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NANOTECHNOLOGY

In the deep layers of the skin

Boticário, Natura, Theraskin and Yamá join together with IPT and develop nanocapsules for use in cosmetics

At IPT: Close-up of equipment that allows researchers to experimentally measure the penetration of nanoparticles into the skin

Eduardo CesarAt IPT: Close-up of equipment that allows researchers to experimentally measure the penetration of nanoparticles into the skinEduardo Cesar

Four large companies in the Brazilian cosmetics industry have teamed up to jointly develop technology of common interest that may make project participants more competitive. Conducted in partnership with the São Paulo Institute for Technological Research (IPT), the cooperative project involved the Boticário Group, Natura, Theraskin and Yamá, and led to the creation of two new nanoencapsulation methods for the active ingredients of cosmetics. Under IPT coordination, over two years the group invested R$2.4 million, divided into three equal shares of R$800,000: 1) the institute (which pays for the use of laboratories and the personnel involved), 2) the four companies (which spent R$200,000 each), and 3) the Brazilian Corporation for Industrial Research and Innovation (Embrapii), a public company maintained by the Ministry of Science, Technology and Innovation (MCTI) and the Ministry of Education (MEC).

The end result was a technological platform that is available to the companies participating in the project. During these studies, each company collaborated on research and improved their knowledge of this area. As they are competitors, none of them knew what the others would put into the nanocapsules. What each company wants to use was known only by the IPT team, under a nondisclosure agreement. The idea for the project emerged in 2012 when IPT proposed to the Institute of Technology and Study of Personal Hygiene, Perfumery and Cosmetics (ITEHPEC) —  the virtual technological arm of the Brazilian Association for the Personal Hygiene, Perfumery and Cosmetics Industry (ABIHPEC), whose members include some 380 companies —  to survey members to determine what the industry’s main needs were in the area of new technology development.

“We presented our lines of research and sent a questionnaire to the companies in an attempt to discover what they needed,” says pharmacist Natália Cerize, of the Industrial Biotechnology Laboratory at the IPT Bionanomanufacturing Center, who is coordinating the project. “We found that the highest demand was for nanoencapsulation of cosmetics. In the beginning, 11 companies showed an interest, but this number later fell to nine, then to just four in the end. We then developed the proposal and signed a contract in July 2013, for a term of 21 months,” says Cerize. In 2015, the Brazilian market was the world’s fourth largest, with sales of R$42 billion, behind only the United States, China and Japan.

Two types of nanocapsules or nanospheres were developed as part of the project. The first is like a cell, and the other is solid, like a billiard ball. They are 100 nanometers (nm) to 600 nm in size (1 nanometer is a millionth of a millimeter). Both are made of an undisclosed type of polymer. In the first, the active substance of the cosmetic is protected by a membrane and, in the second, it is mixed with and distributed throughout the mass of the nanosphere. Among the advantages of this technology are protection of the active ingredient to avoid its degradation during application, and controlled release only to the deeper layers of the skin. “The material can be released faster or slower, depending on the effect desired,” says Cerize. The technique also allows more direct dermal absorption and more localized and long-lasting action of the compounds.

Nanospheres, with a rougher surface, on the left in a microscopic image. On the right, nanocapsules with a round surface

IPTNanospheres, with a rougher surface, on the left in a microscopic image. On the right, nanocapsules with a round surfaceIPT

Different designs
Encapsulation is already known and used by some companies manufacturing beauty and hygiene products and drugs abroad, such as the French companies Anna Pegova, Chanel and L’Oréal. In the case of the technology developed by IPT and the four companies, the novelty lies in the design of a platform for different active ingredients, which generated four patent applications. “We determined the best particle size, pH, viscosity, percent of solids and physical-chemical stability for each active ingredient,” says Cerize, who notes that the nanoencapsulation techniques are inspired by the cells of living beings. “They are basically composed of a membrane that protects the nucleus and internal organelles,” she says. “But this membrane also has other functions. It modulates cellular activity, selectively allowing substances into or out of cells.”

In addition to the technological advances, the fact that competitors came together to achieve a common goal, something unusual in Brazil, is drawing attention. “In this project, everyone cooperated to be able to do something bigger and better than would be possible if each worked independently.” According to Cerize, the technology developed will not be used just for those specific active ingredients tested during the study, but also for new products developed by each company in the future.

“For more complex products it is essential that companies band together — including competitors — in the pre-competitive research and development (R&D) phase to share the costs and also the risks of developing immature technology,” says Humberto Pereira, vice president of the Brazilian Association for Research and Development of Innovative Companies (Anpei). “Technological partnerships between competitors is widespread in the United States, such as the NextGen program to modernize air traffic control, and in the European Union, such as the Framework Program, also a partnership, covering areas such as health, nanotechnology and transport.”

