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Getting Under Your Skin
By Sarah Mahoney
May / June 2006
Cutting-edge skin care is now less about ingredients than infiltration--getting the product precisely to where it can do the most good
For years, women have been conditioned to pay close attention to the ingredients in skin-care products. Whether the contents are botanical like elderberry extract, chemical like alpha hydroxy acids, or biological like colostrum, we all want to know: What's in this stuff that makes it work?
But the latest skin-care breakthroughs are less about ingredients than delivery--how to get the key ingredients to penetrate the various skin layers and hit the cells that need them most. The current skin-care mantra is that surface-hugging moisturizers aren't enough. The cells that play the biggest role in keeping skin young, the fibroblasts, are deep down in the mesoderm (middle layer). To be effective, products must be more than skin deep--way more.
The problem is reaching the fibroblasts. Skin is not fragile but admirably tough--more barrier than membrane. That's why the outer (and toughest) layer, the stratum corneum, is also called the horny layer. It's about ten microns thick--that's a lot in the dermatology world--and consists of layers of the same dead cells (corneocytes) that compose fingernails, according to Jagdish Singh, Ph.D., the chairman of the pharmaceutical-science department at North Dakota State University. The horny layer is often compared to a brick-and-mortar construction: The large cells of the epidermis are packed tightly together, while the small spaces between them are filled with fats (lipids). The design is foolproof: The corneocytes keep foreign material out, and the lipids make sure water stays in.
Yet it's on this hard ground that most products are meant to work. "Most skin-care products focus on moisturizing the 'dead' layer of the skin, the 15 or so layers that require water so they don't feel dry," says Mary Begovic Johnson, M.S., a principal scientist in Procter & Gamble's beauty-care division, which markets the top-selling Olay Regenerist line.
While the idea of delivering medicine through the skin (transdermally) is as ancient as the poultice, it took until 1979 to engineer a technology--the patch--that could do it, says Audra Stinchcomb, Ph.D., an associate professor of pharmacy at the University of Kentucky and member of the American Association of Pharmaceutical Scientists. The first patch to hit the market was a prescription-only treatment for motion sickness. It took 15 more years for the FDA to approve a medicine-dispensing patch (containing nicotine) for over-the-counter sale. Currently, there are more than 35 patch products, delivering everything from pain relievers to birth control, says Stinchcomb, who is also the chief scientific officer for AllTranz, a Lexington, Kentucky, company that develops transdermal delivery systems.
Penetrating the skin effectively (meaning therapeutically) is largely a matter of molecule size and transport mechanism. "The size of the molecule definitely affects how well it penetrates," says Stinchcomb, "and transdermal drugs currently available all use molecules that usually have a molecular weight less than 500 dalton, with 1,000 being the maximum." (One dalton is the weight of a hydrogen molecule. At only 162 dalton, nicotine slips easily through the skin, whereas insulin, at 6,000 dalton, can't penetrate at all.)
But ingredients needn't be nano-size (a billionth of a meter wide) to penetrate the skin. Some larger molecules can also penetrate, either because of their makeup or where they're programmed to go, for instance, through the oil glands. Absorption is also affected by whether a molecule is positively or negatively charged, and whether it's water or lipid based.
While the innovation spotlight often falls on molecule size, it's really the means of ferrying it into the skin that enables even the tiniest peptide (see "Absorption Glossary" on page 100) to get to work. Most new delivery systems bind the key ingredient to a lipid because they easily go around skin cells. Scientists call it traversing the intercellular matrix. It's easier to grasp if you imagine the product going through the mortar rather than the bricks.
Traversing the intercellular matrix is just one route into the skin, though. In fact, there are now so many methods that it's difficult to categorize them. Some ingredients travel through pores or sweat glands. Some make microscopic holes in the top skin layer by removing lipids; others mimic human cells, allowing them to exchange material across membranes.
"Delivery systems are it, in a nutshell," says Susan Weinkle, M.D., a dermatologist in Bradenton, Florida, and past president of the Women's Dermatologic Society. "Consumers are catching on to the idea that if an active ingredient can't penetrate into the skin, what good is it? Take collagen, for example. For years, companies touted collagen-rich products, saying that applying collagen would somehow stimulate more production of your own collagen, deep in the dermis. But collagen is such a big molecule it can't penetrate the skin's outer layer. And now that that's been shown through studies, we're seeing a lot less hype about collagen."
