Colorful solution to a chemical industry bottleneck – KAUST Researchers Develop an “hourglass shape” Graphene-Oxide Membrane to rapidly separate chemical mixtures – Application Pharmaceuticals (other chemical mixtures)


KAUST 2 Color 809

A graphene-oxide membrane design inspired by nature swiftly separates solvent molecules.

The nanoscale water channels that nature has evolved to rapidly shuttle water molecules into and out of cells could inspire new materials to clean up chemical and pharmaceutical production. KAUST researchers have tailored the structure of graphene-oxide layers to mimic the hourglass shape of these biological channels, creating ultrathin membranes to rapidly separate chemical mixtures.

“In making pharmaceuticals and other chemicals, separating mixtures of organic molecules is an essential and tedious task,” says Shaofei Wang, postdoctoral researcher in Suzana Nuñes lab at KAUST. One option to make these chemical separations faster and more efficient is through selectively permeable membranes, which feature tailored nanoscale channels that separate molecules by size.

But these membranes typically suffer from a compromise known as the permeance-rejection tradeoff. This means narrow channels may effectively separate the different-sized molecules, but they also have an unacceptably low flow of solvent through the membrane, and vice versa—they flow fast enough, but perform poorly at separation.

Nuñes, Wang and the team have taken inspiration from nature to overcome this limitation. Aquaporins have an hourglass-shaped channel: wide at each end and narrow at the hydrophobic middle section. This structure combines high solvent permeance with high selectivity. Improving on nature, the team has created channels that widen and narrow in a synthetic membrane.

The membrane is made from flakes of a two-dimensional carbon nanomaterial called graphene oxide. The flakes are combined into sheets several layers thick with graphene oxide. Organic solvent molecules are small enough to pass through the narrow channels between the flakes to cross the membrane, but organic molecules dissolved in the solvent are too large to take the same path. The molecules can therefore be separated from the solvent.

To boost solvent flow without compromising selectivity, the team introduced spacers between the graphene-oxide layers to widen sections of the channel, mimicking the aquaporin structure. The spacers were formed by adding a silicon-based molecule into the channels that, when treated with sodium hydroxide, reacted in situ to form silicon-dioxide nanoparticles. “The hydrophilic nanoparticles locally widen the interlayer channels to enhance the solvent permeance,” Wang explains.

When the team tested the membrane’s performance with solutions of organic dyes, they found that it rejected at least 90 percent of dye molecules above a threshold size of 1.5 nanometers. Incorporating the nanoparticles enhanced solvent permeance 10-fold, without impairing selectivity. The team also found there was enhanced membrane strength and longevity when chemical cross-links formed between the graphene-oxide sheets and the nanoparticles.

“The next step will be to formulate the nanoparticle graphene-oxide material into hollow-fiber membranes suitable for industrial applications,” Nuñes says.

References

Wang, S., Mahalingam, D., Sutisna, B. & Nunes, S.P. 2D-dual-spacing channel membranes for high performance organic solvent nanofiltration. Journal of Materials Chemistry Aadvance online publication, 10 January 2019.| article

 

Advertisements

BIG Discoveries from Tiny Particles – from Photonics to Pharmaceuticals, materials made with Polymer Nanoparticles hold promise for products of the future – U of Delaware


Big discovery nanoparticles 181008101017_1_540x360
In this illustration, arrows indicate the vibrational activity of particles studied by UD researchers, while the graph shows the frequencies of this vibration.
Credit: Illustration courtesy of Hojin Kim
Summary:
Understanding the mechanical properties of nanoparticles are essential to realizing their promise in being used to create exciting new products. This new research has taken a significant step toward gaining the knowledge that can lead to better performance with products using polymer nanoparticles.

From photonics to pharmaceuticals, materials made with polymer nanoparticles hold promise for products of the future. However, there are still gaps in understanding the properties of these tiny plastic-like particles.

Now, Hojin Kim, a graduate student in chemical and biomolecular engineering at the University of Delaware, together with a team of collaborating scientists at the Max Planck Institute for Polymer Research in Germany, Princeton University and the University of Trento, has uncovered new insights about polymer nanoparticles. The team’s findings, including properties such as surface mobility, glass transition temperature and elastic modulus, were published in Nature Communications.

