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Well-grounded Beauty

Group of researchers and companies prepare nanocosmetics with a variety of uses

ABIURONanocosmetics entered the global market 15 years ago thanks to Lancôme, a French company, which is the luxury products division of L’Oréal, when the company launched a facial, anti-ageing cream transported by pure Vitamin E nanocapsules to prevent the skin ageing. The nanotechnological development came from the University of Paris 11, which patented the innovation and licensed it to the company. Ever since, a number of global cosmetics giants have invested in research to develop this line of products. In Brazil, the interest in nanotechnology applied to cosmetics is relatively recent, yet it is involving a rising number of companies and researchers from the country’s major universities. For a product to be a nanocosmetic, it must contain organized structures smaller than 999 nanometers (one nanometer equals one millionth of one millimeter). “Cosmetics is a field that has a future in nanotechnology, which led the Ministry of Science and Technology (MST) to create and implement the Nanocosmetics Network in 2005,” says coordinator Silvia Guterres, a professor at the Department of Production and Control of Medical Drugs at the College of Pharmacy at the Federal University of Rio Grande do Sul (UFRGS). This network is part of a package to encourage nanoscience and nanotechnology implemented in 2001.

The Nanocosmetics Network consists of researchers from Brazilian universities and research centers that have scientific collaboration agreements with foreign researchers and research institutions. Besides UFRGS, the Brazilian partners include the University of São Paulo (USP) – São Paulo and Ribeirão Preto campuses, the IPT Technological Research Institute at the State University of Campinas (Unicamp) and the Federal University of Rio de Janeiro (UFRJ). The international collaborators are connected to universities in France, Switzerland, Sweden, Germany, England and Holland. “We focused on cosmetics because of the opportunity. But my professional expertise, as is that of most of the network’s members, is in the field of medical drugs,” says the coordinator. Silvia helped to develop the first Brazilian nanotechnology-based drug, more specifically, a skin nanoanesthetic developed by a São Paulo company called Incrementha, a joint venture between pharmaceutical companies Biolab and Eurofarma (read more about this in issues 135 and 143 of Pesquisa FAPESP).

At present, nanotechnology in cosmetics is focused mainly on products for facial and body care with anti-ageing and photo protection properties. “The nanostructures are real reservoirs that control how deeply the cosmetic penetrates the skin and the speed with which the active principle is released,” explains Silvia. “Concentrations of gradually released active principles do not reach toxic limits and enable a constant supply to the different layers of the skin.” The result of this kind of action is improved efficacy at lower doses.

The interest of cosmetic manufacturers in nanotechnology can be gauged by the secrecy around the agreements and contracts signed with Brazilian universities. Here, the popular saying that secrecy makes for good business is taken seriously. And no wonder this is so, as this field is expanding greatly in Brazil. Today, the country ranks as number three on the global cosmetics list, right behind the United States and Japan. In just two years, from 2005 to 2006, it overtook traditional markets like France, Germany and England. “This gives you an idea of the importance of cosmetics in an underdeveloped country,” says Silvia. In 2007, the revenues of companies in the personal care, perfume and cosmetics industries totaled R$ 19.6 billion, an 11.5% increase relative to 2006. Studies show that the consumption of cosmetics in Brazil doesn’t differ between social classes,” says Silvia. “The money that a class A, B, C, D or E consumer spends on cosmetics in proportion to his or her income is basically the same.

The amount invested in cosmetics is different.” The cosmetics market is very dynamic and products are constantly being renewed, contrary to what happens in the drugs industry, where it takes a very long time for a new product to be developed and launched on the market, where it remains for many years. “The field of cosmetics is teaching us many things and as we draw closer to the end of a technological cycle this also becomes useful for the development of drugs,” says Silvia. “These two industries feed off each other.” In Brazil, O Boticario was the first company to develop and launch a nanocosmetic product, namely an anti-ageing cream for the eyes, forehead and lips called Nanoserum. Its nanostructured composition includes active ingredients such as vitamins A, C and K and a product to lighten the skin. The technology, developed in conjunction with French laboratory Comucel, involved an investment of R$ 14 million and is part of the Active line of products, launched in 2005. In 2007, Natura introduced Brumas de Leite, a body moisturizer whose particles were about 150 nanometers large.

