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MIT professor Paula Hammond (right) and Bryan Hsu PhD’ 14 have developed a nanoscale film that can be used to deliver medication, either directly through injections, or by coating implantable medical devices. Photo: Dominick Reuter

Nanoscale, biodegradable drug-delivery method could provide a year or more of steady doses.

About one in four older adults suffers from chronic pain. Many of those people take medication, usually as pills. But this is not an ideal way of treating pain: Patients must take medicine frequently, and can suffer side effects, since the contents of pills spread through the bloodstream to the whole body.

Now researchers at MIT have refined a technique that could enable pain medication and other drugs to be released directly to specific parts of the body — and in steady doses over a period of up to 14 months.  The method uses biodegradable, nanoscale “thin films” laden with drug molecules that are absorbed into the body in an incremental process.

“It’s been hard to develop something that releases [medication] for more than a couple of months,” says Paula Hammond, the David H. Koch Professor in Engineering at MIT, and a co-author of a new paper on the advance. “Now we’re looking at a way of creating an extremely thin film or coating that’s very dense with a drug, and yet releases at a constant rate for very long time periods.”

In the paper, published today in the Proceedings of the National Academy of Sciences, the researchers describe the method used in the new drug-delivery system, which significantly exceeds the release duration achieved by most commercial controlled-release biodegradable films.

“You can potentially implant it and release the drug for more than a year without having to go in and do anything about it,” says Bryan Hsu PhD ’14, who helped develop the project as a doctoral student in Hammond’s lab. “You don’t have to go recover it. Normally to get long-term drug release, you need a reservoir or device, something that can hold back the drug. And it’s typically nondegradable. It will release slowly, but it will either sit there and you have this foreign object retained in the body, or you have to go recover it.”

Layer by layer

The paper was co-authored by Hsu, Myoung-Hwan Park of Shamyook University in South Korea, Samantha Hagerman ’14, and Hammond, whose lab is in the Koch Institute for Integrative Cancer Research at MIT.

The research project tackles a difficult problem in localized drug delivery: Any biodegradable mechanism intended to release a drug over a long time period must be sturdy enough to limit hydrolysis, a process by which the body’s water breaks down the bonds in a drug molecule. If too much hydrolysis occurs too quickly, the drug will not remain intact for long periods in the body. Yet the drug-release mechanism needs to be designed such that a drug molecule does, in fact, decompose in steady increments.

To address this, the researchers developed what they call a “layer-by-layer” technique, in which drug molecules are effectively attached to layers of thin-film coating. In this specific case, the researchers used diclofenac, a nonsteroidal anti-inflammatory drug that is often prescribed for osteoarthritis and other pain or inflammatory conditions. They then bound it to thin layers of poly-L-glutamatic acid, which consists of an amino acid the body reabsorbs, and two other organic compounds. The film can be applied onto degradable nanoparticles for injection into local sites or used to coat permanent devices, such as orthopedic implants.

In tests, the research team found that the diclofenac was steadily released over 14 months. Because the effectiveness of pain medication is subjective, they evaluated the efficacy of the method by seeing how well the diclofenac blocked the activity of cyclooxygenase (COX), an enzyme central to inflammation in the body.

“We found that it remains active after being released,” Hsu says, meaning that the new method does not damage the efficacy of the drug. Or, as the paper notes, the layer-by-layer method produced “substantial COX inhibition at a similar level” to pills.

The method also allows the researchers to adjust the quantity of the drug being delivered, essentially by adding more layers of the ultrathin coating.

A viable strategy for many drugs

Hammond and Hsu note that the technique could be used for other kinds of medication; an illness such as tuberculosis, for instance, requires at least six months of drug therapy.

“It’s not only viable for diclofenac,” Hsu says. “This strategy can be applied to a number of drugs.”

Indeed, other researchers who have looked at the paper say the potential medical versatility of the thin-film technique is of considerable interest.

“I find it really intriguing because it’s broadly applicable to a lot of systems,” says Kathryn Uhrich, a professor in the Department of Chemistry and Chemical Biology at Rutgers University, adding that the research is “really a nice piece of work.”

To be sure, in each case, researchers will have to figure out how best to bind the drug molecule in question to a biodegradable thin-film coating. The next steps for the researchers include studies to optimize these properties in different bodily environments and more tests, perhaps with medications for both chronic pain and inflammation.

A major motivation for the work, Hammond notes, is “the whole idea that we might be able to design something using these kinds of approaches that could create an [easier] lifestyle” for people with chronic pain and inflammation.

Hsu and Hammond were involved in all aspects of the project and wrote the paper, while Hagerman and Park helped perform the research, and Park helped analyze the data.

The research described in the paper was supported by funding from the U.S. Army and the U.S. Air Force.