Under the direction of MPI Prof. George Fytas, the team used Brillouin light spectroscopy, a technique that spelunks the molecular properties of microscopic nanoparticles by examining how they vibrate.

“We analyzed the vibration between each nanoparticle to understand how their mechanical properties change at different temperatures,” Kim said. “We asked, ‘What does a vibration at different temperatures indicate? What does it physically mean?’ ”

The characteristics of polymer nanoparticles differ from those of larger particles of the same material. “Their nanostructure and small size provide different mechanical properties,” Kim said. “It’s really important to understand the thermal behavior of nanoparticles in order to improve the performance of a material.”

Take polystyrene, a material commonly used in nanotechnology. Larger particles of this material are used in plastic bottles, cups and packaging materials.

“Polymer nanoparticles can be more flexible or weaker at the glass transition temperature at which they soften from a stiff texture to a soft one, and it decreases as particle size decreases,” Kim said. That’s partly because polymer mobility at small particle surface can be activated easily. It’s important to know when and why this transition occurs, since some products, such as filter membranes, need to stay strong when exposed to a variety of conditions.

For example, a disposable plastic cup made with the polymer polystyrene might hold up in boiling water — but that cup doesn’t have nanoparticles. The research team found that polystyrene nanoparticles start to experience the thermal transition at 343 Kelvin (158 degrees F), known as the softening temperature, below a glass transition temperature of 372 K (210 F) of the nanoparticles, just short of the temperature of boiling water. When heated to this point, the nanoparticles don’t vibrate — they stand completely still.

This hadn’t been seen before, and the team found evidence to suggest that this temperature may activate a highly mobile surface layer in the nanoparticle, Kim said. As particles heated up between their softening temperature and glass transition temperature, the particles interacted with each other more and more. Other research groups have previously suspected that glass transition temperature drops with decreases in particle size decreases because of differences in particle mobility, but they could not observe it directly.

“Using different method and instruments, we analyzed our data at different temperatures and actually verified there is something on the polymer nanoparticle surface that is more mobile compared to its core,” he said.

By studying interactions between the nanoparticles, the team also uncovered their elastic modulus, or stiffness.

Next up, Kim plans to use this information to build a nanoparticle film that can govern the propagation of sound waves.

Eric Furst, professor and chair of the Department of Chemical and Biomolecular Engineering at UD, is also a corresponding author on the paper.

“Hojin took the lead on this project and achieved results beyond what I could have predicted,” said Furst. “He exemplifies excellence in doctoral engineering research at Delaware, and I can’t wait to see what he does next.”

Story Source:

Materials provided by University of DelawareNote: Content may be edited for style and length.


Journal Reference:

  1. Hojin Kim, Yu Cang, Eunsoo Kang, Bartlomiej Graczykowski, Maria Secchi, Maurizio Montagna, Rodney D. Priestley, Eric M. Furst, George Fytas. Direct observation of polymer surface mobility via nanoparticle vibrationsNature Communications, 2018; 9 (1) DOI: 10.1038/s41467-018-04854-w

Nanotechnology Can Improve Safety, Effectiveness in Drug Delivery – Incorporating Nanotechnology into Drug Discovery could Increase the odds of Success


Drug Development

Formulating a drug that is not only effective, but also safe with limited side effects, is no easy task.

The likelihood of an investigational drug in a Phase 1 trial eventually receiving an FDA approval is only 9.6 percent, according to a recent analysis. At the pre-clinical level, the chances of long-term success are even lower.

Incorporating nanotechnology into drug discovery is one possible approach that could increase the odds of success for certain drug candidates, said Marina Sokolsky-Papkov, PhD, director of the Translational Nanoformulation Research Core Facility at the Center for Nanotechnology in Drug Delivery (CNDD) at the UNC Eshelman School of Pharmacy.

“It has been shown that nanotechnology is able to address a lot of the clinical development challenges that drug candidates usually face,” said Sokolsky-Papkov in an interview with R&D Magazine. “The whole idea is to take the drug, encapsulate it into a nano-carrier, which will have a different distribution profile, and prevent exposure of the drug over the whole body.”