From Pharmaceutical to CosmeceuticalMany penetration technologies started in pharmaceutical research, where they led to impressive results. Take retinoids, for instance. Applied topically, they can be very effective at reducing the appearance of wrinkles but also very irritating. Once companies learned how to encapsulate them, says Marianne O'Donoghue, M.D., an associate professor of dermatology at Rush Medical Center in Chicago, that allowed for a gradual release, making them safer for more people, and stronger formulations, making them more effective.
Encapsulation proved to be no less powerful for cosmetics. "With our Future Perfect line, for example, we found that just by encapsulating certain ingredients, we were able to increase its effectiveness by 30 percent," says Daniel Maes, Ph.D., vice president of global research and development at the Estée Lauder Laboratories. So it's no surprise, he says, that Lauder, the parent of such brands as Clinique, Prescriptives, and Aveda, now spends between 10 and 15 percent of its research budget on delivery systems, compared to 5 percent just five years ago.
One of the most successful products using new delivery technology came from what might seem like left field, the study of wound healing at the National Institutes of Health. "Researchers working on wound healing found that five protein fragments [amino acids] would come together to form a pentapeptide," says Procter & Gamble's Begovic Johnson. "When they bound that to a fatty acid, it enabled the molecule to actually penetrate the dead layers, stimulating the production of collagen in the dermis." (See "A Pentapeptide's Progress," opposite.) Procter & Gamble pounced on the technology, and in 2003 it launched the Regenerist line, backing it up with double-blind studies demonstrating significant skin improvement after four to eight weeks of use.
Nano a NanoNo delivery method has generated the skin-care buzz that nanotechnology has. L'Oreal's Revitalift uses it, and the company is said to hold more nanotechnology patents than any other corporation except Hitachi and NEC, an international high-tech services and goods company. (L'Oreal declined to comment for this article.)
"We're learning that just by changing the size of things, you can make the same old chemicals and technologies more effective," says Kevin Ausman, the executive director of the Center for Biological and Environmental Nanotechnology at Rice University in Houston. One example is sunscreen. Nano-engineering zinc and titanium particles makes sunscreen go on smoother, feel silkier, and be transparent, "so you don't look like a lifeguard," says Ausman. That may make consumers actually apply the recommended one ounce every two hours.
Bionova, based in Forest Hills, New York, has used the new technology to deliver old-standby ingredients, namely vitamins A, C, and E, more effectively. Dermatologists have long known that these antioxidants are beneficial to the skin. The trouble is that they're unstable. "While ascorbic acid [vitamin C] in its dry form is stable, as soon as it gets wet, it starts to disintegrate," says Alexander Sepper, Ph.D., M.D., who has degrees in both oncology and dermatology and is the vice president of R&D for Bionova. "And its potency is gone within three or four days after bottling." (Dermatologists have long warned consumers that many products touting vitamin C or E are completely inactive before they even hit the shelves.)
So Bionova set out to make a substance it christened NuCell-Direct, which mimics the cell membrane, giving it the ability to deliver both water- and lipid-soluble ingredients and maintaining the active ingredients' potency much longer. "Now when we measure the activity of the ascorbic acid in our products 90 days after we manufacture them," says Dr. Sepper, "it's still 100 percent active. And after nine months, it has only degraded to 97.8 percent."
But that doesn't mean such teeny-tiny particles don't pose big risks. The Woodrow Wilson Center's Project on Emerging Nanotechnologies has found that little is being spent to explore possible links between exposure to nanomaterials and diseases of the lungs, heart, and skin. A major question, says Andrew Maynard, Ph.D., the center's chief science adviser, is whether nanoparticles may go beyond the skin's deeper levels and into the blood. Right now, the data is inconclusive for both types of nanoparticles, the "hard" ones used in sunscreens and the "soft" nanosomes used in other cosmetics, says Maynard. "So far, it looks as if in healthy skin, they can't. But the bigger question needs to be addressed: Does it matter?" Or, if they do get in, could they do harm?
Many companies jumping on the nano-wagon are busier selling nanotechnology than exploring the possible risks. Others are playing it cool, especially in Europe, where scientific, environmental, and consumer groups have all questioned the safety of nanoparticles in cosmetics. The Royal Society, Britain's equivalent of our Academy of Science, has recommended that the EU require cosmetics companies to make their nanotechnology safety assessments and methodologies public, citing the scarcity of peer-reviewed toxicological data from cosmetics companies.
