Nanodermatology: Summary from the Second Annual International Conference the Nanodermatology Society

Nanodermatology is a relatively new branch of engineering that is making rapid inroads in both the diagnosis and treatment of dermatologic disease. Nanotechnology applies the unique properties of matter on the nanoscale for the purposeful design of new materials. Among US patent holders in nanotechnology, the sixth largest is a cosmetics company, which comes as no surprise as this science can be used to enhance topical delivery of a broad range of consumer products. Concerns regarding incidental exposure to nanomaterials and the potential associated toxicity have generated considerable interest in determining the extent to which nanoparticles may penetrate skin as well as under what conditions - key properties for both efficacy and toxicity. Work by investigators to date highlight that the positive benefit of engineered nanoparticles for use in cosmetics and as tools for understanding skin biology and curing skin disease outweigh potential toxicity concerns.

At the second international conference of the Nanodermatology Society (NDS) clinicians, scientists, members of industry, and policy makers gathered in San Diego, California on March 16th 2012 to review and discuss recent advances in nanotechnology and potential pitfalls as they pertain to dermatology. The conference was held at the Manchester Grand Hyatt in conjunction with the 70th Annual Meeting of the American Academy of Dermatology. The program included six presentations by leading experts in dermatology and nanodermatology, and covered a broad range of subjects including: updates in photoprotection, nano-needle drug delivery, cutaneous penetration of nanomaterials, nano-encapsulation of acne therapeutics, and siRNA conjugated nanoparticles for the treatment of skin disease.

Dr. Adam Friedman kicks off the meeting by emphasizing how important education is in changing attitudes toward nanotechnology.

Dr. Adam Friedman, Vice President of the Nanodermatology Society and Director of Dermatologic Research at the Albert Einstein College of Medicine called the meeting to order by illustrating how "nanodermatology" has recently become part of the dermatology lexicon, having infiltrated mainstream dermatology media and high level publications such as the Journal of Investigative Dermatology. He then reviewed highlights in nanodermatology from 2011, including the use of calcium phosphate nanoparticles as a means to prevent nickel ion skin penetration to combat nickel contact dermatitis as well as the advent of laser induced biological nanosutures for cutaneous surgery closure. Dr Friedman stressed the importance of providing education to dermatologist on the field of nanotechnology, reviewing results from a recent survey based study demonstrating that over 70% of the participants were not familiar with nanodermatology but were very interested to learn more and recognized its growing importance to the field of dermatology.

Dr. Henry Lim keeps us abreast of the US FDA's upcoming rules and regulations on sunscreen.

Dr. Henry Lim (Henry Ford Hospital, MI) provided a brief overview of the recent developments in sunscreen rules and regulation by the US FDA. He began the talk by discussing the "final rule" issued by the FDA in 2011 regarding labeling and testing of sunscreens. The final rule comprised issues such as SPF abbreviation, broad-spectrum statement and testing methodology, water resistance statement, and sunscreen application directions. The ruling also validated the protective role of sunscreen in preventing skin cancer and skin aging when used appropriately with other photoprotective measures (sunglasses, hats, etc.). The final rule, once enforced, will provide US consumers a means to gauge the degree of UVA protection in the products. Dr. Lim pointed out that although this final rule has now been approved and published, because of other unresolved issues (for example, dosage forms of sunscreen) the FDA sunscreen monograph is not yet considered to be final at this time. Another focus of the talk was the latest developments in the field of sunscreen technology. During this part of his presentation, Dr. Lim discussed the generation of photostable UV filters, the published studies regarding systemic photoprotection, and the new technologies to minimize concentration of UV filters and to develop better antioxidant formulations.

Dr. Bai Xu directly compares the scale of a conventional needle to that of a microneedle array.

Dr. Bai Xu (Nanomed Skincare, Inc, NY) detailed the construction of microneedles and their epicutaneous applications. Using lithographic techniques inspired by the semiconductor industry, Dr. Xu and his colleagues etched and deposited an array of microneedles on a silicon wafer. At 120 µm in length, the needles perforate the stratum corneum allowing large molecules access to the lower layers of the epidermis and the dermis. In addition to allowing large molecules into the skin, the microneedle array also affects the rate of drug absorbance. For example, when a low cost but fast acting insulin analog is delivered transcutaneously with the microneedle system, it takes on the biophysical profile of subcutaneously delivered long acting insulin. With the potential to be used with almost any medication, initial investigations have already shown the benefit of the microneedle system for the treatment of acne and the delivery of local anesthetics. Questions focused on the failure rate and safety of the device. Dr. Xu responded by explaining that the device applies a specified amount of force onto the microneedle array and confirms a successful application with an indicator light.