The CNDD was established in June 2007 with the goal of enhancing the efficacy and safety of new drugs and imaging agents through the discovery and application of innovative methods of drug delivery.

To do that they established two core facilities—the Translational Nanoformulation Research Core Laboratory, which  promotes translation of new drug candidates into clinical trials through advanced formulation techniques; and the Nanomedicines Characterization Core Facility, which accelerates translation of new nanomedicines to clinic by providing their comprehensive physicochemical characterization.

“The goal is to promote collaborative research and to promote interactions between people with clinical vision and expertise and expertise in formulation techniques,” said Sokolsky-Papkov. “This will increase the chances of getting these drugs to the market.”FDA-Has-Approved-Device-to-Combat-Drug-Overdose

The benefits nano-drug delivery

Although nanomedicine isn’t brand new—the first FDA approval for a nano-based drug was in 1995—researchers are just scratching the surface of the technology’s potential.

The CNDD is investigating the use of nanotechnology to treat a wide variety of conditions, including cancer, stroke, neurodegenerative and neurodevelopmental disorders, nerve agent and pesticide poisoning and other diseases and injuries.

“We use different techniques across the board,” said Sokolsky-Papkov. “Nanotechnology can be used with existing drugs as a way to improve the current formulation or we can take a carrier formulation approach to new drugs out there.”

One approach to nanomedicine is to utilize a nanomaterial, such as liposome, as a more effective drug delivery system for an already existing therapeutic.

Nanoparticles tend to accumulate in areas that are inflamed, which is often the site of disease, explained Sokolsky-Papkov. During an inflammatory response, the blood vessel barrier often becomes “leaky.” This makes it easier for nanoparticles— equipped with a therapeutic agent to fight disease—to enter.

Nano in Drug III images

Collaboration with pharma will introduce nanotechnologies in early stage drug development

“If you encapsulate your drug in a certain size range, below 100 nanometers, it will be able to penetrate with leaky vessels and target those areas better,” said Sokolsky-Papkov.

Nanoformulations also provide an opportunity to improve efficacy of certain drugs, as they can increase the accumulation of the drug at the disease site. This is particularly useful when a drug needs to enter a hard-to-penetrate area, such as the brain.

“In our center we have research going on regarding nano-meditated delivery of therapeutic agents for the brain, both small molecule and biologics,” said Sokolsky-Papkov. “We specifically see a significantly higher accumulation of a drug and better efficacy in nanoformulation versus conventional administration systems.”

Because nanoformulations are more targeted to the site of the disease, they can also be used to reduce side effects. In conventional drug administration, the therapeutic hits all of the body’s cells and blood vessels at one high dose at the same time. However, with a nanoformulation, the drug is released in a more sustained manner, resulting in lower overall body exposure overtime. This is less toxic to the system, said Sokolsky-Papkov.

Diagnostic and imaging applications

In addition to drug delivery, nanotechnology can also be utilized in medicine for diagnostic and imaging purposes.

Several magnetic nanoparticles have been approved for clinical use in imaging. The benefits are similar to those seen in nano-drug delivery, said Sokolsky-Papkov.

“This uses the same idea that in areas associated with inflammation the accumulation of an imaging agent will be higher in an inflamed area compared to normal tissue when using nanoparticles” she explained. “Basically these nanoparticles will be labeled so that they can be tracked using standard imaging techniques.” Nano in Drug II images

During an MRI, magnetic nanoparticles interact with the magnetic field and can be tracked by observing where the image turns darker. This allows for a comparison before and after accumulation of nanoparticles to identify possible disease.

Image … impact on healthcare by delivering disease diagnosis, monitoring, implants, regenerative medicines and drug delivery, drug discovery for biomedicine.

“If you see a lot of accumulation in these areas there is something potentially going on,” said Sokolsky-Papkov.

 

Growth of industry

The field of nanomedicine is rapidly advancing, said Sokolsky-Papkov.

