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The book "Nanocosmetics and nanomedicines: new approaches for skin care” contains a summary of the most important nanocarriers for skin delivery. Although “nanocosmetics” is a subject widely commented in the academy and the beauty industry, a book covering the skin care treatments using nanotechnological approaches with cosmetics and nanomedicines is still missing, therefore the need for this publication. This book is divided in three parts: The first one (Part A) is devoted to a brief review on the main topics related to the skin delivery and to the introduction of the subject “nanocosmetics”. The second part (Part B) presents different types of nanocarriers applied as skin delivery systems for cosmetics or drugs. The last part (Part C) shows a wide range of applications of nanotechnology on the skin care area as well as on dermatocosmetic and dermatological fields.



Fundamentals of Skin Delivery


Transport of Substances and Nanoparticles across the Skin and in Vitro Models to Evaluate Skin Permeation and/or Penetration

Nanotechnology can be used to modify the drug permeation/penetration of encapsulated substances, through the manipulation of many different factors, including direct contact with the skin surface and controlled release. In general, nanoparticles cannot cross the skin barrier, which can be explained by the cell cohesion and lipids of the stratum corneum, the outermost skin layer. The device most commonly used to study the transport of substances and nanoparticles across the skin is the Franz vertical diffusion cell, followed by the substance quantification in the receptor fluid or determination of the amount retained in the skin. Microscopy techniques have also been applied in skin penetration or permeation experiments. This chapter will present the fundamental considerations regarding the transport of encapsulated substances and/or nanoparticles across the skin, the experimental models applied in these studies and a review of the main studies reported in the literature in order to allow the reader to gain insight into the current knowledge available in this area.
Renata V. Contri, Luana A. Fiel, Adriana R. Pohlmann, Sílvia S. Guterres, Ruy C. R. Beck

Rheological Behavior of Semisolid Formulations Containing Nanostructured Systems

This chapter presents an overview of the rheological properties of semisolids before and after the incorporation of nanostructures. Theoretical concepts as well as practical applications are described in order to show the influence of the rheological properties on the physicochemical and biological characteristics of formulations containing nanosystems.
Marta P. Alves, Renata P. Raffin, Solange B. Fagan

Nanocarriers for Skin Care and Dermatological Treatments


Polymeric Nanocapsules: Concepts and Applications

This chapter presents an overview of polymeric nanocapsules for dermatological and cosmetic applications, including their preparation methods, physicochemical characterization and models of supramolecular structures. Polymeric nanocapsules are advantageous because of their ability to control the release rate and the penetration/permeation of drugs and active ingredients in the skin. These properties can be modulated through manipulating the qualitative and quantitative compositions of formulations. The chemical nature of raw materials can define the supramolecular structures of the nanocapsule core and surface. In addition, polymeric nanocapsules protect the encapsulated drug or active ingredient from degradation by acting as reservoirs. Aqueous suspensions of polymeric nanocapsules are directly applied on the skin or used as intermediate products for semisolid formulations, such as hydrogels and emulgels. The rheological characteristics of semisolid formulations can be modified by the presence of nanocapsules. Polymeric nanocapsules are valuable devices for skin applications and represent a promising research field in terms of providing products to be explored by industry.
Fernanda S. Poletto, Ruy C. R. Beck, Sílvia S. Guterres, Adriana R. Pohlmann

Topical Application of Nanostructures: Solid Lipid, Polymeric and Metallic Nanoparticles

Nanoparticles are currently widely used in drug delivery systems due to the possibility for sustained release and the protection of labile groups from degradation, and also because they can pass through biological barriers. Topical application of nanostructures represents a promising route mainly for the treatment of skin diseases and even for cosmetic use, such as in anti-aging formulations. Different types of nanostructures, such as solid lipid, polymeric and metallic nanoparticles, have been widely employed. Depending on the characteristics of the nanostructure, drugs or bioactives can be delivery preferentially to different skin layers. In this chapter, we describe the main methods available for the preparation and characterization of these nanostructures. Examples of topical application are described and their main advantages highlighted. These nanostructures offer a feasible approach to modulating bioactive compounds and controlling drug permeation into the skin.
Nelson Durán, Zaine Teixeira, Priscyla D. Marcato

