Tag Archives: University of North Carolina

Melting body fat with a microneedle patch

For many people this may seem like a dream come true but there is a proviso. So far researchers have gotten to the in vivo testing (mice)  with no word about human clinical trials, which means it could be quite a while, assuming human clinical trials go well, before any product comes to market. With that in mind, here’s more from a Sept.15, 2017 news item on Nanowerk,

Researchers have devised a medicated skin patch that can turn energy-storing white fat into energy-burning brown fat locally while raising the body’s overall metabolism. The patch could be used to burn off pockets of unwanted fat such as “love handles” and treat metabolic disorders like obesity and diabetes, according to researchers at Columbia University Medical Center (CUMC) and the University of North Carolina.

A Sept. 15, 2017 Columbia University Medical Center news release on EurekAlert, which originated the news item, describes the research further,

Humans have two types of fat. White fat stores excess energy in large triglyceride droplets. Brown fat has smaller droplets and a high number of mitochondria that burn fat to produce heat. Newborns have a relative abundance of brown fat, which protects against exposure to cold temperatures. But by adulthood, most brown fat is lost.

For years, researchers have been searching for therapies that can transform an adult’s white fat into brown fat–a process named browning–which can happen naturally when the body is exposed to cold temperatures–as a treatment for obesity and diabetes.

“There are several clinically available drugs that promote browning, but all must be given as pills or injections,” said study co-leader Li Qiang, PhD, assistant professor of pathology and cell biology at CUMC. “This exposes the whole body to the drugs, which can lead to side effects such as stomach upset, weight gain, and bone fractures. Our skin patch appears to alleviate these complications by delivering most drugs directly to fat tissue.”

To apply the treatment, the drugs are first encased in nanoparticles, each roughly 250 nanometers (nm) in diameter–too small to be seen by the naked eye. (In comparison, a human hair is about 100,000 nm wide.) The nanoparticles are then loaded into a centimeter-square skin patch containing dozens of microscopic needles. When applied to skin, the needles painlessly pierce the skin and gradually release the drug from nanoparticles into underlying tissue.

“The nanoparticles were designed to effectively hold the drug and then gradually collapse, releasing it into nearby tissue in a sustained way instead of spreading the drug throughout the body quickly,” said patch designer and study co-leader Zhen Gu, PhD, associate professor of joint biomedical engineering at the University of North Carolina at Chapel Hill and North Carolina State University.

The new treatment approach was tested in obese mice by loading the nanoparticles with one of two compounds known to promote browning: rosiglitazone (Avandia) or beta-adrenergic receptor agonist (CL 316243) that works well in mice but not in humans. Each mouse was given two patches–one loaded with drug-containing nanoparticles and another without drug–that were placed on either side of the lower abdomen. New patches were applied every three days for a total of four weeks. Control mice were also given two empty patches.

Mice treated with either of the two drugs had a 20 percent reduction in fat on the treated side compared to the untreated side. They also had significantly lower fasting blood glucose levels than untreated mice.

Tests in normal, lean mice revealed that treatment with either of the two drugs increased the animals’ oxygen consumption (a measure of overall metabolic activity) by about 20 percent compared to untreated controls.

Genetic analyses revealed that the treated side contained more genes associated with brown fat than on the untreated side, suggesting that the observed metabolic changes and fat reduction were due to an increase in browning in the treated mice.

“Many people will no doubt be excited to learn that we may be able to offer a noninvasive alternative to liposuction for reducing love handles,” says Dr. Qiang. “What’s much more important is that our patch may provide a safe and effective means of treating obesity and related metabolic disorders such as diabetes.” [emphasis mine]

The patch has not been tested in humans. The researchers are currently studying which drugs, or combination of drugs, work best to promote localized browning and increase overall metabolism.

The study was supported by grants from the North Carolina Translational and Clinical Sciences Institute and the National Institutes of Health (1UL1TR001111, R00DK97455, and P30DK063608).

Notice the emphasis on health and that the funding does not seem to be from industry (the National Institutes of Health is definitely a federal US agency but I’m not familiar with the North Carolina Translational and Clinical Sciences Institute).