“The clinical models to evaluate the efficacy of nanomedicines are improving over time,” she said. “There is a lot of research and effort going to improve pre-clinical evaluations to increase collaboration between pre-clinical and clinical data, which significantly improves the chances of nano-medicines hitting the market. The number of clinical trials for different nanoformulations is increasing significantly each year.”

 

 

Advanced (SWIR) Quantum Dots Offer Solution for Tagging and Imaging the Biological Processes in LIVE Animals


nanocrystalsFluorescent quantum dots are valuable tools used to tag and image biological processes in live animals. However, precise fluorescent imaging at the cellular and molecular levels has not been possible because of non-specific fluorescence and light scattering by surrounding tissues.

Now researchers have created short wave infrared (SWIR) quantum dots that resolve many of these problems. The system was used in live mice to image working organs, take metabolic measurements, and track microvascular blood flow in normal brain and brain tumors.

“Quantum dots are small (nanoscale) particles that can be engineered to emit light at different wavelengths,” explains Behrouz Shabestari, Ph.D., director of the Optical Imaging Program at NIH’s National Institute of Biomedical Imaging and Bioengineering, which co-funded the research. “When they are injected into a live animal, the emitted fluorescent light can be seen with special cameras. By engineering the dots to bind to specific tissues of interest, researchers can use them to study biological processes in real-time.” qdot_tech_note_graph
An international group of investigators led by Moungi G. Bawendi, Ph.D., the Lester Wolfe Professor in Chemistry at the Massachusetts Institute of Technology, collaborated to create what Bawendi calls the “next-generation,” of quantum dots.
Said Bawendi, “We took advantage of the special qualities of short wave infrared light, which is essentially the ability to give a clear bright signal emitted from the tissue of interest that is not blocked or scattered by the surrounding tissues. The system allows us to view biological processes in living, moving animals with great clarity and detail.”
The work is described in the April issue of the journal Nature Biomedical Engineering (“Next-generation in vivo optical imaging with short-wave infrared quantum dots”).
experimental set-up with composite SWIR quantum dots injected into the circulation and then imaged through a cranial window in the mouse brain
The top outlines the experimental set-up with composite SWIR quantum dots injected into the circulation and then imaged through a cranial window in the mouse brain. The bottom shows the resulting fluorescent image with healthy arteries in red, veins in blue, and the disorganized blood vessels of a brain tumor in green.

Engineering SWIR quantum dots to target tissues of interest

While the inner core of a SWIR quantum dot (SWIR-QDs) generates the unique fluorescent properties of short wave infrared light, the other critical component of the dot is the outer surface, which must be engineered to target a tissue of interest. The researchers call this “functionalization,” which means making them useful for studying specific tissues and biological processes. Bawendi and colleagues engineered three distinct types of SWIR quantum dots to demonstrate their use in studying different biological processes.
The first type of SWIR-QDs were engineered with phospholipid micelle surface coatings. Micelles are small particles that have a hydrophilic (water-loving) outer shell and a hydrophobic (water repelling) inner layer. The micelle-embedded SWIR-QDs dissolved and circulated through the bloodstream for an extended period, allowing the researchers to study heart and respiration rates in awake mice.
The advantage of these SWIR-QDs is the ability to image physiological processes that occur too rapidly to be detected by common imaging methods such as MRI or PET. This ability would allow unobtrusive monitoring of animals in their normal environment for changes in heartbeat and breathing rates during various exercise tests or in response to drug candidates for conditions such as cardiac arrhythmia.
The second type of SWIR-QDs created were embedded in chylomicrons. Chylomicrons are lipoprotein particles that consist of triglycerides, phospholipids, cholesterol, and proteins and are known to transport dietary lipids from the intestines to other locations.

These SWIR-QDs were used to study the movement and metabolism of lipids between brown adipose tissue, blood, and liver in real-time. The researchers explained that lipid-coated SWIR-QDs could be used to assess the immediate effects of medications designed to affect lipid metabolism—for example, to increase the liver’s uptake of lipids from the bloodstream of an individual with high cholesterol.