Biocompatible system
There is a trend toward market expansion. Therefore, companies are always attuned to the innovations developed at the forefront of research. The group led by professor Maria Helena Andrade Santana, from the College of Chemical Engineering at Unicamp, which is also part of the Nanocosmetics Network, for example, is working with Chemyunion – a Brazilian producer of cosmetic and pharmaceutical raw materials – to develop nanotechnology-based products. The USP Innovation Agency is negotiating with a company the technology transfer for an innovative and biocompatible system, developed by a group coordinated by professor Maria Vitória Lopes Badra Bentley, from USP’s College of Pharmaceutical Sciences in Ribeirão Preto. This college is also a member of the network, having been awarded the 2006 Capes Thesis Award in the field of pharmaceutical sciences. The award is granted annually by the Capes, the Coordinating Office for the Improvement of Personnel with Higher Education.

ABIURO“This increases the active ingredients’ penetration of the skin and transports them,” says the researcher. As the legal process is yet to be completed, she cannot provide details on this system’s innovative aspects, but she mentions that it involves neither liposomes (nanostructures that resembles tiny drops of fat) nor solid nanoparticles, but she hints: “We achieved an excellent skin penetration rate by using this system with peptides, which are relatively big molecules for the purpose of skin penetration,” she says. “The application is very interesting for skin care and cosmetic products,” adds Maria Vitória, who cannot disclose further details on the matter.

The researcher’s group also maintains cooperation agreements with several companies to develop and evaluate the efficacy of new products. “We pioneered the development of in vitro methodology for the evaluation of skin penetration, the results of which can reflect the safety and quality of topical products,” she says. The tests are conducted on hog’s ear skin, a tissue that is very similar to human skin. The skins are dissected, and mounted on glass devices called diffusion cells; the formula is then placed on these skins. “We evaluate the diffusion of the pharmaceutical product through the skin and we also check on which skin layer it was retained,” she explains. This method allows one to work with several preparations and achieve greater results in reproduction. “This method is easier than working with several different animals, as there is less interference such as stress and other physiological reactions, and it facilitates the identification of the product’s penetration ,” says Maria Vitória. “Additionally, any cosmetic product that relies on animals cannot be registered in Europe,” the researcher points out. She has already conducted skin penetration tests for Natura.

Hair care is another promising field for nanocosmetics. Researcher Valéria Longo, from Liec, the Interdisciplinary Laboratory of Electrochemistry and Ceramics, , which is part of the Multidisciplinary Center for the Development of Ceramic Materials at the Federal University of São Carlos, submitted a project for approval by Finep, the Projects and Studies Financing Agency. The objective of the approved project, to be conducted jointly with Kosmoscience, a cosmetics company from the town of Valinhos, is to produce a nanoemulsion for hair straightening. “Because of the small particles, one can make an emulsion that not only ensures this feature along the entire strand of hair, but also covers the hair fibers more efficiently,” says Valéria. “The advantage is that the nanoemulsion, unlike ordinary hair straightening products, doesn’t destroy the outer structure of the hair fibers, called cuticles, to penetrate into the hair strands.” And this happens because hair strands contain microtubes that permeate small molecules such as water. The nano-level product takes advantage of this natural path of the hair. The group headed by professor Maria Helena joined Chemyunion to develop technology to produce serycin nanoparticles (the silk protein), used to manufacture a product – called Seriseal – that seals the cuticles of the damaged hair strands. “This product makes hair look healthy again,” says the researcher. The product should be launched by the end of the first half of the year.