Lipid Nanoparticles as Carriers for Cosmetic Ingredients: The First (SLN) and the Second Generation (NLC)

Colloidal carrier systems like solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) were developed with a perspective to meet industrial needs related to a simple technology involving low costs and easiness for scaling-up ensuring the process qualification and validation required for the pharmaceutical and cosmetic industries. Production methods which are suitable for large scale production, innovative applications, recent advances and technological challenges are some of the aspects which are outlined in this chapter. Appropriate analytical techniques suitable for characterizing SLN and NLC are also discussed because of their relevance for product development.
Kleber L. Guimarães, Maria Inês Ré

Industrial Production of Polymeric Nanoparticles: Alternatives and Economic Analysis

A number of studies in the last 20 years describe the development of several techniques to produce a great variety of nanoparticles applied as drug delivery systems, among them, the nanoprecipitation. However, no study analyzing the profitability of such systems was found in the literature. Therefore, in this work it is analyzed the profitability of a polymeric nanoproduct produced by the method of nanoprecipitation: the bezophenone-3, a sunscreen agent. Based on the laboratory procedures, 3 alternatives were proposed for the industrial production, including a static mixer and a ceramic membrane pre-filtration step. The simplified profitability analysis was done based on a methodology called Bare Module Cost. Its results showed that lowest sale prices were achieved when the particles are produced through the most simplified process and dividing the production in more batches per day. The procedure presented in this chapter is general and can be widely applied to other type of nanoparticles and processes.
Luciane F. Trierweiler, Jorge O. Trierweiler

Elastic Liposomes

Phospholipids type, specific molecules and production processes increase the elastic properties of the membrane, making liposomes useful for the percutaneous transport of drugs and cosmetics. Herein we describe the elastic liposomes state-of-the-art technologies, the main elastic liposome systems, the parameters that quantify the membrane elasticity, the rheology of liposomes flowing down narrow capillaries and the possible mechanisms by which the elastic liposomes transport drugs to the deeper layers of the skin. Future perspectives of the conscientious development of elastic liposomes are envisaged.
Maria Helena A. Santana, Beatriz Zanchetta

Chitosan as Stabilizer and Carrier of Natural Based Nanostructures

The use of nanotechnology in the development of cosmetics can bring new sights to old approaches. Liposomes are classic nanostructured systems largely used because of their ability to entrap hydrophilic and hydrophobic active substances. However, new materials can be obtained by the association of such classical devices with other materials, like the polyelectrolyte chitosan. In this way, chitosan can be used to modulate the surface properties of liposomes. The large surface area makes crucial the knowledge about interfacial phenomena for systems that contain nanoparticles. On the other hand, the macroscopic properties, e.g. rheology, can be modified by the association of chitosan and nanoparticles, affecting sensory attributes. Finally, on the biomedical field it is also possible to produce new devices to be used as support to growth cells employing the same strategy. By analyzing some fundamental aspects of the nanoparticles as well as their carrier it is possible to bring new and better systems based on chitosan.
Maria I. Z. Lionzo, Aline C. Dressler, Omar Mertins, Adriana R. Pohlmann, Nádya P. da Silveira

Applications of Nanocosmetics and Nanomedicines for Skin Treatments


Performance of Elastic Liposomes for Topical Treatment of Cutaneous Leishmaniasis

Non-invasive and non-toxic drugs are highly needed for the treatment of several skin diseases. Among those, local topical treatment is more desirable over oral treatment that may produce systemic side-effects. Thickening of the skin is a common feature in chronic skin diseases such as cutaneous leishmaniasis (CL). Nowadays, conventional permeation enhancers that may facilitate the drug passage through the tight stratum corneum skin barrier have been considered obsolete. Thus, appropriate delivery systems capable to carry the drug across the thickened skin are highly needed. This chapter presents an overview on the current therapy of CL and a new approach for topical treatment using conventional and pegylated liposomes as skin carrier systems for an active and highly hydrophobic antileishmanial chalcone.
Bartira Rossi-Bergmann, Camila A. B. Falcão, Beatriz Zanchetta, Maria Vitória L. Badra Bentley, Maria Helena Andrade Santana

