at blocking proteins because they are the major
allergens in the environment providing a survival benefit
•:*GF must be penetration enhanced and carefully formulated to provide effect
(nanoliposome encapsulation)
Dangerous Ingredients: Preservatives # Formulations 36,811
•:• Methylparaben: 13,434
•:•Propylparaben: 10,421
•:* Phenoxyethanol: 8,878
•:•Butylparaben: 5,289
•:•Ethylparaben: 4,869
+Isobutylparaben: 2,639
•:•Methylisothiazolinone: 2,408
Parabens
•:•Parabens are preservatives commercialized in the 1950s (antifungal, antibacterial)
+ Family: methylparaben, ethylparaben, propylparaben, butylparaben, isobutylparaben
+ 90% of grocery items contain parabens
•:• Found in deodorants, toothpaste, shampoo, conditioner, makeup, body lotion,
everything
Paraben Concerns
•:•Parabens mimic estrogen by binding to estrogen receptors
•••• Possible increase in breast cancer? Lower age of puberty?
•:•Found in breast cancer tumors (20ng/gm)
•••• EU limits concentration of propylparaben and butylparaben from 0.4% to 0.14%,
banned from diaper products in April 2015
Paraben Safety
❖ Naturally occurring methylparaben in blueberries, acts as antimicrobial
❖ Butylparaben is 10,000 times weaker than estradiol
❖ Estrogenic effect was only seen at a dose 25,000 higher than preservative level
❖ Parabens are currently accepted to be safe at preservative levels
Dangerous Ingredients: Phthalates
•:•Phthalates are plasticizers
+Increase plastic flexibility, transparency, durability, and longevity
•:•Also fix or hold color and fragrance
•:•Used to soften polyvinyl chloride (PVC)
•:•Removed by heating or solvents
•:•Found in milk, butter, meats
•:•Most Americans have multiple phthalates in their urine (www.cdc.gov )
Phthalate Concerns
❖ Phthalates are physically not chemically bound and can be easily released into the
environment, major air pollutant
❖ Phthalates have been banned in toys
•:• Phthalates are released from flooring, plastic containers, medical devices, gloves, IV
tubing, erasers, pill coatings
❖ Cosmetics: moisturizers, skin softeners, penetration enhancers, anti-cracking agents in
nail polish, anti-foaming agents in aerosols
Phthalate Safety
•:•Rodents show altered hormones and birth defects
•;• Cause of breast cancer? Obesity? Insulin resistance? Hormone disruptor? ADHD?
•:• Can be absorbed through the skin in leave on products
•:•FDA stated phthalates are not harmful to consumers as cosmetic products are currently
used, but continues to monitor products especially baby care products
Are topical probiotics useful for skin health?
+Identified in 1908 by Eli Metchnikoff
+ Noted Bulgarian peasants longevity due to consumption of fermented milk products
❖ Probiotic term coined in 1965 (Lilly and Stillwell): a substance secreted by one
organism that stimulates the growth of another
+ Redefined by Marteau 2002: microbial preparation with beneficial effect on health and
well being
Topical Probiotics and Skin
•:•Lactobacillus (LB) produces bacterocins (type of antimicrobial peptide) inhibiting
gram (-) and (+) organisms; may be anti-inflammatory
+ Topical LB o/w cream decreased Balsam of Peru allergy induced erythema, reduced
acne lesion size and erythema in 10 subjects
+ Interesting finding, but cannot draw conclusion due to small sample size and lack of
control
Innovation in Hair Care
❖ what characterizes hair photodamage?
•:•what are the new developments in hair dye chemistry and fashion?
❖ Is it possible to moisturize hair?
• How can hair loss due to hair breakage be ameliorated?
Photodamaged Hair
❖ Hair is damaged by UV exposure
❖ Oxymelanin is produced in the hair shaft by UVA and hair keratin degraded
':'Results in yellowing of blonde hair, red hues in brunette hair
❖ UV weakens the hair structurally resulting in hair breakage and loss
Photodamaged Hair
+Some conditioners and hair sprays contain a sunscreen, no claims can be made
••••Must be reapplied with each shampoo
❖ Best protection is still a hat or umbrella
❖ UV damaged hair is frizzy, easy fractured, does not hold dyed color
❖ Tanned skin usually means UV exposed hair
Hair Color and Photoprotection
❖ Pigment is best photoprotection for hair, either natural or dyed
••••Gray hair is most susceptible to photodamage, followed by blonde hair
❖ Hair dye chemistry requires melanin for optimal oxidation/reduction reaction
Natural Hair Color
❖ Melanin is a polymer of indole-5,6-quinone
❖ Production of melanin results in the formation of radicals and toxic by-products that
accumulate in melanocyte with time
• Decreased melanin production or graying occurs with this accumulation
❖ Most common reason to dye hair is to cover gray in both men and women
Types of Hair Dyes
••••Progressive
••••Temporary
•
***Semi-Permanent
•
***Permanent
— Dyeing
—Bleaching
—Streaking
Progressive or Metallic Dyes
+ Most commonly use lead (1%), but not in bioavailable toxic form
+ Metallic salts binds to sulfur in hair keratin to produce metal sulfide
+ Damage hair shaft producing brittleness
+ Cannot combine with permanent waves, causes hair shaft rupture
❖ Produce gradual darkening, but poor color
+ Only shampoo once weekly during color induction
Temporary Hair Dyes
•:•Applied as a film over the hair shaft
':'No damage to hair shaft occurs
•:•Use acidic dyestuffs under acidic conditions to allow dyestuff to coat hair
•:• Removed in one shampooing
•:•Popular for party colors
Semi-Permanent Hair Dyes
':'Last from 6-10 shampoos
•••• Small molecules that minimally penetrate the hair shaft during 20-30 minute contact
•:•Wash out some color with each shampooing