Other companies are deliberately avoiding nanotechnology, arguing that the skin is designed to be impenetrable for good reason. "We don't use nanotechnology," says Lauder's Maes flatly. "That technology is great for pharmaceuticals but not for cosmetics." What's more, some say, there's no proof that a molecule like collagen will have the same properties once it has been smashed to smithereens. Indeed, scientists at Procter & Gamble have found that once shattered, "not all the molecular fragments of collagen behave like collagen," says Begovic Johnson.
For now, though, the biggest risk nanotechnology poses for cosmetics consumers is probably just getting ripped off. "In the U.S., there's no regulation of nano-labeling," Maynard points out, and it's not as if a consumer can pop a skin cream under a microscope and see if the particles are ten atoms across or less, as promised.
That's also a general concern with products that use advanced delivery systems. Exciting as they are, says Dr. Weinkle, it can be difficult to ascertain which creams and serums are effective and which are just overhyped, overpriced moisturizers. "It's a very perplexing time, because so many of these agents come close to the Food & Drug Administration's definition of a drug, in that they claim to actually change the skin. But these products still aren't evaluated as drugs, so women--who may pay hundreds of dollars for them--don't know if they work or not." Even more confusing, she says, is that what many of these antioxidant-rich products may do best is not so much improve skin as prevent or slow new damage. "But short of creating ten-year studies that do exact matching, it's very difficult to create clinical data that proves it," she adds. The bottom line: Consult your dermatologist before buying.
New Delivery Systems En Route
The next big thing will probably be hexapeptides, predicts Dr. Weinkle, who is also an assistant clinical professor of dermatology at the University of South Florida. "The first tier of skin products improves hydration on the surface of the skin," she says. "The second tier penetrates into the dermis, to boost collagen production, like retinoids and pentapeptides, which have absolutely been proven to help the skin. Scientists hope this new third tier, the hexapeptides, can penetrate past the dermis, where they can slow the muscles' response time. In the face, for instance, that could enhance and prolong the effect of in-office Botox injections."
There is also more research being done on those second-tier products. Somme Institute claims that its Molecular Dispersion Technology 5 (called MDT5 and used in its Somme skin-care line) is a breakthrough because it attaches each of six essential vitamins to a different protein. In addition, Somme claims its products deliver a potent form of vitamin C, an ascorbic-acid derivative that does not oxidize and remains stable even when exposed to light. The results have some dermatologists kvelling: "Not since the introduction of alpha hydroxy acids has there been a more significant advancement in the science of skin care," says Michael Holick, M.D., a professor of medicine, physiology, and biophysics at Boston University Medical Center, who reviewed some of the more than 5,000 before-and-after UV photographs that the company assembled. "The results are very impressive."
Others are determined to marry the new penetration science with powerful botanicals. The Sampar Antidote Complex, for example, combines peptides with extracts of horse chestnut and walnuts for a tri-peptide that Sampar says is as effective as retinoic acid, without any of the irritation. The company claims the tri-peptide stimulates collagen production in cultured fibroblasts by more than 300 percent and decreases the average depth and length of wrinkles by 23 to 39 percent.
Finally, researchers at the University of California-Santa Barbara, after analyzing the properties of 100 chemical-penetration enhancers, just developed 300 more potential enhancers and submitted them to the National Academy of Sciences. While the bulk of this research is still geared toward pharmaceuticals, it won't be long before the results are spun off into products for spas, salons, and department stores. Begovic Johnson expects that as more baby boomers march toward menopause, which can cause profound skin changes, and more scientists work with topically applied estrogen, there will be tremendous breakthroughs in midlife skin care. And Des Fernandes, M.D., a South African plastic surgeon and founder of Environ, a product line with high concentrations of pure vitamins A and C and other antioxidants, expects to see much more research into the anti-aging properties of delivery systems. "If people are going to be living longer, skin care has to become a realistic part of active aging," he says.
As for nanotech, it's not so yesterday yet. But get ready to hear about picotechnology, based on particles that are one-trillionth of a meter.
The Penetration BacklashWith so many products crowing about just how deeply they can penetrate into skin, it was inevitable that there'd be a crop promising to keep more things out. Among those touting greater protection from environmental hazards (usually combined with advanced sun protection) are M.D. Forte's Aftercare Environmental Protection Cream and Aveda's Dual Nature Face Protection. There's even Mustela's Cold Cream Nutri-Protective, which aims to keep cold, wind, and dry air from affecting babies' skin.
Absorption GlossaryAmino acids:Essential components of proteins found in the body. In skin care, serve as collagen-building and skin-smoothing agents as well as antioxidants.
Antioxidants:Substances that inhibit oxidation by neutralizing free radicals, or unstable molecules that essentially rust the body. Examples: beta-carotene, vitamin C, and alpha-tocopherol.