Druggable Targets for Skin Photoaging: Potential Application of Nanocosmetics and Nanomedicine

Skin is the organ most exposed to environmental sunlight. Many in vitro and in vivo studies on skin have now unambiguously gathered evidence of the ultraviolet (UV) radiation involvement in the development of human skin pathologies such as sunburn, aging, autoimmunity, immunosuppression and cancer. Thus, the toxic effects of UV from natural sunlight and therapeutic artificial lamps are a major concern for human health. The mechanisms by which UV radiation promotes skin damage have been under intense investigation for decades, and much progress has been made in identifying the molecular alterations associated with changes in cellular functions. Furthermore, these studies are providing potential targets for molecular therapies. The aim of this chapter is to summarize the general knowledge available in the field of UV-induced skin damage, with an emphasis on the discussion of molecular markers of cellular senescence and inflammation. Besides the biological consequences of photodamage, this chapter also deals with technologies available for the detection of phototoxicity and characterization of the molecular action of nanostructures, and shows how helpful such approaches can be with a view to improving the photoprotection provided by skin products.
Giselle Z. Justo, Sílvia M. Shishido, Daisy Machado, Rodrigo A. da Silva, Carmen V. Ferreira

Nanomedicine: Potential Killing of Cancercells Using Nanoparticles

This chapter describes apoptosis as an active process of cellular deconstruction and compares it morphologically with necrosis. In contrast to necrosis, apoptosis involves the regulated action of catabolic enzymes (proteases and nucleases) within the limits of near-to-intact plasma membranes. It also involves the activation of specific caspases that cleave at specific sites after aspartic acid residues. In this context cell death by necrosis and cell death by apoptosis signaling are also discussed in this chapter. One strategy to achieve efficient drug delivery it is to understand the interactions of nanomaterials with the biological environment, targeting cell-surface receptors, drug release, multiple drug administration, stability of therapeutic agents and molecular mechanisms of cell signaling involved in the pathology of several diseases. These aspects are discussed in this chapter mainly in terms of polymeric and silver nanoparticles, in both cases with reference to in vitro and in vivo experiments. The perspectives with regard to the encapsulation of anticancer drugs in nanosystems are also discussed. All of the information available to date indicates that nanomedicine will play a crucial role in cancer treatment.
Patricia da Silva Melo, Priscyla D. Marcato, Nelson Durán

Zebrafish as a Suitable Model for Evaluating Nanocosmetics and Nanomedicines

The assessment of complex in vivo phenotypes using the teleost zebrafish provides an alternative tool to combine detailed toxicological studies with the large-scale screening of chemicals. The zebrafish, Danio rerio, represents a versatile model organism with many molecular, morphological, and physiological similarities to mammals. It is well suited for studies in genetics, embryology, development, and cell biology, and, in recent years, it has become an important vertebrate model for small molecule studies. Several characteristics contribute to the growing interest in this tropical fish for high-throughput screening such as its small size, high reproductive capacity, accessibility for genetic manipulation, optical transparency which allows visual assessment of developing cells and organs, suitability for treatment by water exposure, low maintenance costs, and a large and growing biological database. In the present chapter, we outline the use of the zebrafish in biomaterial nanotoxicity studies and the potential of this model for the phenotype-based screening of skin care products.
Carmen V. Ferreira, Maria A. Sartori-da-Silva, Giselle Z. Justo

Nitric Oxide-Releasing Nanomaterials and Skin Care

The gaseous free radical nitric oxide (NO) is a key endogenous found molecule involved in several physiological and pathophysiological processes in different organs and tissues. NO is synthesized by several cell types in the human skin, where regulates diverse homeostatic functions, such as the control of dermal blood flow, the promotion of wound healing, the skin pigmentation, and the anti-aging effects. Due to its unique chemistry structure and biological versatility, NO is also an important mediator of diverse human skin diseases, and plays a defense role against skin pathogens. Therefore, there is an explosive interest on the development of biological friendly vehicles for topical NO release in several dermatological applications. In this scenario, the preparation of NO-releasing nanomaterials, as controllable NO dispenser, is a promising strategy for diverse applications in human skin, as discussed in this chapter.
Amedea B. Seabra

