Posted: May 7th, 2012 Summary from the Second Annual International Conference theNanodermatology Society ( Nanowerk News ) Nanodermatology is a relatively new branch of engineering that ismaking rapid inroads in both the diagnosis and treatment ofdermatologic disease. Nanotechnology applies the unique propertiesof matter on the nanoscale for the purposeful design of newmaterials. Among US patent holders in nanotechnology, the sixthlargest is a cosmetics company, which comes as no surprise as thisscience can be used to enhance topical delivery of a broad range ofconsumer products. Concerns regarding incidental exposure tonanomaterials and the potential associated toxicity have generatedconsiderable interest in determining the extent to whichnanoparticles may penetrate skin as well as under what conditions -key properties for both efficacy and toxicity. Work byinvestigators to date highlight that the positive benefit ofengineered nanoparticles for use in cosmetics and as tools forunderstanding skin biology and curing skin disease outweighpotential toxicity concerns.
At the second international conference of the Nanodermatology Society (NDS) clinicians, scientists, members of industry, and policymakers gathered in San Diego, California on March 16th 2012 toreview and discuss recent advances in nanotechnology and potentialpitfalls as they pertain to dermatology. The conference was held atthe Manchester Grand Hyatt in conjunction with the 70th AnnualMeeting of the American Academy of Dermatology. The programincluded six presentations by leading experts in dermatology andnanodermatology, and covered a broad range of subjects including:updates in photoprotection, nano-needle drug delivery, cutaneouspenetration of nanomaterials, nano-encapsulation of acnetherapeutics, and siRNA conjugated nanoparticles for the treatmentof skin disease. Dr. Adam Friedman kicks off the meeting by emphasizing howimportant education is in changing attitudes toward nanotechnology.
Dr. Adam Friedman, Vice President of the Nanodermatology Societyand Director of Dermatologic Research at the Albert EinsteinCollege of Medicine called the meeting to order by illustrating how”nanodermatology” has recently become part of the dermatologylexicon, having infiltrated mainstream dermatology media and highlevel publications such as the Journal of InvestigativeDermatology. He then reviewed highlights in nanodermatology from2011, including the use of calcium phosphate nanoparticles as ameans to prevent nickel ion skin penetration to combat nickelcontact dermatitis as well as the advent of laser inducedbiological nanosutures for cutaneous surgery closure. Dr Friedmanstressed the importance of providing education to dermatologist onthe field of nanotechnology, reviewing results from a recent surveybased study demonstrating that over 70% of the participants werenot familiar with nanodermatology but were very interested to learnmore and recognized its growing importance to the field ofdermatology. Water Playground Equipment
Dr. Henry Lim keeps us abreast of the US FDA’s upcoming rules andregulations on sunscreen. Dr. Henry Lim (Henry Ford Hospital, MI) provided a brief overviewof the recent developments in sunscreen rules and regulation by theUS FDA. He began the talk by discussing the “final rule” issued bythe FDA in 2011 regarding labeling and testing of sunscreens. Aquasplash Water Park
Thefinal rule comprised issues such as SPF abbreviation,broad-spectrum statement and testing methodology, water resistancestatement, and sunscreen application directions. The ruling alsovalidated the protective role of sunscreen in preventing skincancer and skin aging when used appropriately with otherphotoprotective measures (sunglasses, hats, etc.). The final rule,once enforced, will provide US consumers a means to gauge thedegree of UVA protection in the products. Dr. Lim pointed out thatalthough this final rule has now been approved and published,because of other unresolved issues (for example, dosage forms ofsunscreen) the FDA sunscreen monograph is not yet considered to befinal at this time. Water Sprayground Manufacturer
Another focus of the talk was the latestdevelopments in the field of sunscreen technology. During this partof his presentation, Dr. Lim discussed the generation ofphotostable UV filters, the published studies regarding systemicphotoprotection, and the new technologies to minimize concentrationof UV filters and to develop better antioxidant formulations. Dr. Bai Xu directly compares the scale of a conventional needle tothat of a microneedle array.
Dr. Bai Xu (Nanomed Skincare, Inc, NY) detailed the construction ofmicroneedles and their epicutaneous applications. Usinglithographic techniques inspired by the semiconductor industry, Dr.Xu and his colleagues etched and deposited an array of microneedleson a silicon wafer. At 120 in length, the needles perforate thestratum corneum allowing large molecules access to the lower layersof the epidermis and the dermis.
In addition to allowing largemolecules into the skin, the microneedle array also affects therate of drug absorbance. For example, when a low cost but fastacting insulin analog is delivered transcutaneously with themicroneedle system, it takes on the biophysical profile ofsubcutaneously delivered long acting insulin. With the potential tobe used with almost any medication, initial investigations havealready shown the benefit of the microneedle system for thetreatment of acne and the delivery of local anesthetics. Questionsfocused on the failure rate and safety of the device. Dr.