Collagen Fibrous protein:Primary constituent of skin's connective tissue.
Dermis:Skin layer directly below the top layer (epidermis). Consists of connective tissue and contains hair follicles, blood vessels, and oil-producing glands. Elastin Protein similar to collagen. Primary constituent of elastic fibers.
Epidermis:Top five layers of skin, about 100 microns, or one-tenth of a millimeter, thick. Consists of keratinized (protein-hardened) skin cells.
Fatty Acids:Organic acids that facilitate peptide absorption through the skin. Components of lipids.
Fibroblasts:Skin cells found in the mesoderm, the skin's middle layer. Make protein and connective-tissue material such as collagen and elastin. Major target of anti-aging products.
Iontophoresis:Technique that uses an electric current to move a skin-care product or drug through the skin.
Lipid:Component of living cells and intercellular tissue. Lipid fats are used extensively in cosmetics because they easily penetrate the skin.
Liposome:Hollow microscopic sphere used to deliver ingredients into the skin. Easily absorbed because it's lipid based.
Microsphere:Spherical shell that measures one-millionth of a meter, usually made of a biodegradable or absorbable plastic polymer. Filled with a drug or ingredient that is released as the shell dissolves.
Nanotechnology:Processes employing particles that measure one-billionth of a meter or less.
Peptide:Two or more bonded amino acids--a tri-peptide consists of three amino acids; a pentapeptide, five. (Peptides with fewer than ten amino acids are termed oligopeptides; polypeptides have more than ten.) Key ingredient in delivery systems because it easily penetrates the skin, often with a boost from a fatty acid.
Retinoid:Derivative of vitamin A (natural or synthetic). Clinically proven to reverse the signs of aging.
Stratum corneum:Outermost skin layer.
A Pentapeptide's Progress: How one tiny molecule gets deep inside the skin
When skin scientists heard about the discovery of a pentapeptide, a chain of five amino acids that could actually stimulate the deepest layer of the skin to crank out more collagen, they knew it was big news. The only problem was that it had been isolated by National Institutes of Health researchers working on open wounds. Healthy skin--designed to keep foreign materials out--wouldn't allow the tiny molecule to penetrate.
In the case of the pentapeptide, however, explains Mary Begovic Johnson, M.S., a principal scientist in Procter & Gamble's beauty-care division, researchers were able to attach it to a palmitic fatty acid. Once that happens, the molecule--still much smaller than skin cells--can be absorbed by the lipid bi-layer in the epidermis, which transports it into the dermis itself. In this way, the body acts as a traffic cop, directing the ingredient to the fibroblasts, which can put it to use. Here, the protein--labeled as palmitoyl pentapeptide 3 or Matrixyl in such products as Strivectin-SD, Environ's C-Quence, and Olay's Regenerist--has been clinically proven to signal the fibroblasts to produce more collagen and elastin, which in turn produces smoother, firmer skin.
Current Event"It struck me while working with patients how often we would hit a plateau after about ten months or so, and we knew some of it was a question of delivery," says Environ founder Des Fernandes, M.D. "We know vitamin A (retinyl palmitate) penetrates skin very well but vitamin C molecules really struggle to get through. Some people had been experimenting with ultrasound as a way to get the skin to respond better, but we found that had about the same effect as, let's say, wrapping the skin in plastic after a treatment." So Dr. Fernandes developed the Ionzyme DF machine for facials. It combines sound waves and iontophoresis, which he says increases absorption by about 4,000 percent.
Dr. Fernandes was also intrigued by research being done in the U.S. on something called percutaneous collagen induction, which uses microneedles to make tiny holes in the stratum corneum painlessly--the needles penetrate above the nerve level. The openings are massive compared to a molecule of vitamin A. "It's like one person in a big football stadium," says Dr. Fernandes. Using percutaneous collagen induction, he developed the RollCit, a medical device that creates openings that enable vitamin molecules to penetrate deeply into the skin, thereby stimulating the production of collagen in the dermis. He claims the technique produces results similar to laser surgery but without the expense or recovery time. His patients, he says, can be back in public after four or five days.
*The information in this article was accurate at the time it was published on 5/1/06.
___________________________________________________________________
Brought to you by Better Life ProductsWe offer award winning products from Dead Sea Premier Cosmetics that are internationally recognized for their therapeutic and age defying benefits.
Visit us at
http://www.cosmeticsdeadsea.comSign up today for free skin tips and articles at
bhickey@aweber.com