It’s time for an update on graphene, that super material of the future! Scientists have come up with some new ways of making it that are easier and cheaper than ever before.

“Fascination with this material stems from its remarkable physical properties and the potential applications these properties offer for the future. Although scientists knew one atom thick, two-dimensional crystal graphene existed, no-one had worked out how to extract it from graphite.”

 

 

More ….

Charge Your Cell Phone In 5 Seconds

Supercapacitors: They’ll enable you to charge your cell phone in 5 seconds, or an electric car in about a minute. They’re cheap, biodegradable, never wear out and as Trace’ll tell you, could be powering your life sooner than you’d think.

 

 

Still More …

Scientists cook up material 200 times stronger than steel out of soybean oil

Soyben Graphene 8223748-16x9-large“Many production techniques involve the use of intense heat in a vacuum, and expensive ingredients like high-purity metals and explosive compressed gases. Now a team of Australian scientists has detailed how they turned cheap everyday ingredients into graphene under normal air conditions. They said the research, published today in the journal Nature Communications, may open up a new avenue for the low-cost synthesis of the highly sought-after material.” Click on the Link below to read more:

Scientists cook up material 200 times stronger than steel out of soybean oil


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The way energy is produced, distributed and consumed around the world is undergoing fundamental change of almost unprecedented proportions. This is commonly referred to as the “energy transition”. (watch the video)

 

The Global Energy Architecture Performance Index 2017 (EAPI), tackles elements of this transition in its fifth annual edition, as do the global Regulatory Indicators for Sustainable Energy (RISE) released by the World Bank a month earlier. Of specific interest to this essay are the underlying issues of governance and regulation and their relationship to progress towards sustainable and secure energy systems. In UN development terms, this focus helps us consider the links between Sustainable Development Goal (SDG) 7, which addresses energy, and SDG 16, which is about peace and justice.

Researchers have developed a rubber-like fiber, shown here, that can flex and stretch while simultaneously delivering both optical impulses, for optoelectronic stimulation, and electrical connections, for stimulation and monitoring. Image: Chi (Alice) Lu and Seongjun Park

Rubbery, multifunctional fibers could be used to study spinal cord neurons and potentially restore function.

Implantable fibers have been an enormous boon to brain research, allowing scientists to stimulate specific targets in the brain and monitor electrical responses. But similar studies in the nerves of the spinal cord, which might ultimately lead to treatments to alleviate spinal cord injuries, have been more difficult to carry out.

That’s because the spine flexes and stretches as the body moves, and the relatively stiff, brittle fibers used today could damage the delicate spinal cord tissue.

Now, researchers have developed a rubber-like fiber that can flex and stretch while simultaneously delivering both optical impulses, for optoelectronic stimulation, and electrical connections, for stimulation and monitoring. The new fibers are described in a paper in the journal Science Advances, by MIT graduate students Chi (Alice) Lu and Seongjun Park, Professor Polina Anikeeva, and eight others at MIT, the University of Washington, and Oxford University.

“I wanted to create a multimodal interface with mechanical properties compatible with tissues, for neural stimulation and recording,” as a tool for better understanding spinal cord functions, says Lu. But it was essential for the device to be stretchable, because “the spinal cord is not only bending but also stretching during movement.” The obvious choice would be some kind of elastomer, a rubber-like compound, but most of these materials are not adaptable to the process of fiber drawing, which turns a relatively large bundle of materials into a thread that can be narrower than a hair.

The spinal cord “undergoes stretches of about 12 percent during normal movement,” says Anikeeva, who is the Class of 1942 Career Development Professor in the Department of Materials Science and Engineering. “You don’t even need to get into a ‘downward dog’ [yoga position] to have such changes.” So finding a material that can match that degree of stretchiness could potentially make a big difference to research. “The goal was to mimic the stretchiness and softness and flexibility of the spinal cord,” she says. “You can match the stretchiness with a rubber. But drawing rubber is difficult — most of them just melt,” she says.

“Eventually, we’d like to be able to use something like this to combat spinal cord injury. But first, we have to have biocompatibility and to be able to withstand the stresses in the spinal cord without causing any damage,” she says.

 

 

 

 

 

 

 

 

 

The fibers are not only stretchable but also very flexible. “They’re so floppy, you could use them to do sutures, and do light delivery at the same time,” professor Polina Anikeeva says. (Video: Chi (Alice) Lu and Seongjun Park)

The team combined a newly developed transparent elastomer, which could act as a waveguide for optical signals, and a coating formed of a mesh of silver nanowires, producing a conductive layer for the electrical signals. To process the transparent elastomer, the material was embedded in a polymer cladding that enabled it to be drawn into a fiber that proved to be highly stretchable as well as flexible, Lu says. The cladding is dissolved away after the drawing process.