Xuresponded by explaining that the device applies a specified amountof force onto the microneedle array and confirms a successfulapplication with an indicator light. Dr. Nancy A. Monteiro-Riviere (North Carolina State University, NC)discussed skin penetration of nanomaterials, an important topicboth for patients treated with nanomaterials as well as researchershandling them. Nanomaterials are readily taken up by keratinocytesthrough scavenger receptor and low density lipoprotein receptorrelated pathways.
It is well established that nanoparticle sizeaffects penetration. Using fluorescently labeled fullerenes, Dr.Monteiro-Riviere demonstrated that the coating, shape and deliveryvehicle of a nanoparticle affects skin penetration, systemicabsorption and immune activation. Her more recent investigationfocuses on host factors that influence nanomaterial penetration.Both repetitive flexing and skin abrasion did increase penetrationof fullerenes. The penetration of titanium dioxide (TiO2) and zincoxide (ZnO) sunscreens was shown to be minimal on normal skin.Penetration of the TiO2 slightly increased following UVB inducedsunburns, though no change was noted with the ZnO treated skin.Pretreatment of the skin with water and alcohols did not increasepenetration, though this was send with cyclohexane pretreatment.Finally, Dr. Monteiro-Riviere shared some of the unforeseen hazardsof nanomaterial research, including the discovery of formaldehydein a stock nanoparticle she was using for a toxicity assay and therealization that the discordant results of a penetration studyconducted in her lab and at the FDA’s was due to the age of thepigs (and the older pigs larger follicular ostia).
Dr. Tarl Prow (University of Queensland, Australia) discussed hiswork on tracking nanoparticles in human skin using non-invasiveimaging, mainly focusing on the fluorescence lifetime imagingmicroscopy (FLIM). To date, there has been a lack of highlyeffective techniques to assess nanoparticle penetration and itsbiological effects in human studies. Dr. Prow reviewed his workwith FLIM to simultaneously determine zinc oxide nanoparticles(ZnO-NP) penetration profiles and metabolic state (via NAD(P)Hchanges).
His work enabled these determinations in nonlesional skinas well as in subjects with altered barrier function (includingtape-stripped skin and in psoriasis or atopic dermatitis lesions)making it highly clinically relevant. It was found that there wasincreased ZnO-NP signal within the stratum corneum of disrupted andlesional skin, but the ZnO-NP did not penetrate into viable humanepidermis in any of the studied groups. Dr. Prow also reported thatthere was no consistent ZnO induced NAD(P)H effects on lesional ornon-lesional skin. He concluded that FLIM has the potential tonon-invasively evaluate the potential exposure and metabolicconsequences of nanoparticle-containing topical products in humansubjects.
Dr. Sam Shefer (Salvona Technologies, NJ) spoke about encapsulationsystems developed by his company, which are able to alter thebioavailability, release kinetics, tissue selectivity, shelf lifeand toxicity of incorporated drugs. Food grade materials are usedto make 100-200 nanometer spheres that can then be encapsulatedagain within a larger 15 to 30 micron sphere. By varying thehydrophobicity, acidity and surface coatings of the spheres, thebiochemical characteristics of a wide variety of molecules can betuned for optimal delivery.
Dr. Shefer outlined his strategies forencapsulating acne medication, male pattern baldness medication,anti-inflammatories and antifungals. Dr. Amy Paller (Northwestern University, IL) presented her work ontopical delivery of siRNAgold nanoparticle conjugates.
siRNA hasbeen shown to be involved in the RNA interference (RNAi) pathway,where it interferes and down-regulates the expression of a specificgene of interest. Because some skin disease processes also dependon the activity of multiple genes, it is expected that in thosesituations turning off the activity of a specific gene(s) usingsiRNA could produce therapeutic benefit. However, the majorchallenge in this field has been delivery of siRNA through theepidermal barrier and into cells in sufficient concentration toknock down gene expression. To overcome this challenge, Dr.Paller’s research has focused on siRNA delivery using goldnanoparticles. Her results showed ~100% uptake of the siRNAconjugated nanoparticles in cultured keratinocyte, and excellentuptake through the epidermal barrier of mouse skin when topicallyapplied.
The high uptake led to more efficient and persistent geneknockdown in skin. She also noted that these nanoparticles showedno apparent toxicity in vivo. Potential application of thisdelivery system includes knockdown through topical application ofRas-mediated epidermal hyperplasia, metastatic melanoma, diabetes,and genetic skin disorders. Sponsorship for the meeting/society was provided by NanomedSkincare, Merck, Schering-Plough, Johnson & Johnson, HoribaScientific, P&G, and BASF.