New nuances
There are other ways to use nanoparticles. Companies such as L’Oréal believe that in the future their portfolio of cosmetic products will be based on nanopigments. “We will be able to obtain color shades we have never seen before, with many more nuances,” says Silvia. Brazilian nanotechnology developments are forwarded to the Nanotechnology Network, a virtual research group whose aim is to go through all the cycles of the development of a product, thus generating Brazilian expertise in this field. The network chose sun block as its model for studying. “A group from UFRJ, for example, is working on the allergic possibilities of skin products using the study model. Two other groups, one from IPT and one from UFRGS – which are at the other end of the production cycle – are working on large-scale production,” Silvia reports. The network is a catalyst to encourage closer contact between universities and the business community. “When the network was organized, it added researchers working on nanotechnology research projects, the results of which could be applied to cosmetics,” says Maria Vitória.

Before joining the network, the group coordinated by the researcher was working on the development of topical skin care products for therapeutic and cosmetic purposes. Maria Vitória, who has worked with skin permeation for 17 years, explains that there is no difference between encasing an active ingredient in a capsule for skin inflammation and encasing a vitamin for cosmetic results. However, before choosing the most suitable nanotechnological system to carry an active ingredient, one must know where the product is to be delivered, the size of the active molecule, and other variables. “There are chemical, biological, physical and technological factors involved in finalizing a quality product,” says Maria Vitória, who was granted FAPESP funds to purchase the equipment used in nanotechnology.

Unique effect
“A cosmetic is traditionally defined as a product that doesn’t penetrate the skin and has a mainly sensory activity,” says Maria Helena. When the molecules of the active principles in creams are bigger, they remain on the surface of the skin, protecting it from water loss. This produces a purely cosmetic effect. “At present, there is a lot of emphasis on derma-cosmetics, which has a different action in terms of their application.” This is precisely the kind of action that is sought for nanocosmetics. The aim, more specifically, is more effective on wrinkles and for fillers, thanks to deeper penetration of the particles into the skin, but without allowing the product enter the bloodstream. “At our lab, we’re also working with polymer nanoparticles of hyaluronic acid and elastic liposomes, both of which have more powerful skin penetration properties, yet do not allow the cosmetic to reach the derma, the deepest of the skin’s layers,” she says.

The liposome work is in line with modern nanotechnology strategies, such as the capsule that carry the active ingredients. Phospholipids, like those in our body, are the liposome’s structural component. To penetrate the skin, their surface is modified with biocompatible polymers, which makes them flexible or elastic. This is the case because, in order to carry a significant amount of the cream’s active ingredient to the skin’s deeper layers, one must build particles measuring about 100 nanometers. As most of the skin’s pores measure 30 nanometers, the liposome has to be deformed, while maintaining its wholeness, in order to go through the pores and penetrate the epidermis. The polymer that is placed on the surface has to be highly hydrophilic, i.e., it must capture a lot of water, stabilizing and protecting the liposome from attrition as it goes through the pore. “This is different in relation to other nanoparticles and demands engineering knowledge on the permeation of the particle into nanopores, to achieve the sought-after results,” says Maria Helena.

Besides liposomes, polymer nanoparticles and solid lipids are the other nanostructures most widely used to encase the active ingredients. There are two kinds of polymer nanoparticles: the matrix, or nanosphere, comprised only of polymers, and the vesicular, or nanocapsule, made of oil and covered with a polymer. Both are used to encase lipophylic active ingredients, which have a powerful chemical affinity with fats. Solid lipid nanoparticles are also used to carry lipophylic compounds. “The strong appeal of these kinds of nanoparticles is the production technique, which is easily staggered for quick industrial application,” says professor Adriana Pohlmann, from the UFRGS Chemistry Institute and the network’s vice coordinator. “Perfumes like Chanel’s Allure have micelle nanostructures that control the gradual release of some scents, enabling them to linger for longer,” Silvia exemplifies.