Getting back to the research, here’s an animation featuring the work,

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

Locally Induced Adipose Tissue Browning by Microneedle Patch for Obesity Treatment by Yuqi Zhang†, Qiongming Liu, Jicheng Yu†, Shuangjiang Yu, Jinqiang Wang, Li Qiang, and Zhen Gu. ACS Nano, Article ASAP DOI: 10.1021/acsnano.7b04348 Publication Date (Web): September 15, 2017

Copyright © 2017 American Chemical Society

This paper is behind a paywall.

I would imagine that Qiang and his colleagues will find a number of business entities will be lining up to fund their work. While the researchers may be focused primarily on health issues, I imagine business types will be seeing dollar signs (very big ones with many zeroes).

Nanozymes as an antidote for pesticides

Should you have concerns about exposure to pesticides or chemical warfare agents (timely given events in Syria as per this April 4, 2017 news item on CBC [Canadian Broadcasting News Corporation] online) , scientists at the Lomonosov Moscow State University have developed a possible antidote according to a March 8,, 2017 news item on phys.org,

Members of the Faculty of Chemistry of the Lomonosov Moscow State University have developed novel nanosized agents that could be used as efficient protective and antidote modalities against the impact of neurotoxic organophosphorus compounds such as pesticides and chemical warfare agents. …

A March 7, 2017 Lomonosov Moscow State University press release on EurekAlert, which originated the news item, describes the work in detail,

A group of scientists from the Faculty of Chemistry under the leadership of Prof. Alexander Kabanov has focused their research supported by a “megagrant” on the nanoparticle-based delivery to an organism of enzymes, capable of destroying toxic organophosphorous compounds. Development of first nanosized drugs has started more than 30 years ago and already in the 90-s first nanomedicines for cancer treatment entered the market. First such medicines were based on liposomes – spherical vesicles made of lipid bilayers. The new technology, developed by Kabanov and his colleagues, uses an enzyme, synthesized at the Lomonosov Moscow State University, encapsulated into a biodegradable polymer coat, based on an amino acid (glutamic acid).

Alexander Kabanov, Doctor of Chemistry, Professor at the Eshelman School of Pharmacy of the University of North Carolina (USA) and the Faculty of Chemistry, M. V. Lomonosov Moscow State University, one of the authors of the article explains: “At the end of the 80-s my team (at that time in Moscow) and independently Japanese colleagues led by Prof. Kazunori Kataoka from Tokyo began using polymer micelles for small molecules delivery. Soon the nanomedicine field has “exploded”. Currently hundreds of laboratories across the globe work in this area, applying a wide variety of approaches to creation of such nanosized agents. A medicine on the basis of polymeric micelles, developed by a Korean company Samyang Biopharm, was approved for human use in 2006.”

Professor Kabanov’s team after moving to the USA in 1994 focused on development of polymer micelles, which could include biopolymers due to electrostatic interactions. Initially chemists were interested in usage of micelles for RNA and DNA delivery but later on scientists started actively utilizing this approach for delivery of proteins and, namely, enzymes, to the brain and other organs.

Alexander Kabanov says: “At the time I worked at the University of Nebraska Medical Center, in Omaha (USA) and by 2010 we had a lot of results in this area. That’s why when my colleague from the Chemical Enzymology Department of the Lomonosov Moscow State University, Prof. Natalia Klyachko offered me to apply for a megagrant the research theme of the new laboratory was quite obvious. Specifically, to use our delivery approach, which we’ve called a “nanozyme”, for “improvement” of enzymes, developed by colleagues at the Lomonosov Moscow State University for its further medical application.”