Dr. Nancy A. Monteiro-Riviere (North Carolina State University, NC) discussed skin penetration of nanomaterials, an important topic both for patients treated with nanomaterials as well as researchers handling them. Nanomaterials are readily taken up by keratinocytes through scavenger receptor and low density lipoprotein receptor related pathways. It is well established that nanoparticle size affects penetration. Using fluorescently labeled fullerenes, Dr. Monteiro-Riviere demonstrated that the coating, shape and delivery vehicle of a nanoparticle affects skin penetration, systemic absorption and immune activation. Her more recent investigation focuses on host factors that influence nanomaterial penetration. Both repetitive flexing and skin abrasion did increase penetration of fullerenes. The penetration of titanium dioxide (TiO2) and zinc oxide (ZnO) sunscreens was shown to be minimal on normal skin. Penetration of the TiO2 slightly increased following UVB induced sunburns, though no change was noted with the ZnO treated skin. Pretreatment of the skin with water and alcohols did not increase penetration, though this was send with cyclohexane pretreatment. Finally, Dr. Monteiro-Riviere shared some of the unforeseen hazards of nanomaterial research, including the discovery of formaldehyde in a stock nanoparticle she was using for a toxicity assay and the realization that the discordant results of a penetration study conducted in her lab and at the FDA's was due to the age of the pigs (and the older pigs larger follicular ostia).

Dr. Tarl Prow (University of Queensland, Australia) discussed his work on tracking nanoparticles in human skin using non-invasive imaging, mainly focusing on the fluorescence lifetime imaging microscopy (FLIM). To date, there has been a lack of highly effective techniques to assess nanoparticle penetration and its biological effects in human studies. Dr. Prow reviewed his work with FLIM to simultaneously determine zinc oxide nanoparticles (ZnO-NP) penetration profiles and metabolic state (via NAD(P)H changes). His work enabled these determinations in nonlesional skin as well as in subjects with altered barrier function (including tape-stripped skin and in psoriasis or atopic dermatitis lesions) making it highly clinically relevant. It was found that there was increased ZnO-NP signal within the stratum corneum of disrupted and lesional skin, but the ZnO-NP did not penetrate into viable human epidermis in any of the studied groups. Dr. Prow also reported that there was no consistent ZnO induced NAD(P)H effects on lesional or non-lesional skin. He concluded that FLIM has the potential to non-invasively evaluate the potential exposure and metabolic consequences of nanoparticle-containing topical products in human subjects.

Dr. Sam Shefer (Salvona Technologies, NJ) spoke about encapsulation systems developed by his company, which are able to alter the bioavailability, release kinetics, tissue selectivity, shelf life and toxicity of incorporated drugs. Food grade materials are used to make 100-200 nanometer spheres that can then be encapsulated again within a larger 15 to 30 micron sphere. By varying the hydrophobicity, acidity and surface coatings of the spheres, the biochemical characteristics of a wide variety of molecules can be tuned for optimal delivery. Dr. Shefer outlined his strategies for encapsulating acne medication, male pattern baldness medication, anti-inflammatories and antifungals.

Dr. Amy Paller (Northwestern University, IL) presented her work on topical delivery of siRNAgold nanoparticle conjugates. siRNA has been shown to be involved in the RNA interference (RNAi) pathway, where it interferes and down-regulates the expression of a specific gene of interest. Because some skin disease processes also depend on the activity of multiple genes, it is expected that in those situations turning off the activity of a specific gene(s) using siRNA could produce therapeutic benefit. However, the major challenge in this field has been delivery of siRNA through the epidermal barrier and into cells in sufficient concentration to knock down gene expression. To overcome this challenge, Dr. Paller's research has focused on siRNA delivery using gold nanoparticles. Her results showed ~100% uptake of the siRNA conjugated nanoparticles in cultured keratinocyte, and excellent uptake through the epidermal barrier of mouse skin when topically applied. The high uptake led to more efficient and persistent gene knockdown in skin. She also noted that these nanoparticles showed no apparent toxicity in vivo. Potential application of this delivery system includes knockdown through topical application of Ras-mediated epidermal hyperplasia, metastatic melanoma, diabetes, and genetic skin disorders.

Sponsorship for the meeting/society was provided by Nanomed Skincare, Merck, Schering-Plough, Johnson & Johnson, Horiba Scientific, P&G, and BASF Fonte: Nanowerk _____________________________ Vejam: a) The Second Annual International Conference the Nanodermatology Societyf b) New Study Finds That Nanotechnology Education is Lacking in Dermatology Training but Dermatologists are Eager to Learn More