ABIUROThe nanoparticles used in cosmetic products are divided into two groups: labile and insoluble. The labile ones dissolve physically or chemically after they are applied to the skin, which is the case of liposome and biodegradable nanoparticles. The insoluble particles, such as the fullerenes and nanotubes (nanometric structures composed of carbon) and quantic points (tiny semiconducting particles) do not deconstruct in biological environments. This classification, proposed by the European Union’s Scientific Committee for Consumption Products in 2007, was created to differentiate the hazards of the different nanostructures. The classification derived from the doubts as to the safety of using metal oxides (such as titanium oxide and zinc oxide) in sun blocks. “The choice of the labile or insoluble particle is made at the start of the process because one must foresee how it is going to be included in the formula, how it is going to release the active ingredients and what will happen after it performs its functions,” says Adriana.

Safe product
Most products on the market are basically comprised of nanostructures based on biodegradable polymers or phospholipids, such as soybean lecithin, which are biocompatible and biodegradable. When the product, such as some sunblocks, contains insoluble nanoparticles, it is necessary to check the product’s safety, especially when the particles’ diameter is under 100 nanometers. “Above this, they tend to be retained in the corneal stratum, the upper layer of the epidermis. They are eliminated when the skin renovates itself,” says Adriana. Sunblocks can be physical or chemical. To develop sunblocks with higher solar protection factors, the standard procedure is to combine both types. Chemical sunblocks contain organic molecules that absorb ultraviolet radiation. Physical sunblocks contain inorganic, insoluble particles that reflect the UV rays. “When the particles are very big and the objective is to block solar radiation, the sunblock applied on the body creates a whitish layer,” says Adriana. To obtain the same protection and a more transparent effect, one must reduce the size of the particles. This is what companies have been doing – reducing the particles from a micrometric to a nanometric scale, while maintaining the same solar protection factor. “These particles are often smaller than 100 nanometers and can enter the bloodstream,” says Adriana. She points out that one can prepare formulas with less than 100 nanometers, provided that trials are conducted to prove the product’s safety.

The safety issue was the main topic of the III International Dialogue on Responsible Research and Development of Nanotechnology, held on March 11 and 12, 2008 in Brussels, Belgium. This was attended by representatives from the European community, the United States, Japan, Australia, and Brazil, among others. “The most responsible position is to remember that there is a possibility of some hazard whenever a new product is being used, whether or not it is a nanotechnological product,” says professor Mario Baibich, general coordinator of Micro and Nanotechnology at the Ministry of Science and Technology. At the meeting, it was also emphasized how important it is to check how much nanotechnology the new product actually contains. “Many cosmetics are launched with a nanotechnological appeal when in fact the size is in micrometers,” points out Baibich.

In addition to this check, it is also necessary to evaluate, according to the size and the composition of the particles, whether or not the product is able to penetrate the human body through the cell walls. “This makes nanotechnology more expensive, because a responsible party will follow all the scientific parameters before marketing a new product,” says the professor. Nanometrology is one of the ways of controlling the size of the particles being manufactured and Brazil’s Inmetro (National Metrology, Standardization and Industrial Quality Institute) has started doing these analyses recently.

It is difficult to estimate how many nanotechnological products are currently found on the global cosmetics market, because there is no legal obligation to provide information on nanoparticle content in cosmetics. Sometimes, a company specifies on the package that the product contains nanoparticles without specifying their size. “We conducted a survey in Brazil on products that mentioned nanotechnology on their packaging and we found that some of the packaging referred to them in such a way as to induce consumers to think that they contained a nanotechnological component, but due to the price of the product, it was obvious that this was impossible,” says Silvia.

“Nanotechnology imposes a certain cost upon the product.” Primordiale, the first nanotechnological anti-ageing cream launched by Lancôme, costs R$ 289.00 on the company’s site. Akinésine, a similar product manufactured by Anna Pegova, costs R$ 378.00. These prices are much higher than those charged by these companies for anti-ageing creams without nanotechnology, whose pricing is, on average, R$ 80.00 to R$ 120.00.

The Project
Multi-user laboratory for the characterization of systems for the release of micro and nanodispersion in pharmaceutical products; Type Multiuser Equipment Program; Coordinator Maria Vitória Bentley – USP; Investment R$ 364287.32 (FAPESP)