Tag Archives: Amy S. Paller

Can nanoparticles pass through the skin or not?

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Researchers at the University of Bath (England) have proved that nanoparticles do not penetrate the skin, according to the Oct. 1, 2012 news item on Nanowerk,

 Research by scientists at the University of Bath is challenging claims that nanoparticles in medicated and cosmetic creams are able to transport and deliver active ingredients deep inside the skin.
Nanoparticles, which are tiny particles that are less than one hundredth of the thickness of a human hair, are used in sunscreens and some cosmetic and pharmaceutical creams.
The Bath study (“Objective assessment of nanoparticle disposition in mammalian skin after topical exposure”) discovered that even the tiniest of nanoparticles did not penetrate the skin’s surface.
These findings have implications for pharmaceutical researchers and cosmetic companies that design skin creams with nanoparticles that are supposed to transport ingredients to the deeper layers of the skin. [emphasis mine]

Back in July 2012, a research team at Northwestern University claimed to have successfully delivered gene regulation technology using moisturizers to penetrate the skin barrier, excerpted from my July 4, 2012 posting,

The news item originated from a July 2, 2012 news release, by Marla Paul for Northwestern University, which provides more details about the researchers,

“The technology developed by my collaborator Chad Mirkin and his lab is incredibly exciting because it can break through the skin barrier,” said co-senior author Amy S. Paller, M.D., the Walter J. Hamlin Professor, chair of dermatology and professor of pediatrics at Northwestern University Feinberg School of Medicine. She also is director of Northwestern’s Skin Disease Research Center.

…

A co-senior author of the paper, Mirkin is the George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences and professor of medicine, chemical and biological engineering, biomedical engineering and materials science and engineering. He also is the director of Northwestern’s International Institute for Nanotechnology.

…

Interdisciplinary research is a hallmark of Northwestern. Paller and Mirkin said their work highlights the power of physician-scientists and scientists and engineers from other fields coming together to address a difficult medical problem.

“This all happened because of our world-class presence in both cancer nanotechnology and skin disease research,” Paller said. “In putting together the Skin Disease Research Center proposal, I reached out to Chad to see if his nanostructures might be applied to skin disease. We initially worked together through a pilot project of the center, and now the rest is history.”

There’s more about how the nanoscale structures make their way through the skin but it seems the team from the University of Bath are prepared to contradict this claim, from the University of Bath’s Oct. 1,2012 news release (which originated the news item on Nanowerk),

Research by scientists at the University of Bath is challenging claims that nanoparticles in medicated and cosmetic creams are able to transport and deliver active ingredients deep inside the skin.

…

The Bath study discovered that even the tiniest of nanoparticles did not penetrate the skin’s surface.

These findings have implications for pharmaceutical researchers and cosmetic companies that design skin creams with nanoparticles that are supposed to transport ingredients to the deeper layers of the skin.

However the findings will also allay safety concerns that potentially harmful nanoparticles such as those used in sunscreens can be absorbed into the body.

The scientists used a technique called laser scanning confocal microscopy to examine whether fluorescently-tagged polystyrene beads, ranging in size from 20 to 200 nanometers, were absorbed into the skin. [emphasis mine]

They found that even when the skin sample had been partially compromised by stripping the outer layers with adhesive tape, the nanoparticles did not penetrate the skin’s outer layer, known as the stratum corneum.

I note they tested nanostructures larger than 20 nanometers so it’s possible that nanostructures that measure less than 20 nanometers could penetrate skin, non? However, it seems the structure used to ‘penetrate’ the skin by the team Northwestern University are considerably larger (excerpted from my July 4, 2012 posting),

The topical delivery of gene regulation technology to cells deep in the skin is extremely difficult because of the formidable defenses skin provides for the body. The Northwestern approach takes advantage of drugs consisting of novel spherical arrangements of nucleic acids. These structures, each about 1,000 times smaller than the diameter of a human hair, have the unique ability to recruit and bind to natural proteins that allow them to traverse the skin and enter cells.