SWIR quantum dot imaging
a) Experimental set-up with lipid micelle SWIR quantum dots injected into the circulation and whole body scan with SWIR camera. b) Resulting fluorescent image shows the accumulation of the lipid micelle SWIR quantum dots in the liver (blue circle) and heart (red circle).
The third type of SWIR-QDs were composites, containing multiples QDs, and coated with PEG, which allows them to dissolve in blood. This third type was used to measure blood flow in the vasculature of the mouse brain by tracking individual SWIR-QD composite particles as they moved through the blood vessels. The researchers could view the dramatic differences between blood flow in healthy vasculature and in vessels at the margin of a brain tumor.
These SWIR-QDs would make it possible to measure blood flow in the brain before and after a stroke, and changes in response to experimental stroke medications.
“In addition to the ability to test much-needed new medications to treat stroke, the potential application to difficult-to-treat tumors is one that we are also very excited about,” said Bawendi. “We can potentially use SWIR-QDs to study how the blood flow pattern in a tumor changes over time. We could monitor disease progression or regression in response to drug treatment.

This opens a new way to assess experimental treatments for both stroke and brain cancer that have not been possible with other imaging methods.”

Source: National Institute of Biomedical Imaging and Bioengineering

Read more: Advanced quantum dots shed bright light on biological processes

University of Michigan: Nanodiscs deliver personalized cancer therapy to immune system


FDA-Has-Approved-Device-to-Combat-Drug-OverdoseResearchers at the University of Michigan have had initial success in mice using nanodiscs to deliver a customized therapeutic vaccine for the treatment of colon and melanoma cancer tumors.

“We are basically educating the immune system with these nanodiscs so that can attack cancer cells in a personalized manner,” said James Moon, the John Gideon Searle assistant professor of and biomedical engineering.

Personalized immunotherapy is a fast-growing field of research in the fight against cancer.

The therapeutic cancer vaccine employs nanodiscs loaded with tumor neoantigens, which are unique mutations found in tumor cells. By generating T-cells that recognize these specific neoantigens, the targets cancer mutations and fights to eliminate cancer cells and prevent tumor growth.

Unlike preventive vaccinations, therapeutic cancer vaccines of this type are meant to kill established cancer cells.

“The idea is that these vaccine nanodiscs will trigger the immune system to fight the existing cancer cells in a personalized manner,” Moon said.

The nanodisc technology was tested in mice with established melanoma and colon cancer tumors. After the vaccination, twenty-seven percent of T-cells in the blood of the mice in the study targeted the tumors.

When combined with immune checkpoint inhibitors, an existing technology that amplifies T-cell tumor-fighting responses, the nanodisc technology killed tumors within 10 days of treatment in the majority of the mice. After waiting 70 days, researchers then injected the same mice with the same , and the tumors were rejected by the immune system and did not grow.

“This suggests the ‘remembered’ the for long-term immunity,” said Rui Kuai, U-M doctoral student in pharmaceutical sciences and lead author of the study.

“The holy grail in is to eradicate tumors and prevent future recurrence without systemic toxicity, and our studies have produced very promising results in mice,” Moon said.

The technology is made of extremely small, synthetic high density lipoproteins measuring roughly 10 nanometers. By comparison, a human hair is 80,000 to 100,000 nanometers wide.

Drug Delivery 050815 onereallytin

“It’s a powerful vaccine technology that efficiently delivers vaccine components to the right cells in the right tissues. Better delivery translates to better T-cell responses and better efficacy,” said study co-senior author Anna Schwendeman, U-M assistant professor of pharmacy.

The next step is to test the nanodisc technology in a larger group of larger animals, Moon said.

EVOQ Therapeutics, a new U-M spinoff biotech company, has been founded to translate these results to the clinic. Lukasz Ochyl, a doctoral student in pharmaceutical sciences, is also a co-author.

The study, “Designer vaccine nanodiscs for personalized immunotherapy,” is scheduled for advance online publication Dec. 26 on the Nature Materials website.

Explore further: Fighting cancer with the power of immunity

More information: Designer vaccine nanodiscs for personalized cancer immunotherapy, Nature Materials, nature.com/articles/doi:10.1038/nmat4822