Category Cosmetic Formulation of Skin Care Products

THE SKIN CARE MARKET

More effective anti-aging ingredients and formulations are being developed every day. Cosmetic alternatives to dermatological procedures will be increasingly available for the average woman, and technical innovations to cosmeceuticals will allow skin care products to deliver active ingredients more effectively and with greater precision. Emerging genetic-based technology will enable the development of targeted products that are customized to meet the needs of today’s individual man or woman. In addition, the growing concern for personal health will further expand the nutraceutical market. With the increase in consumer expectations and the continuation of changing trends, the collaboration between the dermatology professional community and skin care product innovators must continue to be fostered.

NEW USERS

Male grooming is one of the fastest growing sectors in the cosmetic industry (23). There are significant differences between men’s and women’s skin; men’s skin tends to be less acidic, thicker, oilier, and hairier (24,25). By using products developed specifically for their skin type, men will achieve better results. Products being developed particularly for men include not only moisturizers, but also products to combat aging, self-tanners, blemish-control products, concealer products, and bath and shower products. These cosmetic products will be developed and promoted to seem masculine, so that the average male will feel comfortable using them. Consistent with this trend it is expected there will be an increase in male visitors to the dermatologist’s office for cosmetic procedures.

DELIVERY SYSTEMS

Active research continues in the area of delivery systems for cosmetic products. Particulate delivery systems such as liposomes, which are tiny, hollow lipid spheres, are used to carry active ingredients into the skin. However, smaller, more specialized transportation systems are being developed; these include nanoparticles, microcapsules, and millicapsules.

Nanotechnology is making its way to the forefront of the cosmetic industry. Nanoparticles are solid hydrophobic spheres with an average particle size of less than one micron; they have high cationic charge density to improve their deposition onto the target site and prevent them from being washed off during rinsing (22). This bioadhesive quality also reduces the need for reapplication. The hydrophobic quality of the nanospheres sustains the diffusion rate of the active ingredients, which allows their release over an extended period of time. The nanospheres have improved stability when compared with emulsion – based delivery systems, such as liposomes. This enhanced stability prolongs product shelf life. In addition, the substance to be delivered does not have to be soluble in the vehicle, since it can be dispersed in the solid matrix. Incorporating an ingredient such as a sunscreen into nanoparticles in a skin care product allows the product to block UV light, but does not interfere with the look and feel of the lotion. As nanotechnology advances, it may enable the development of more customized and effective personal care products.

SKIN TONE ALTERATION

Skin tone is an area of dissatisfaction for many women around the world. Clear, fair skin tones are the goal in Asia, and skin lighteners have been popular there for many years. However, they are now gaining popularity in the west as well. They can also be used to treat disorders of hyperpigmentation, such as age spots. Tyrosinase is a key enzyme in the production of melanin. Phenolic skin lightening agents such as hydroquinone interfere with melanogenesis by acting as competitive inhibitors of tyrosinase, so that the skin is less pigmented. Non-phenolic skin lightening agents, including glucosamine, kojic acid, azelaic acid, and licorice extract, also inhibit tyrosinase activity. Skin lightening agents are now being incorporated into bar soaps and color cosmetics as well.

In western countries, where darker skin is often idealized, self-tanners continue to increase in popularity. These usually contain dihydroxyacetone, which reacts with keratin protein in the stratum corneum to form melanoidins to give the temporary brown color to the skin. Because the stratum corneum is continually sloughed, the results are temporary. Manufacturers continue to work toward developing self-tanners that are odorless, quick to dry, and unlikely to streak (19). They also are working to improve delivery systems, including wipes, sprays, and foams.

Optical technology is now being incorporated into products to improve the appearance of skin. These new products do not change the skin at all, but when they are applied to the skin, they improve its appearance. The basis for this technology is that tiny particles can reflect and emit visible light from the skin. When used in cosmetics, the resultant reflected light can help hide wrinkles, large pores, and even cellulite and make the skin appear healthier (20).

Cosmetic companies continue to actively research and promote products to decrease cellulite. Ingredients such as caffeine, kiwi and green apple extracts, shiitake mushroom extract, gingko biloba, and seaweed extracts are all being incorporated into products

intended to firm the skin, increase elasticity, and decrease cellulite (21). Although none of these products have delivered the cure, women everywhere continue to have hope.

CUSTOMIZED PRODUCTS

The genomics revolution has already begun to transform the pharmaceutical industry, and it is now making its mark on the cosmetic industry as well. At the heart of this revolution is the ability to generate and assemble massive amounts of DNA sequence information. We are now able to identify key genes in biological processes such as skin aging through a method called gene expression profiling. Single nucleotide polymorphisms (SNPs) represent the genetic basis for inter-individual differences in disease susceptibility, including aging. The identification and mapping of these SNPs is an area of active biotechnologic research.