Scientists together with the group of enzymologists from the Lomonosov Moscow State University under the leadership of Elena Efremenko, Doctor of Biological Sciences, have chosen organophosphorus hydrolase as a one of the delivered enzymes. Organophosphorus hydrolase is capable of degrading toxic pesticides and chemical warfare agents with very high rate. However, it has disadvantages: because of its bacterial origin, an immune response is observed as a result of its delivery to an organism of mammals. Moreover, organophosphorus hydrolase is quickly removed from the body. Chemists have solved this problem with the help of a “self-assembly” approach: as a result of inclusion of organophosphorus hydrolase enzyme in a nanozyme particles the immune response becomes weaker and, on the contrary, both the storage stability of the enzyme and its lifetime after delivery to an organism considerably increase. Rat experiments have proved that such nanozyme efficiently protects organisms against lethal doses of highly toxic pesticides and even chemical warfare agents, such as VX nerve gas.

Alexander Kabanov summarizes: “The simplicity of our approach is very important. You could get an organophosphorus hydrolase nanozyme by simple mixing of aqueous solutions of anenzyme and safe biocompatible polymer. This nanozyme is self-assembled due to electrostatic interaction between a protein (enzyme) and polymer”.

According to the scientist’s words the simplicity and technological effectiveness of the approach along with the obtained promising results of animal experiments bring hope that this modality could be successful and in clinical use.

Members of the Faculty of Chemistry of the Lomonosov Moscow State University, along with scientists from the 27th Central Research Institute of the Ministry of Defense of the Russian Federation, the Eshelman School of Pharmacy of the University of North Carolina at Chapel Hill (USA) and the University of Nebraska Medical Center (UNC) have taken part in the Project.

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

A simple and highly effective catalytic nanozyme scavenger for organophosphorus neurotoxins by Elena N. Efremenko, Ilya V. Lyagin, Natalia L. Klyachko, Tatiana Bronich, Natalia V. Zavyalova, Yuhang Jiang, Alexander V. Kabanov. Journal of Controlled Release Volume 247, 10 February 2017, Pages 175–181  http://dx.doi.org/10.1016/j.jconrel.2016.12.037

This paper is behind a paywall.

Nanotechnology-enabled dengue virus vaccine

Here’s news of work-in-progress for a dengue virus vaccine and, possibly, a Zika virus vaccine too. From a Nov. ??, 2016 University of North Carolina news release,

Scientists at the UNC School of Medicine are working to develop a nanoparticle vaccine to protect against the four serotypes of dengue virus, which infects more than 350 million people across the globe each year.

Aravinda de Silva, PhD, professor of microbiology and immunology, and a post-doctoral researcher Stefan Metz, PhD, recently published the latest on their vaccine development efforts in PLOS Neglected Tropical Diseases.

The nanoparticle platform was produced with PRINT (Particle Replication in Non-wetting Templates) technology. Joseph DeSimone, PhD, the Chancellor’s Eminent Professor of Chemistry and a joint professor in the Department of Pharmacology at UNC, developed PRINT, a nano-molding technique, in 2004.

Rather than using a killed or attenuated virus to develop a vaccine for dengue, de Silva’s lab is focusing on “expressing the E protein and attaching it to nanoparticles to induce good immune responses,” Metz said.

The nanoparticle vaccine platform can be safer to certain populations than vaccines that use either live or killed virus, he said.

One of the many complexities about developing a successful dengue vaccine, Metz explained, is that there are four serotypes of the virus, which means researchers need to develop a vaccine that provides immunity against all four serotypes.

“There are currently several vaccines in trial and development for dengue,” Metz said. “One vaccine has gone through all three clinical trial phases and has been licensed in some countries. Although these vaccines produce good antibody responses, a large part of the population still wasn’t protected from each of the serotypes.

“With dengue, you need to vaccinate people against all four serotypes at once in order to protect people. That’s why we’re combing the different serotypes.”

In their most recent study, de Silva and Metz focused their efforts on the second serotype. Now, they’re moving forward with the same studies for serotypes one, three and four.

“In the study, we express the E protein, which is found on the surface of the virus particle,” Metz explained. “This protein is organized in a very complex way, and this complex organization exposes isotopes that are important to induce protective immune response.”

De Silva and Metz were recently named to a global research consortium to tackle Zika, and they’re using the same nanoparticle vaccine platform as they work to develop a Zika vaccine.

