Acne Causing Bacteria Killed By Nitric Oxide Generated From Nanoparticles

Adam Friedman, MD, FAADAssociate Professor of Dermatology Residency Program Director Director of Translational Research Department of Dermatology George Washington School of Medicine and Health ScienceMedicalResearch.com Interview with:
Adam Friedman, MD, FAAD
Associate Professor of Dermatology
Residency Program Director
Director of Translational Research
Department of Dermatology
George Washington School of Medicine and Health Sciences

Medical Research: What is the background for this study? What are the main findings?

Dr. Friedman: Acne vulgaris is one of the most  common skin disease that affects approximately 40-50 million people in the United States.    Acne’s multifactorial etiology, resulting from a mix of androgen-induced elevations in sebum production, abnormal follicular epithelial desquamation and proliferation, hypercolonization of Propionibacterium acnes and host inflammatory reactions, make treatment often times challenging. In looking at the topical therapeutic armament for Acne Vulgaris, which includes benzoyl peroxide, salicyclic acid, topical antibiotics such as clindamycin, and retinoids, all suffer from various related side effects including irritation, erythema, dryness, peeling and scaling, bacterial resistance, and resulting dyschromia from the associated irritation in patients of darker skin types. These adverse events often serve as major limiting factors influencing patient compliance and ultimately impacting efficacy. Therefore new treatments which target all of the complexities of acne are needed, especially given we have not had anything really new brought to market in years. Here, we looked to biology for the answer. Our bodies generate Nitric Oxide, a diatomic lipid loving gaseous molecule, to perform a broad range of biological activities, including but not limited to killing bacteria/fungi/viruses  and inhibiting inflammation – key elements in Acne. Its action however is very short lived and therefore using Nitric Oxide as a treatment is difficult as one would need a delivery system that would allow for continued and controlled release. Enter nanotechnology. We designed exceedingly small particles (of note, 1 nanometer = 1 billionth of a meter) which allow for the generation of nitric oxide gas from nitrite salt, and will only release the gas when exposed to moisture over time. The size of the particles also enables them to better interact with their environment, i.e. cells, pathogens, improving their activity as compared to large sized treatments

In this study, we showed that the nitric oxide generating/releasing nano particles effectively killed the organism, P. acnes but was not toxic to both human skin cells and a live vertebrae model (embryonic zebra fish). More importantly, we found that the nano particles inhibits the activation of a newly recognized but exceedingly important inflammatory pathway that is directly tied to the formation of an acne lesion, called the NLRP3 inflammasome. Research has shown that our bodies already regulate this pathway with nitric oxide, and therefore once again, we are looking to biology for answers. As opposed to a drug that may only have one target, the nanoparticles inhibited multiple components/elements of the inflammasome pathway, giving some insight into its potential as a treatment for acne as well as other inflammatory diseases.

Medical Research: What should clinicians and patients take away from your report?

Dr. Friedman I think one theme of this paper is targeted medicine: Elucidating the the underpinnings of disease, correlating  with normal physiology, and creating a therapy based on this understanding. This has been the modern template for many new therapies for a broad range of diseases from cancer to psoriasis. Having a strong grasp on the biology allows the practitioner to both use medication off label based on their mechanism as well as help guide the development of new therapies. Focusing more on the paper, I think a broader appreciation of nanotechnology, specifically nanomedicine is important as there is limitless potential to both improve the sustainability and efficacy of established medications and  allow for the delivery of unstable or previously undeliverable agents like nitric oxide.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Friedman: The next steps for this research is clinical trials. There are currently no great animal models for acne so very often once the standard quality assurance and safety studies are complete, one can enter the clinical space. We are currently working towards commercializing this technology through a company named Nano BioMed inc, and hope to move this into the clinical space with great speed.

In terms of broader future research initiatives, a better understanding of how or if  both old and new drugs effect the inflammasome pathway is an important step in the right direction as this is clearly an important target.

Citation:

Nitric Oxide Releasing Nanoparticles Prevent Propionibacterium acnes Induced Inflammation by both Clearing the Organism and Inhibiting Microbial Stimulation of the Innate Immune Response.

Min Qin1, Angelo Landriscina2, Jamie Rosen2, Gabrielle Wei1, Stephanie Kao1, William Olcott1, George W Agak1, Karin Blecher Paz2, Josephine Bonventre3, Alicea Clendaniel3, Stacey Harper3,4, Brandon Adler2, Aimee Krausz2, Joel Friedman5, Joshua Nosanchuk6,7, Jenny Kim1,8 and Adam J Friedman2,5,9

Journal of Investigative Dermatology accepted article preview 14 July 2015; doi: 10.1038/jid.2015.277

Adam Friedman, MD, FAAD (2015). Acne Causing Bacteria Killed By Nitric Oxide Generated From Nanoparticles 

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