As a result of these advances, two promising applications of the genomics revolution are beginning to develop: (i) the use of an individual’s DNA sequence information as the basis for the development of improved clinical study design and preventative and diagnostic strategies and (ii) the use of DNA sequence information to develop personalized medicines and products. There are several factors that will influence when and how the DNA sequencing will be applied to the development of cosmetic products (18). These include the progression of the science, consumers’ willingness to use their DNA sequence for product choices, and market considerations. Ideally, this genetic technology will allow cosmetic companies to identify specific skin qualities—such as texture, pigmentation, hydration, and wrinkles—and alter products to meet individual skin needs.

MEDICAL MIMICS

The growing demand for anti-aging products has led to the development of “medical mimics.” These are new cosmetic alternatives to costly dermatologic procedures and surgeries. “Facial relaxers” are gaining popularity as an alternative to Botox injection. Argireline, a synthetic peptide that has been touted to relax facial muscles by inhibiting the neurotransmitter catecholamine, has been advertised as having impressive wrinkle reduction effect (17). Several companies have developed home products that mimic microdermabrasion. These products use lower dose crystals and sometimes a warming agent to smooth, polish, and resurface the skin, producing results similar to office dermabrasion. Utilizing lower levels and less aggressive chemical peel acid ingredients, at-home chemical peels have also become popular. While home laser treatments are not yet available, it is expected that low dose home lasers are in the not so distant future for skin texture improvement and hair removal. It is expected that the “medical mimic” trend will continue as women try to balance their busy lives.

NUTRACEUTICALS

Nutraceuticals provide beauty benefits from the inside out; their goal is to enhance beauty by improving health. There are several dietary supplements that have been developed to promote skin health in particular. These supplements provide vitamins and nutrients especially involved in skin physiology. The challenge for the nutraceutical industry is to definitively measure the benefit of these oral supplements in clinical testing. In the future it is expected that more published clinical data will be available, as well as industry – regulated labeling systems to describe the claimed benefits.

What Is Next in Skin Care Cosmetic Products?

Lauren A. Thaman

P&G Beauty, Sharon Woods Technical Center, Cincinnati, Ohio, U. S.A.

The cosmetic industry has changed dramatically over the past 20 years with the introduction of daily UV lotion in the late 1980s to fight future aging. No longer are women searching for hope in a jar but focusing on the latest over-the-counter breakthrough products with clinically demonstrated biological activity. This quest for skin health and youthful beauty has driven many consumers to explore a variety of approaches. It has also triggered a renaissance in the world of skin care where health, beauty, and technology are converging to create new and exciting opportunities.

This frantic search for beauty and youth has stimulated a remarkable growth in the skin care industry. Skin care advances are moving quickly as they mirror advancing technology in pharmaceuticals and biotechnology. Global retail sales of anti-aging skin care products have increased 71% since 2000 (1). In 2004 skin care sales topped $12 billion, with $7 billion of that being spent on facial treatments alone (2). As biotechno­logical and pharmaceutical research continues to result in technologic advances, skin care companies will continue to spend millions of dollars on incorporating these advances into skin care products. The average woman will find more choices to aid her in the battle against aging, including customized products and new novel ingredients with increased effectiveness and more precise delivery.

COSMECEUTICALS

Clearly cosmeceuticals are the fastest growing segment of the skin care market (3) and are currently the driving force in the field of skin care research (4). Cosmeceuticals are cosmetics that contain biologically active ingredients, and while these ingredients are not classified as drugs, they do have documented functional treatment benefits. When cosmeceuticals are labeled and marketed as cosmetics, they are not regulated by the FDA.

Cosmeceuticals are used primarily to combat the effects of aging on the skin. More women are yearning for healthy, youthful skin, fueling the demand for these anti-aging products. Younger women are also looking to these products as a preventive strategy against aging. Cosmetic companies are investing millions of dollars to develop new and

better actives for anti-aging products, and women of all ages are constantly trying the newest product and consulting their dermatologists for therapeutic approaches to fight the signs of aging.

Retinoids are the most recognized anti-aging ingredient, comprising a family of compounds with structures and mechanisms of action that resemble those of vitamin A. Retinoids are essential nutrients which play a role in cell growth and differentiation (5). Tretinoin, the most popular retinoid, increases dermal collagen, cellular differentiation, and proliferation. It has been shown to improve skin’s global appearance, particularly affecting fine and coarse wrinkling, roughness, pigmentation, and sallowness (6,7). However, tretinoin is a drug regulated by the FDA. Retinol, first generation retinoid, is often added to over-the-counter cosmetics (8). Retinol must be converted to retinaldehyde and then to all – trans-retinoic acid within the keratinocyte to become active (9). Because retinol is a cosmetic ingredient, it is not labeled as an active ingredient. While not labeled as such, many published studies demonstrate the significant biological action and efficacy of this cosmetic vitamin A derivative. Retinoids and other alternate metabolisms of vitamin A will continue to be key mainstay cosmeceutical ingredients.

Another popular cosmeceutical affecting cellular proliferation is alpha-hydroxy acid (AHA). AHAs increase the type I collagen, mRNA, and hyaluronic acid content of the epidermis and dermis (3). They also renew the stratum corneum by promoting desquamation. Glycolic acid, lactic acid, and malic acid are all examples of AHAs. Newer generation polyhydroxy acids are also being studied; these PHAs provide additional moisturization compared to AHAs, and do not cause the irritating response associated with AHAs (10). They also possess antioxidant properties (10).