After the entire fabrication process, what’s left is the transparent fiber with electrically conductive, stretchy nanowire coatings. “It’s really just a piece of rubber, but conductive,” Anikeeva says. The fiber can stretch by at least 20 to 30 percent without affecting its properties, she says.

The fibers are not only stretchable but also very flexible. “They’re so floppy, you could use them to do sutures and deliver light  at the same time,” she says.

“We’re the first to develop something that enables simultaneous electrical recording and optical stimulation in the spinal cords of freely moving mice,” Lu says. “So we hope our work opens up new avenues for neuroscience research.” Scientists doing research on spinal cord injuries or disease usually must use larger animals in their studies, because the larger nerve fibers can withstand the more rigid wires used for stimulus and recording. While mice are generally much easier to study and available in many genetically modified strains, there was previously no technology that allowed them to be used for this type of research, she says.

“There are many different types of cells in the spinal cord, and we don’t know how the different types respond to recovery, or lack of recovery, after an injury,” she says. These new fibers, the researchers hope, could help to fill in some of those blanks.

The team included Alexander Derry, Chong Hou, Siyuan Rao, Jeewoo Kang, and professor Yoel Fink at MIT; Tom Richner and professor Chet Mortiz at the University of Washington; and Imogen Brown at Oxford University. The research was supported by the National Science Foundation, the National Institute of Neurological Disorders and Stroke, the U.S. Army Research Laboratory, and the U.S. Army Research Office through the Institute for Soldier Nanotechnologies at MIT.

A graphene membrane. Credit: The University of Manchester

 

“By 2025 the UN expects that 14% of the world’s population will encounter water scarcity.”

Graphene-oxide membranes have attracted considerable attention as promising candidates for new filtration technologies. Now the much sought-after development of making membranes capable of sieving common salts has been achieved.

New research demonstrates the real-world potential of providing for millions of people who struggle to access adequate clean water sources.

The new findings from a group of scientists at The University of Manchester were published today in the journal Nature Nanotechnology. Previously graphene-oxide membranes have shown exciting potential for gas separation and water filtration.

Graphene-oxide membranes developed at the National Graphene Institute have already demonstrated the potential of filtering out small nanoparticles, organic molecules, and even large salts. Until now, however, they couldn’t be used for sieving common salts used in technologies, which require even smaller sieves.

Previous research at The University of Manchester found that if immersed in water, graphene-oxide membranes become slightly swollen and smaller salts flow through the membrane along with water, but larger ions or molecules are blocked.

The Manchester-based group have now further developed these and found a strategy to avoid the swelling of the membrane when exposed to water. The in the membrane can be precisely controlled which can sieve common salts out of salty water and make it safe to drink.

As the effects of climate change continue to reduce modern city’s water supplies, wealthy modern countries are also investing in desalination technologies. Following the severe floods in California major wealthy cities are also looking increasingly to alternative water solutions.

WEF 2017 graphene-water-071115-rtrde3r1-628x330 (2)World Economic Forum: Can Graphene Make the World’s Water Clean?

 

 

 

 

When the common salts are dissolved in water, they always form a ‘shell’ of around the salts molecules. This allows the tiny capillaries of the graphene-oxide membranes to block the from flowing along with the water. Water molecules are able to pass through the membrane barrier and flow anomalously fast which is ideal for application of these membranes for desalination.

Professor Rahul Nair, at The University of Manchester said: “Realisation of scalable membranes with uniform pore size down to atomic scale is a significant step forward and will open new possibilities for improving the efficiency of desalination .

“This is the first clear-cut experiment in this regime. We also demonstrate that there are realistic possibilities to scale up the described approach and mass produce graphene-based membranes with required sieve sizes.”

Mr. Jijo Abraham and Dr. Vasu Siddeswara Kalangi were the joint-lead authors on the research paper: “The developed membranes are not only useful for desalination, but the atomic scale tunability of the pore size also opens new opportunity to fabricate membranes with on-demand filtration capable of filtering out ions according to their sizes.” said Mr. Abraham.

By 2025 the UN expects that 14% of the world’s population will encounter water scarcity. This technology has the potential to revolutionize water filtration across the world, in particular in countries which cannot afford large scale desalination plants.

It is hoped that graphene-oxide systems can be built on smaller scales making this technology accessible to countries which do not have the financial infrastructure to fund large plants without compromising the yield of fresh produced.

Explore further: Researchers develop hybrid nuclear desalination technique with improved efficiency

More information: Tunable sieving of ions using graphene oxide membranes, Nature Nanotechnology, nature.com/articles/doi:10.1038/nnano.2017.21


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