Nanocarriers and Cancer Therapy: Approaches to Topical and Transdermal Delivery

The main goals of nanotechnology in cancer are to develop safer and more effective diagnostics and therapeutics. Nanotechnology can bring advantages to drug delivery, overcoming the limitations of conventional formulations. Drugs encapsulated in targeted nanocarriers are promising for the improvement of efficacy and safety of not only currently available drugs, but also certain chemical or biological compounds that were not previously used due to toxic effects or because they were not able to be administered. Drug delivery across the skin is an extremely attractive route due to the possibility of targeting skin diseases (topical), for achieving systemic effects (transdermal administration), providing patient convenience, and avoiding first-pass hepatic metabolism. However, this route still remains a challenge due the highly organised stratum corneum structure. Several strategies have been studied to optimize topical and transdermal drug delivery, including physical techniques, such as eletroporation and iontophoresis, and nanotechnology-based drug delivery systems. This work discusses nanotechnology evolution and the use of several nanotechnology strategies to increase skin penetration and permeation in the improvement of cancer treatment.
Juliana M. Marchetti, Marina C. de Souza, Samantha S. Marotta-Oliveira

Nanocarriers to Deliver Photosensitizers in Topical Photodynamic Therapy and Photodiagnostics

Topical photodynamic therapy is used for the prevention and treatment of non-melanoma skin cancer. Until recently, clinically approved indications have been restricted to superficial basal cell carcinoma and nodular, actinic keratoses and, since 2006, Bowen’s disease. Most photosensitizers are relatively hydrophobic and will be attracted to membranes, but even the exception molecules, having substituents that render them watersoluble, bind to membranes because of their hydrophobic ring systems. The primary function of the skin, however, is to protect the body from unwanted influences from the environment. This protection is provided primarily by the stratum corneum, which consists of corneocytes surrounded by lipid regions. The major limitation of PDT is the poor penetration of photosensitizers through biological barriers, like the skin. Over the past 10 years, a considerable number of studies have therefore been conducted on the development of different strategies to overcome these difficulties, including nanocarriers to delivery photosensitizers and their precursors, nanoemulsions, liposomes, ethosomes, invasomes, liquid crystals and magnetic nanoparticles, among others.
Wanessa S. G. Medina, Fabíola S. G. Praça, Aline R. H. Carollo, Maria Vitória L. Badra Bentley

Production of Nanofibers by Electrospinning Technology: Overview and Application in Cosmetics

This chapter relates to the techniques to produce polymer nanofibers and specifically discusses one of those techniques which has been recently investigated, namely Electrospinning. An overview of this technology is described, considering the work trend based on nanofiber and electrospinning publication in scientific paper and patents. Moreover, issues regarding the main process control parameters, applications of polymer nanofibers and the appropriate characterization of these nanofibers or mats are presented. Applications in cosmetic field are outlined, as well as the future perspective of the electrospinning technology in cosmetic application.
Maria Helena A. Zanin, Natalia N. P. Cerize, Adriano M. de Oliveira

Nanosized and Nanoencapsulated Sunscreens

Nanotechnology represents an important complement to traditional chromophore-based UV filters. Nanosized metal oxides are widely used due to their broad protection spectrum and reduced skin irritation. These particles are already present in most commercial sunscreen lotions even though their photoreactivity has been highlighted as a potential cause of cytotoxic effects in human skin cells (e.g. fibroblasts, epithelial cells). However, this cytotoxicity is not likely to represent a significant health risk to consumers as several skin penetration assays have shown that the photoreactive particles penetrate at most to the stratum spinosum of the epidermis. Nanoencapsulation of traditional organic UV filters is a more recent approach to improve skin retention, photostability and the UV blocking ability of the free molecules. All of these improvements have been confirmed with different scientific assays for different particles, especially polymeric nanocapsules and solid lipid nanoparticles. These technological advantages offered by nanometric particles for sun protection formulations have made them commercially important. In inventories from non-governmental organizations there are approximately 30 commercial sunscreen products listed as containing nanoparticles.
Cássia B. Detoni, Karina Paese, Ruy C. R. Beck, Adriana R. Pohlmann, Sílvia S. Guterres


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