Professor Rosiléia das Mercês Milagres, of the Dom Cabral Foundation in Nova Lima, Minas Gerais State, recalls an important example of competitors participating in a cooperative project. “The Genolyptus (Brazilian Eucalyptus Genome Research Network) project, which undertook genetic mapping of the eucalyptus tree from 2002 to 2008, involved 12 forestry companies such as Klabin, Suzano and Votorantim, seven universities and Embrapa,” says Milagres. Among the advantages of this type of group are the reduction of risks and the sharing of benefits at lower cost. “Cooperative projects produce quality results at an amazing pace and low cost,” says agronomist Jefferson Luís da Silva Costa, a researcher and advisor to the Embrapa Research and Development Board in Brasília.

IPT Industrial Biotechnology Laboratory: reactor where nanoparticle solutions are prepared

Eduardo CesarIPT Industrial Biotechnology Laboratory: reactor where nanoparticle solutions are preparedEduardo Cesar

Knowledge and training
In the first phase of the project two nanoencapsulation platforms were developed. In that stage, called pre-competitive, there were joint activities involving IPT researchers and the companies’ technical teams. Ten institute representatives and 23 company and ITEHPEC representatives participated directly in the activities. The advances of the research and the knowledge generated were shared during six collective meetings and two courses held at IPT, covering theory and practical questions. There were also more than 30 individual meetings (IPT staff with representatives from each company) and about 500 hours of various activities to train company professionals. The second phase was individual and confidential between IPT and each of the partners, who worked with the active ingredients of interest to them to find solutions tailored to their product line. Confidentiality clauses were signed to protect industrial secrets.

The experience was positive. “The project’s working method interested us greatly because it used a methodology that, in addition to providing technological development, can result in competitive and economic advantages,” says Deli Brito de Oliveira, manager of Research, Development and Innovation at Theraskin Farmacêutica. “Professionalism guided discussions and enabled the success of the endeavor, resulting in gains for all. We had the opportunity to learn about and internalize a new culture of innovation and technology. ”

For Gustavo Dieamant, Technological Research Manager of the Boticário Group, the cooperative design model is very good for encouraging applied research that requires major investments. “Each partner contributed his knowledge and that provided quick and effective results. We took a chance on new collaborative models involving a division of financial and economic resources and risks,” says Dieamant.

Fabio Yamamora, technical director of Yamá, says that the company’s participation in the project was a strategic decision made to serve the cosmetics market, which is also very challenging. “Every three months there was a general meeting in which we aligned the knowledge generated from encapsulation methods, but without giving details of the active ingredients chosen by each participant,” says Yamamora. For Luciana Hashiba, Natura Innovation Manager, the largest gain was the partnership with IPT, which interfaced with each company and developed the technology. “Afterwards, each participant continued developing the methodology,” she explains.

In the case of Natura, Hashiba also says that nanotechnology is critical to providing the consumer with a different cosmetic sensory experience, with increasingly effective skin treatment and protection, in addition to safe products that allow the release of active ingredients in a more controlled manner. “In our organization, innovation arises mainly from different forms of collaboration,” says Hashiba. “Open innovation, as in this case working with IPT, has great potential to leverage results for us and for the network involved in this type of project.”

Researcher operates skin penetration equipment

Eduardo CesarResearcher operates skin penetration equipmentEduardo Cesar

Mastery of the technology
Hashiba says that Natura hopes to incorporate the technology if it proves viable in subsequent steps in the development of new cosmetics. “We still need to follow various processes and methodologies to ensure its safety and efficacy, as we do with all our products,” she explains. “If all goes well, the innovation will make a difference in our line.”

Yamá also intends to use the methodology as a foundation for the future development of other nanoencapsulated active ingredients. “We expect to improve the quality of the manufacturing process, reducing the irritability of some active ingredients and increasing the compatibility of the raw materials,” says Yamamora.

Simone Tiossi, Theraskin Director of Operations and Innovation, says that the introduction of nanotechnology in the company will result in great benefits because it can be extended to other product lines and also drive new developments after the technology is implemented. “This project was the first step to accumulating the knowledge necessary to master this technology, which has been widespread worldwide, providing solutions to problems not even envisioned previously,” explains Tiossi. The results of working with the IPT are also considered promising by the Boticário Group.

“The next step will be to conduct a methodology escalation study, as well as in vitro and clinical studies to ensure its safety and efficacy,” says Dieamant. “So far the project has been conducted on a bench scale. Now we, ITEHPEC and the four companies are evaluating the possibility of continuing, in a new phase of the project, to work on ramping up production of the encapsulated ingredients within the production environment of each participant,” says Cerize, of IPT.

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