•:• Dyes from chromophoric nitro group
❖ Blue creates brown on pigmented untreated hair, but makes treated hair appear blue
due to increased porosity and penetration
Permanent Hair Dyes
•••• Chemical reaction creates pigmented molecules within the hair shaft
•:•Alkaline solution (pH 8.5-10) with dye precursors and couplers mixed with hydrogen
peroxide
•:•Hydrogen peroxide can damage natural melanin pigments lightening hair
Hair Bleaching
•:• Hair color is lightened due to removal of melanin pigments, known as bleaching
•:•Eumelanin easier to remove than pheomelanin, bleached hair turns red
....Peroxide very damaging to hair shaft, more peroxide volumes lightens hair more
':• Tremendous cuticle disruption, excessive hair breakage noted
Hair Streaking or Foiling
•:• Method of selecting specific hair strands to dye different colors
•:•Hair strands are isolated with aluminum foil
+Lighter hair strands will break before darker hair strands
❖ Photodamage more prominent in lighter strands over darker strands, turn yellow
Newest Hair Dye Development: Non-Ammonia Hair Dye
❖ Contains MEA in an oily delivery system without water
+ Lipids provide protection
❖ Developer with cationic polymers mixed with color mixed with oily gel
❖ Less damaging oxidative dye
Hair Moisturization and Lipids
❖ Hair health is in part related to the covalently bound monomolecular layer of a
branched fatty acid: 18-methyl eicosanoic acid (18-MEA)
❖ Layer is intensely hydrophobic, preventing water access to hair with wetting
%%Wet hair possesses decreased physical properties
Chemical Trauma: Lipid Damage
%.•18-MEA removed with chemical hair processing, cannot be replaced due to oxidation
of the binding sites on the shaft
❖ Can only be partially temporarily replaced with conditioners
❖ Biggest hair health challenge for industry
Replacing the Lipid Film
❖ Argan oil and Moroccan oil high in essential fatty acids (linolenic, linoleic acid)
❖ Essential fatty acids are closest to 18-MEA, but must be replaced with each
shampooing
+Dimethicone also popular to create film
%.• Sulphate free shampoos remove less sebum due to less detergency, popular trend
Improving Damaged Hair
•:* There is amino acid loss in damaged hair
•:* Sulfur containing amino acids are preferentially lost, disulfide bonds necessary for hair
structural strength and resistance to breakage
❖ Protein containing hair care products attempt to replace lost amino acids
Summary: Hair Care Innovation
•:•Hair photodamage can be prevented by sunscreen-containing products, but no
photoprotection claims can be made
+ Hair dye provides photoprotection, but also damages structural hair integrity
•:•Hair lipids necessary for hair health, but binding sites are not available for
reattachment
•:•Hair breakage is related to loss of sulfur based amino acids, but cannot be replaced
Nail Polish Innovations
+Photochromic nail polish
+Photothermic nail polish
•:•Caviar nail polish
❖ Magnetic nail polish
❖ Crackle nail polish
+Breathable nail polish
UV Color Changing Nail Polish
❖ Based on an organic molecule that can exist in one of two configurations
❖ Molecular classes: spiropyrans, spirooxazines, diarylethenes
•:. UV breaks the carbon-oxygen Spiro bond allowing the molecule to exhibit color when
the absorption spectrum shifts to lower energy and into the visible range
•:. Removal of UV allows the molecule to rearrange to the more stable colorless state
❖ Rearrangement is faster at higher temperatures
Thermochromic Nail Polish
•:•Nail polish changes color in response to surrounding temperature
•:• Temperature below solvent melting point causes hydrogen donation interaction
between molecules, leading to rearrangement and the colored state
•:•The solvent melts with increasing temperature, molecular interaction stops, colorless
state reappears
Caviar Nail Polish
•:•Caviar microbeads are made of glass or plastic
•:•Nail polish applied to nail and microbeads are poured over wet polish or pushed into
container with microbeads
•:•Nail polish is allowed to dry
•:* Topcoat is applied to seal the beads onto the nail
•:•Different colors and sizes of beads can be combined for various visual effects
Magnetic Nail Polish
•:•Different colored particles orient themselves when a magnetic field is applied to wet
nail polish creating patterns in the magnetic field
+Magnetic particles: nickel, cobalt, iron gadolinium, terbium, erbium
•:•Most common metal is magnetite (iron oxide)
•:•Asymmetric oblong particles create novel shapes and patterns
•:•Different colored nail polishes can be combined for intense pattern variation
Crackle Nail Polish
❖ Apply regular nail polish and allow to thoroughly dry
❖ Apply crackle nail polish on top
❖ Apply a clear coat to prevent chipping
•:•Crackle is created as rapid uneven drying is created by the addition of ethyl alcohol
❖ Thinner films lead to thinner cracks while thicker films lead to thicker cracks
Breathable Nail Polish
•:•Water and oxygen permeable nail polish
•:•Contains a resin similar to one used in contact lenses
•:•Popular with Muslim women who cannot wear nail polish due to wudu-washing in
preparation for prayer, even nails must be washed
❖ Conventional nail polish is not water permeable, breathable nail polish meets wudu
requirements
Innovations in Skin, Hair, and Nails
❖ Many new products have been introduced for skin care: antioxidants, growth factors,
paraben free products, probiotic creams
+ Hair care products are attempting to replace loss lipid and proteins that damage
appearance
❖ Nail cosmetics continue to focus on new ways of coloring and adorning the nail plate