(Side note: I believe a structure 1,000 times smaller than the diameter of a human hair would be measured in microns not nanometers.) I gather it’s the use of the nucleic acids in specialized formulations by the Northwestern team which make nanoparticle entry past the skin possible which contrasts with the work done by the University of Bath researchers who tested nanoparticles in standard cosmetic formulations.

Penetrating the skin barrier

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Researchers at Northwestern University (Illinois, US) have found a way to deliver gene regulation technology using skin moisturizers. From the July 3, 2012 news item on Science Blog,

A team led by a physician-scientist and a chemist — from the fields of dermatology and nanotechnology — is the first to demonstrate the use of commercial moisturizers to deliver gene regulation technology that has great potential for life-saving therapies for skin cancers.

The topical delivery of gene regulation technology to cells deep in the skin is extremely difficult because of the formidable defenses skin provides for the body. The Northwestern approach takes advantage of drugs consisting of novel spherical arrangements of nucleic acids. These structures, each about 1,000 times smaller than the diameter of a human hair, have the unique ability to recruit and bind to natural proteins that allow them to traverse the skin and enter cells.

Applied directly to the skin, the drug penetrates all of the skin’s layers and can selectively target disease-causing genes while sparing normal genes. Once in cells, the drug simply flips the switch of the troublesome genes to “off.”

The news item originated from a July 2, 2012 news release, by Marla Paul for Northwestern University, which provides more details about the researchers,

“The technology developed by my collaborator Chad Mirkin and his lab is incredibly exciting because it can break through the skin barrier,” said co-senior author Amy S. Paller, M.D., the Walter J. Hamlin Professor, chair of dermatology and professor of pediatrics at Northwestern University Feinberg School of Medicine. She also is director of Northwestern’s Skin Disease Research Center.

…

A co-senior author of the paper, Mirkin is the George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences and professor of medicine, chemical and biological engineering, biomedical engineering and materials science and engineering. He also is the director of Northwestern’s International Institute for Nanotechnology.

…

Interdisciplinary research is a hallmark of Northwestern. Paller and Mirkin said their work highlights the power of physician-scientists and scientists and engineers from other fields coming together to address a difficult medical problem.

“This all happened because of our world-class presence in both cancer nanotechnology and skin disease research,” Paller said. “In putting together the Skin Disease Research Center proposal, I reached out to Chad to see if his nanostructures might be applied to skin disease. We initially worked together through a pilot project of the center, and now the rest is history.”

As for the work itself, here are more details from Paul’s news release,

The key is the nanostructure’s spherical shape and nucleic acid density. Normal (linear) nucleic acids cannot get into cells, but these spherical nucleic acids can. Small interfering RNA (siRNA) surrounds a gold nanoparticle like a shell; the nucleic acids are highly oriented, densely packed and form a tiny sphere. The RNA’s sequence is programmed to target the disease-causing gene.

“We now can go after a whole new set of diseases,” Mirkin said. “Thanks to the Human Genome Project and all of the genomics research over the last two decades, we have an enormous number of known targets. And we can use the same tool for each, the spherical nucleic acid. We simply change the sequence to match the target gene. That’s the power of gene regulation technology.”

The nanostructures were developed in Mirkin’s lab on the Evanston campus and then combined with a commercial moisturizer. Next, down in Paller’s Chicago lab, the researchers applied the therapeutic ointment to the skin of mice and to human epidermis. The nanostructures were designed to target epidermal growth factor receptor (EGFR), a biomarker associated with a number of cancers.

In both cases, the drug broke through the epidermal layer and penetrated the skin very deeply, with cells taking up 100 percent of the nanostructures. They selectively knocked down the EGFR gene, decreasing the production of the problem proteins.

After a month of continued application of the ointment, there was no evidence of side effects, inappropriate triggering of the immune system or accumulation of the particles in organs. The treatment is skin specific and doesn’t interfere with other cells.

After all the concerns  about nanosunscreens and nanoparticles penetrating the skin raised by civil society groups, the Friends of the Earth in particular, it’s interesting to note that doctors and scientists consider penetration of the skin barrier to be extremely difficult. Of course, they seem to have solved that problem which means the chorus of concerns may rise to new heights.