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Posted: Mar 13, 2013
Nanodermatology Society summarizes results of its recent annual meeting
(Nanowerk News) The Nanodermatology Society (NDS) recently held its 3rd annual meeting, in conjunction with the 71st meeting of the American Academy of Dermatology, at the Loews Miami Beach Hotel, on March 3, 2013. Clinicians, scientists, and members of industry from around the globe met in person to present their research, integrate their knowledge, and develop partnerships for future collaborations. The program included 6 presentations from leading experts in dermatology and Nanodermatology, and covered a broad range of subjects, including: the human skin biome, the long term toxicity of nanoparticles from chronic exposure, cutaneous penetration of nanomaterials along the hair follicle, the effect of metal nanoparticles on the skin, and the potential of nanomaterials for the development of topically delivered vaccines and anti-pruritic therapies.
Dr. Adam Friedman, Vice President of the Nanodermatology Society and Director of Dermatologic Research at the Albert Einstein College of Medicine, commenced the meeting by illustrating how this has been a “gargantuan” year for nanodermatology. He then underscored some of the highlights in Nanodermatology for 2012, including the publication of the textbook “Nanotechnology in Dermatology”, the use of spherical nanoparticle nucleic acid conjugates to suppress different genes in the skin, the development of heavy chain human ferritin based nanoplatforms for melanoma targeting, and the use of antimicrobial and anti-inflammatory chitosan alginate nanoparticles for the treatment of acne. Dr. Friedman also discussed how the NDS has responded to recent overtures by the US Food and Drug Administration’s new draft guidelines on the use of nanotechnology in food and cosmetics. He stated that the position of the NDS is in agreement with that of the AAD: that the main benefits of nanoparticles in sunscreens outweighs any potential dangers at this time, and to date, all research shows that the stratum corneum is an effective barrier to prevent entry of nanoparticles into the deeper layers of the skin. Dr. Friedman stated that there is still no “official” definition of “nanotechnology” at the FDA, stressing the continued importance of the NDS to provide education to dermatologists and the general public not familiar with nanotechnology.
Dr. Michael Wilkerson (University of Texas) discussed some of the emerging safety concerns for nanotechnology, focusing on the long term effects of titanium dioxide (TiO2) exposure. Dr. Wilkerson began, by stating “Titanium dioxide is the largest industrial produced nanoparticle in the world, with typical industrial production down to 25 nm.” Nanoparticles (NP’s) are found throughout nature, during combustion reactions, in volcanic eruptions, erosion, and people are naturally exposed to NP’s all the time. There is therefore a natural adaptation and tolerance to NP’s that is imperative for survival. He continued, saying, “The people at greatest risk for development of possible toxicity to nanoparticles are those who work with them, both in industry and in the laboratory.” He reviewed how the physical properties of TiO2 change when it is reduced to a smaller size. In larger sizes, TiO2 is an inert material, but when reduced to a smaller size, it becomes highly photoreactive, and can produce singlet oxygen (ROS). Studying the toxic effects of exposure to nanomaterials is challenging, because once compounded, it is very difficult to keep materials <100 nm due to attractive forces between molecules. Dr. Wilkerson explained that most studies concerning nanoparticle toxicity examine acute exposure and subsequent toxicity. However, most real world exposure to nanomaterials is chronic. The potential for nanomaterials to gradually accumulate in tissue over a long period of time is the most concerning. He showed that Chinese Hamster Ovary cells (CHO) have a concentration dependent increase in ROS in both acute and chronic TiO2 exposed cells. Over time, the effect of TiO2 diminishes in chronically exposed cells. Overall, however, CHO cells appear to adapt to chronic exposure of nano TiO2 and detoxify excess ROS by up regulation of SOD and possibly reducing particle uptake, indicating the presence of inherent defense and compensatory mechanisms. Furthermore, Dr. Wilkerson stated that the effect of TiO2 on cells seems to be minimal without light.
Dr. Heidi Kong (NIH) discussed her work on the Human Microbiome Project, and how it is important to characterize and understand the bacteria that live on the skin. Genomic analysis of skin swabs across 20 distinct skin sites spread across sebaceous, moist, and dry microenvironments revealed far greater diversity than culture based methods had ever shown. There were 112,283 16S gene sequences extracted from patient samples, which identified 19 bacterial phyla. After developing a comprehensive baseline of normal skin across a variety of different sites, Dr. Kong looked at how the skin microbiome of patients with atopic dermatitis changes at baseline, during flares, and post treatment improvement. During flares, baseline levels of S. aureus climbed steeply, sometimes 1000 fold. S. epidermidis also increased sharply. Microbial diversity dropped dramatically. Without nanotechnology, this type of high throughput and sensitive analysis of genes would not be possible.
