Tag Archives: Adam Friedman

Nanotechnology tackles nail fungus

I never thought I’d be highlighting nail fungus here but sometimes life throws you a twist and a turn. Researchers at George Washington University (GWU; Washington, DC, US) announce their latest nanotechnology-enabled approach to nail fungus in a July 11, 2018 news item on ScienceDaily,

Onychomycosis, a nail fungus that causes nail disfigurement, pain, and increased risk of soft tissue infection, impacts millions of people worldwide. There are several topical antifungal treatments currently available; however, treatment failure remains high due to a number of factors.

The most recent treatment, a broad spectrum triazole called efinaconazole, is designed to improve nail penetration. It boasts the highest cure rates among other topical antifungals, but the cost for a bottle is more than $600, and full treatment calls for multiple bottles.

A July 11, 2018 GWU news release (also on EurekAlert), which originated the news item, provides more details,

Adam Friedman, MD (link is external), professor of dermatology at the George Washington University School of Medicine and Health Sciences, and his team investigated the use of nanotechnology to improve efinaconazole treatment and make it more cost effective. They observed that when nitric oxide-releasing nanoparticles are combined with the efinaconazole, it achieves the same antifungal effects, but at a fraction of the amount of the medication alone needed to impart the same effect.

“Nanotechnology is being studied and employed in many areas of medicine and surgery to better deliver established imaging and therapeutic agents to ultimately improve patient outcomes,” said Friedman. “A quickly emerging roadblock in patient care is, unfortunately, access to medications due to rising cost and poor insurance coverage.”

The study, published in the Journal of Drugs in Dermatology, found that, when combined, the nanoparticles and the medication are more effective than both alone, opening the door to potentially better and more tolerable treatment regimens. An additional benefit is the ability of nanoparticles to access infections in difficult to reach locations, as penetration and retaining activity across the nail plate is a common impediment for many antifungals.

“What we found was that we could impart the same antifungal activity at the highest concentrations tested of either alone by combining them at a fraction of these concentrations,” Friedman explained. “The impact of this combo, which we visualized using electron microscopy as compared to either product alone, highlighted their synergistic damaging effects at concentrations that would be completely safe to human cells.”

Given these results, the authors note that it is worth further researching the synergy of nitric oxide-releasing nanoparticles and efinaconazole against onychomycosis to determine the efficacy of the treatment in a clinical setting.

Here’s a link to and a citation for the paper,

Nitric Oxide Releasing Nanoparticles as a Strategy to Improve Current Onychomycosis Treatments by Caroline B. Costa-Orlandi, Breanne Mordorski, Ludmila M. Baltazar, Maria José S. Mendes-Giannini, Joel M. Friedman, Joshua D. Nosanchuk, Adam J. Friedman. Journal of Drugs in Dermatology, 2018; 17 (7): 717-720 July 2018 Copyright © 2018  http://jddonline.com/articles/dermatology/S1545961618P0717X/1

This paper is behind a paywall.

Wonders of curcumin: wound healing; wonders of aromatic-turmerone: stem cells

Both curcumin and turmerone are constituents of turmeric which has been long lauded for its healing properties. Michael Berger has written a Nanowerk Spotlight article featuring curcumin and some recent work on burn wound healing. Meanwhile, a ScienceDaily news item details information about a team of researchers focused on tumerone as a means for regenerating brain stem cells.

Curcumin and burn wounds

In a Sept. 22, 2014 Nanowerk Spotlight article Michael Berger sums up the curcumin research effort (referencing some of this previous articles on the topic) in light of a new research paper about burn wound healing (Note: Links have been removed),

Despite significant progress in medical treatments of severe burn wounds, infection and subsequent sepsis persist as frequent causes of morbidity and mortality for burn victims. This is due not only to the extensive compromise of the protective barrier against microbial invasion, but also as a result of growing pathogen resistance to therapeutic options.

… Dr Adam Friedman, Assistant Professor of Dermatology and Director of Dermatologic research at the Montefiore-Albert Einstein College of Medicine, tells Nanowerk. “For me, this gap fuels innovation, serving as the inspiration for my research with broad-spectrum, multi-mechanistic antimicrobial nanomaterials.”

In new work, Friedman and a team of researchers from Albert Einstein College of Medicine and Oregon State University have explored the use of curcumin nanoparticles for the treatment of infected burn wounds, an application that resulted in reduced bacterial load and enhancing wound healing.