“Globally, if you look at the numbers, dengue is still a much bigger problem than Zika,” Metz said, noting that an estimated 25,000 people die from dengue infections each year. “If you get dengue, you might not even notice it. If you do get clinical symptoms during a first infection of dengue, you might feel like you have a feverish flu. A lot of people don’t even know it because if you’re not feeling well for a couple days, you don’t necessarily think that it’s caused by a dengue virus infection.

“However, if you were infected by the first serotype and you had a secondary infection with a different serotype, that’s when the more severe diseases can come up – stress syndromes, hemorrhagic diseases – those can be fatal diseases,” Metz said. “There are thousands and thousands of people dying from those diseases each year.”

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

Precisely Molded Nanoparticle Displaying DENV-E Proteins Induces Robust Serotype-Specific Neutralizing Antibody Responses by Stefan W. Metz, Shaomin Tian, Gabriel Hoekstra, Xianwen Yi, Michelle Stone, Katie Horvath, Michael J. Miley, Joseph DeSimone, Chris J. Luft, Aravinda M. de Silva. PLOS http://dx.doi.org/10.1371/journal.pntd.0005071  Published: October 20, 2016

This paper is open access.

Videos about how nano will change the world; NISE Net Annual Meeting; catch up mode (innovation in Canada)

The American Chemical Society held a 2nd NanoTube Video contest (mentioned in my July 22, 2009 posting) about how nanotechnology will change the world and has announced the winners. The top prize of $500 was awarded to Natalie Herring, et al (University of North Carolina) for NanoGirls about solar nanotechnology. You can see the top winning video and get more details on Nanowerk News here.

I don’t know how I missed it but NISE Net (Nanoscale Informal Science Education Network) is having its 2009 annual meeting in San Francisco, Sept. 14 – 16, 2009. I caught the notice on Andrew Maynard’s website, 2020 Science, where he gives a preview of what he will be discussing at the meeting, ‘The low down on nanotechnology safety, 10 helpful resources‘.

I also checked out his entry on Helter skelter nanotechnology which is a comment on a news release (from the Project on Emerging Nanotechnologies where Andrew works) which appears to have been translated and retranslated with some interesting results as the original makes its way back to English. It reminded me of my favourite (to date) CBC (Canadian Broadcasting Corporation) online news item.  It’s a 2008 announcement for a new nanotechnology-type centre in Alberta and the writer decided to provide an explanation of nanotechnolgy. From the news item,

Nanotechnology, which is Latin for “dwarf technology,” [emphasis mine] has medical and industrial applications. It is the science of building machines on an atomic and molecular scale, or the making or manipulating of tiny particles such as atoms and molecules on the scale of a nanometre, which is one-billionth of a metre.

Yes, nano is from classical/ancient Greek (I blush to admit I missed that in my delight with ‘dwarf technology’). If you want to see the phrase in its native habitat, go here. It’s in one of the final paragraphs.

As for innovation in Canada, I’ve been catching up on Rob Annan’s Don’t leave Canada behind postings. His latest, Why funding for basic research is essential, provides some interesting statistics (which he sources) on Canadian academic research. In short, we do well by our academic research; it’s the industry research which is a problem (Canadian business does not do much of its own research and, these days, is doing less, see the statistics Rob presents) so tying academic research to industry does not solve the problem.

It’s not just the size, it’s the shape of your nanoparticles

There’s an interesting piece on nanomedicine in Scientific American about some research that was conducted by chemistry professor Joseph DeSimone at the University of North Carolina (at Chapel Hill) about the most effective nanotransport for drug therapy. They concluded that the shape of nanoparticle used as the delivery system was an important factor in its effectiveness. There’s more here in an article by Larry Greenemeier.

Richard Jones, in his blog Soft Machines, offers his thoughts about the latest UK public dialogue programme about nanotechnology. This one focused on nanomedicine.  He first provides some information about a recent call for nanomedicine proposals, so keep reading if public dialogue is your interest. The full report for the public dialogue project that Jones mentions is here but if you’re short for time, read Jones’ posting.

Now back to my dissertation project, The Nanotech Mysteries.