Though she was unable to present, Dr. Zoe Diana Draelos, from the Duke University School of medicine, was scheduled to discuss some of the possibilities for nanoparticle metals. Nanometals have been studied since they were first described by Michael Faraday in 1857. Nanometals currently known to be important for skin health and function include selenium, copper, zinc, magnesium, and iron. Selenium is an important antioxidant for the skin, and protects the skin through involvement with glutathione peroxidase and thioredoxin reductase. Selenium sulfide is used in rinse of products such as dandruff shampoos. Copper is commonly found in wound healing and anti-aging products, and possesses antimicrobial and antiviral activities. Copper containing pillowcases have been found to reduce wrinkling by stimulating extracellular matrix protein production. 11% of the zinc in the body resides in the epidermis, and zinc compounds are used in dandruff shampoos, antifungals, and sunscreens. Metal nanoparticles are used in both cosmetics and potential cosmeceuticals. The high surface area to volume ratio of nanoparticles creates an increased driving force for diffusion across the skin barrier. Their small size confers the benefit of invisibility, as these nanoparticles are 4-7 times smaller than the visible wavelength of light. These metal nanoparticle cosmeceuticals can potentially deliver metals necessary for wound healing and collagen remodeling to potential benefit.
Anna Vogt (Charité-University Medicine Berlin, Germany) discussed how nanoparticles preferentially enter the skin through hair follicle openings. Particles of <200 nm including polystyrene, gold, silver, silica, viruses, virus like particles, and DNA, can all be used to target specific cell populations within the hair follicle. Using fluorescence microscopy, X-ray microscopy, confocal microscopy, and flow cytometry, Dr. Vogt demonstrated that there are populations of Langerhans cells (using anti-CD1a) within the hair follicle. Nanoparticles that become trapped in the hair follicle provide Langerhans cells with enough time, and a reservoir of particles for significant interaction. Nanoparticles can then be transported to proximal and distal lymph nodes. This mechanism can be used for particle based peptide delivery in transcutaneous vaccination, and there are currently 2 ongoing clinical trials. Biodegradable poly-lactic-acid particles, are nanoparticles that can be used for the barrier translocation of nanomaterials. Dr. Vogt described how the stability and penetration of these nanoparticles depends on their molecular load. This opens the door to “smart” dermatotherapies; products that only target specific areas of the skin with fewer side effects.
Dr. Gil Yosipovitch (Wake Forest University School of Medicine, NC), known by many as the “Godfather of itch”, discussed some of the future perspectives of nanotherapuetics for the treatment of chronic itch. He was particularly excited by the research presented by Dr. Anna Vogt, explaining that if there is a reservoir of nanoparticles that collect along the hair follicle it would hold enormous potential for the treatment of chronic itch. Dr. Yosipovitch explained that nerve fibers in the epidermis and epidermal-dermal junction (DEJ) are overactive in patients with chronic itch, and the hair follicle is an important target for anti-itch medication. The development of ultra-small polymer particles that allow for the controlled release of anti-pruritics would enable targeted drug therapy focused on the epidermis, DEJ skin and nerve fibers. Dr. Yosipovitch described many potential targets along the hair follicle, from the infundibulum (CB1, CB2, and NK1) to the hair bulb (CB2, TRPV1, NK1, B-endorphin) and dermal papilla (SP, CGRP, MOR). Sensitization to itch is associated with nerve growth factors, including G-protein coupled receptors, and ion channel receptors. The stratum corneum is in close proximity to fibers containing these receptors. As Dr. Yosipovitch elegantly stated, “If you remove the upper layers of skin, you don’t have itch, you only have pain.” Because topical nano-therapeutics concentrate in the upper layers of the skin, nanotechnology offers potential for the treatment of itch. Future perspectives of nanodermatology therapies for itch include the development of ultra-small polymers that allow controlled release of anti-pruritics, as well as combination drugs that make possible precise feedback mechanisms that can safely regulate the release of drugs on board nanoparticles to maximize activity, while minimizing toxicity.
Nanotechnology is being utilized and researched worldwide, and it will continue to be a major target of investigation by both private corporations and academic researchers. The collaboration between industry and academia through the Nanodermatology Society offers great potential for both translational and basic research collaborations. The NDS is a forum where scientists from different countries and settings can meet and develop relationships that involve exchanges among researchers in a field where geography and scientific research have no barriers, providing greater chances of success.