A major class of cosmeceutical ingredients is antioxidants that mediate free-radical damage from UV radiation. Since the skin’s own supply of free-radical scavengers is limited, topical antioxidants, which scavenge free radicals and protect cells from damage, can attenuate skin damage from UV radiation. Topical antioxidants include vitamins C and E, alpha-lipoic acid (ALA), and coenzyme Q10. In addition to their antioxidant effects, these agents all have other documented anti-aging properties. Vitamin C has collagen stimulating properties and has been shown to be photoprotective (4). Vitamin E decreases free-radical production as well as inhibits collagenase production (11). ALA is a strong intracellular free-radical scavenger (12). It also has anti-inflammatory action, inhibiting the production of pro-inflammatory mediators (3). Coenzyme Q10 (ubiquinone) is present in every cell in the body and acts as a coenzyme in energy production. It has also been shown to improve skin texture (13). One of the bigger challenges to the future use of antioxidants is assuring biological activity from a cosmetic preparation and measuring the antioxidant benefit in a clinical environment. As these challenges become resolved, a significant increase in use and benefit of these ingredients is expected.

The renewed focus on health in today’s society has also created a niche for natural and organic products. Women are interested in natural ingredients that make therapeutic claims. This has led to increased popularity of skin care products containing plant or mineral ingredients, especially in the spa market. Organic advocates are willing to pay extra for skin care products that are clearly organically produced (14). Therefore, one of the hottest areas for cosmeceutical ingredients is the utilization and understanding of botanicals. Topical botanicals have been shown to combat reactive oxygen species, as well as often having various secondary effects. Some strong botanicals include tetrahydro- curcumin, pycnogenol, silymarin, and soy extracts (15). The usage of botanicals for their anti-inflammatory function continues to grow. Botanicals have been shown to block inflammatory changes that may result in cutaneous aging. Some common anti­inflammatory botanicals include aloe vera, green tea, and allantoin (15). However, some

newer research suggests the molecular structure, as well as the formulation delivery system, strongly affects the biological activity of botanicals. Understanding the effect and potential of botanicals as cosmeceutical ingredients will likely continue to be a key industry focus.

There are several different types of growth factors of both plant and animal origin that have been incorporated into cosmeceuticals. Furfuryladenine (kinetin), a synthetic plant growth factor that delays senescence of plant cells, has shown in vitro benefits in retarding cellular aging (16). Transforming growth factor-beta 1 is an important human growth factor with therapeutic potential because of its role in neocollagenesis (3). Human growth factors are relatively under explored by the cosmetic industry today and given the negative public view associated with this class of ingredients it is unlikely that they will be a top focus area in the coming years.

Stimulating the skin’s natural repair and rejuvenation system by topically adding skin functional ingredients like peptides, hyaluronic acid, niacinamide (vitamin B3), estrogen, and dimethylaminethanol will continue to show promise in improving the appearance and texture of skin. Delivering these relatively large molecules to the biological key targeted area to maximize the effect remains the key barrier to skin aging damage reversal or stimulation. Research in this area will continue with the next wave of cosmeceutical ingredient breakthroughs.

Substantiation of Efficacy

Ubiquinone’s antioxidant action in skin was confirmed in vitro by sophisticated ultra-weak photon emission (UPE) (169). Increased antioxidants result in decreased UPE. Elderly volar skin demonstrated 33% reduction in antioxidant activity when compared with young skin. This was corrected after one week of twice-daily topical application of 0.3% ubiquinone. After UVA irradiation, a decrease in antioxidant activity was noted; this loss was significantly corrected with topical 0.3% ubiquinone.

The efficacy of ubiquinol in reversing photoaging was further studied clinically (168). Ubiquinol cream (0.3%) was applied to one-half of the face and placebo to the other once daily for six months. Casts were made of the periorbital rhytides. The improvement can be appreciated in the photographs shown in Figure 15. Quantitative microtopography demonstrated a 27% reduction in the mean wrinkle depth.

Another clinical measure of photoaging is stratum corneum cell size. With deceased cell turnover time in aged skin, comeocytes become larger. Treatment once daily for six months with ubiquinone cream decreased corneocyte size equivalent to rejuvenation of 20 years (168). Thus, ubiquinone is be an effective antioxidant protecting the dermal matrix from both intrinsic and extrinsic aging, making it a potentially important cosmeceutical.

SUMMARY

Nutritional antioxidants represent a novel category of cosmeceuticals. There is no doubt that higher levels are achieved in the skin through topical application than with oral

supplementation, thus providing a protective antioxidant reservoir in the skin. Current research indicates that topical vitamin E and C and L-SeMet provide UV photoprotection and reverse photoaging. Ubiquinone and genistein may provide photoprotection. In addition, they as well as topical a-lipoic acid may retard both intrinsic aging and photoaging. There is further evidence that a-lipoic acid and ubiquinone may also reverse photoaging. Thus, topical antioxidants continue to be an important area of cosmeceutical research.