It certainly seems promising as per the article abstract,

Curcumin-encapsulated nanoparticles as innovative antimicrobial and wound healing agent by Aimee E. Krausz, Brandon L. Adler, Vitor Cabral, Mahantesh Navati, Jessica Doerner, Rabab Charafeddine, Dinesh Chandra, Hongying Liang, Leslie Gunther, Alicea Clendaniel, Stacey Harper, Joel M. Friedman, Joshua D. Nosanchuk, & Adam J. Friedman. Nanomedicine: Nanotechnology, Biology and Medicine (article in press) published online 19 September 2014.http://www.nanomedjournal.com/article/S1549-9634%2814%2900527-9/abstract Uncorrected Proof

Burn wounds are often complicated by bacterial infection, contributing to morbidity and mortality. Agents commonly used to treat burn wound infection are limited by toxicity, incomplete microbial coverage, inadequate penetration, and rising resistance. Curcumin is a naturally derived substance with innate antimicrobial and wound healing properties. Acting by multiple mechanisms, curcumin is less likely than current antibiotics to select for resistant bacteria.

Curcumin’s poor aqueous solubility and rapid degradation profile hinder usage; nanoparticle encapsulation overcomes this pitfall and enables extended topical delivery of curcumin.

In this study, we synthesized and characterized curcumin nanoparticles (curc-np), which inhibited in vitro growth of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa in dose-dependent fashion, and inhibited MRSA growth and enhanced wound healing in an in vivo murine wound model. Curc-np may represent a novel topical antimicrobial and wound healing adjuvant for infected burn wounds and other cutaneous injuries.

Two things: This paper is behind a paywall and note the use of the term ‘in vivo’ which means they have tested on animals such as rats and mice for example, but not humans. Nonetheless, it seems a promising avenue for further exploration.

Interestingly, there was an attempt in 1995 to patent turmeric for use in wound healing as per my Dec. 26, 2011 posting which featured then current research on turmeric,

There has already been one court case regarding a curcumin patent,

Recently, turmeric came into the global limelight when the controversial patent “Use of Turmeric in Wound Healing” was awarded, in 1995, to the University of Mississippi Medical Center, USA. Indian Council of Scientific and Industrial Research (CSIR) aggressively contested this award of the patent. It was argued by them that turmeric has been an integral part of the traditional Indian medicinal system over several centuries, and therefore, is deemed to be ‘prior art’, hence is in the public domain. Subsequently, after protracted technical/legal battle USPTO decreed that turmeric is an Indian discovery and revoked the patent.

One last bit about curcumin, my April 22, 2014 posting featured work in Iran using curcumin for cancer-healing.

Tumerone

This excerpt from a Sept. 25, 2014, news item in ScienceDaily represents the first time that tumerone has been mentioned here,

A bioactive compound found in turmeric promotes stem cell proliferation and differentiation in the brain, reveals new research published today in the open access journal Stem Cell Research & Therapy. The findings suggest aromatic turmerone could be a future drug candidate for treating neurological disorders, such as stroke and Alzheimer’s disease.

A Sept. 25, 2014 news release on EurekAlert provides more information,

The study looked at the effects of aromatic (ar-) turmerone on endogenous neutral stem cells (NSC), which are stem cells found within adult brains. NSC differentiate into neurons, and play an important role in self-repair and recovery of brain function in neurodegenerative diseases. Previous studies of ar-turmerone have shown that the compound can block activation of microglia cells. When activated, these cells cause neuroinflammation, which is associated with different neurological disorders. However, ar-turmerone’s impact on the brain’s capacity to self-repair was unknown.

Researchers from the Institute of Neuroscience and Medicine in Jülich, Germany, studied the effects of ar-turmerone on NSC proliferation and differentiation both in vitro and in vivo. Rat fetal NSC were cultured and grown in six different concentrations of ar-turmerone over a 72 hour period. At certain concentrations, ar-turmerone was shown to increase NSC proliferation by up to 80%, without having any impact on cell death. The cell differentiation process also accelerated in ar-turmerone-treated cells compared to untreated control cells.

To test the effects of ar-turmerone on NSC in vivo, the researchers injected adult rats with ar-turmerone. Using PET imaging and a tracer to detect proliferating cells, they found that the subventricular zone (SVZ) was wider, and the hippocampus expanded, in the brains of rats injected with ar-turmerone than in control animals. The SVZ and hippocampus are the two sites in adult mammalian brains where neurogenesis, the growth of neurons, is known to occur.

Lead author of the study, Adele Rueger, said: “While several substances have been described to promote stem cell proliferation in the brain, fewer drugs additionally promote the differentiation of stem cells into neurons, which constitutes a major goal in regenerative medicine. Our findings on aromatic turmerone take us one step closer to achieving this goal.”

Ar-turmerone is the lesser-studied of two major bioactive compounds found in turmeric. The other compound is curcumin, which is well known for its anti-inflammatory and neuroprotective properties

Here’s a link to and a citation for the paper,

Aromatic-turmerone induces neural stem cell proliferation in vitro and in vivo by Joerg Hucklenbroich, Rebecca Klein, Bernd Neumaier, Rudolf Graf, Gereon Rudolf Fink, Michael Schroeter, and Maria Adele Rueger. Stem Cell Research & Therapy 2014, 5:100  doi:10.1186/scrt500

This is an open access paper.