Tag Archives: medical nanoparticles

Ginger nanoparticles for inflammatory bowel disease

I guess we’ll have to add ginger to the list of folk medicines (tumeric is another) which are being discovered by nanomedicine. An Aug. 17, 2016 news item on ScienceDaily describes the ‘ginger’ research at the US Dept. of Veterans Affairs,

A recent study by researchers at the Atlanta Veterans Affairs Medical Center took them to a not-so-likely destination: local farmers markets. They went in search of fresh ginger root.

Back at the lab, the scientists turned the ginger into what they are calling GDNPs, or ginger-derived nanoparticles. The process started simply enough, with your basic kitchen blender. But then it involved super-high-speed centrifuging and ultrasonic dispersion of the ginger juice, to break it up into single pellets. (Don’t try this at home!)

The research team, led by Dr. Didier Merlin with VA and the Institute for Biomedical Sciences at Georgia State University, believes the particles may be good medicine for Crohn’s disease and ulcerative colitis, the two main forms of inflammatory bowel disease (IBD). The particles may also help fight cancer linked to colitis, the scientists believe.

An Aug. 16, 2016 US Dept. of Veterans Affairs news release (also on EurekAlert), which originated the news item, provides more detail about the research,

Each ginger-based nanoparticle was about 230 nanometers in diameter. More than 300 of them could fit across the width of a human hair.

Fed to lab mice, the particles appeared to be nontoxic and had significant therapeutic effects:

  • Importantly, they efficiently targeted the colon. They were absorbed mainly by cells in the lining of the intestines, where IBD inflammation occurs.
  • The particles reduced acute colitis and prevented chronic colitis and colitis-associated cancer.
  • They enhanced intestinal repair. Specifically, they boosted the survival and proliferation of the cells that make up the lining of the colon. They also lowered the production of proteins that promote inflammation, and raised the levels of proteins that fight inflammation.

Part of the therapeutic effect, say the researchers, comes from the high levels of lipids–fatty molecules–in the particles, a result of the natural lipids in the ginger plant. One of the lipids is phosphatidic acid, an important building block of cell membranes.

The particles also retained key active constituents found naturally in ginger, such as 6-gingerol and 6-shogaol. Past lab studies have shown the compounds to be active against oxidation, inflammation, and cancer. They are what make standard ginger an effective remedy for nausea and other digestion problems. Traditional cultures have used ginger medicinally for centuries, and health food stores carry ginger-based supplements–such as chews, or the herb mixed with honey in a syrup–as digestive aids.

Delivering these compounds in a nanoparticle, says Merlin’s team, may be a more effective way to target colon tissue than simply providing the herb as a food or supplement.

The idea of fighting IBD with nanoparticles is not new. In recent years, Merlin’s lab and others have explored how to deliver conventional drugs via nanotechnology. Some of this research is promising. The approach may allow low doses of drugs to be delivered only where they are needed–inflamed tissue in the colon–and thus avoid unwanted systemic effects.

The advantage of ginger, say the researchers, is that it’s nontoxic, and could represent a very cost-effective source of medicine.

The group is looking at ginger, and other plants, as potential “nanofactories for the fabrication of medical nanoparticles.”

Merlin and his VA and Georgia State University coauthors elaborated on the idea in a report earlier this year titled “Plant-derived edible nanoparticles as a new therapeutic approach against diseases.” They wrote that plants are a “bio-renewable, sustainable, diversified platform for the production of therapeutic nanoparticles.”

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

Edible ginger-derived nanoparticles: A novel therapeutic approach for the prevention and treatment of inflammatory bowel disease and colitis-associated cancer by Mingzhen Zhang, Emilie Viennois, Meena Prasad, Yunchen Zhang, Lixin Wang, Zhan Zhang, Moon Kwon Han, Bo Xiao, Changlong Xu, Shanthi Srinivasan, Didier Merlin. Biomaterials Volume 101, September 2016, Pages 321–340         doi:10.1016/j.biomaterials.2016.06.018

This paper is behind a paywall.

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

Plant derived edible nanoparticles as a new therapeutic approach against diseases by Mingzhen Zhang, Emilie Viennois, Changlong Xu, & Didier Merlin. Tissue Barriers Volume 4, 2016 – Issue 2  http://dx.doi.org/10.1080/21688370.2015.1134415 Published online: 11 Feb 2016

This paper too is behind a paywall.

How do medical nanoparticles biodegrade?

With all the excitement about nanoscale carriers for drugs that will seek out disease processes in the body while avoiding the healthy processes, there hasn’t been much talk about what happens once those carriers have fulfilled their mission. Research from the Children’s Hospital of Philadelphia (CHOP) changes that situation (from an April 28, 2014 news item on ScienceDaily),

Nanoparticles have been heralded as a potential “disruptive technology” in biomedicine, a versatile platform that could supplant conventional technologies, both as drug delivery vehicles and diagnostic tools.

First, however, researchers must demonstrate the properly timed disintegration of these extremely small structures, a process essential for their performance and their ability to be safely cleared out of a patient’s body after their job is done. A new study presents a unique method to directly measure nanoparticle degradation in real time within biological environments.

“Nanoparticles are made with very diverse designs and properties, but all of them need to be eventually eliminated from the body after they complete their task,” said cardiology researcher Michael Chorny, Ph.D., of The Children’s Hospital of Philadelphia (CHOP). “We offer a new method to analyze and characterize nanoparticle disassembly, as a necessary step in translating nanoparticles into clinical use.”

An April 28, 2014 CHOP news release on EurekAlert, which originated the news item, provides information about the particles and about their research process,

The CHOP team has long investigated biodegradable nanoparticles for medical applications. With diameters ranging from a few tens to a few hundreds of nanometers, these particles are 10 to 1000 times smaller than red blood cells (a nanometer is one millionth of a millimeter). One major challenge is to continuously monitor the fate of nanoparticles in model biological settings and in living cells without disrupting cell functions.

“Accurately measuring nanoparticle disassembly in real time directly in media of interest, such as the interior of a living cell or other types of complex biological milieu, is challenging. Our goal here was to develop such a noninvasive method providing unbiased results,” said Chorny. “These results will help researchers to customize nanoparticle formulations for specific therapeutic and diagnostic applications.”

The study team used a physical phenomenon called Förster resonance energy transfer, or FRET, as a sort of molecular ruler to measure the distance between the components of their particles.

For this, the researchers labelled their formulations with fluorescent probes exhibiting the radiationless transfer of energy, i.e., FRET, when located within the same particle. This process results in a special pattern of fluorescence, a “fingerprint” of physically intact particles, which gradually disappears as particle disassembly proceeds. This change in the nanoparticle fluorescent properties can be monitored directly without separating the particles from their environment, allowing for undistorted, continuous measurements of their integrity.

“The molecules must be very close together, just several nanometers apart, for the energy transfer to take place,” said Chorny. “The changes in the fluorescence patterns sensitively reflect the kinetics of nanoparticle disassembly. Based on these results, we can improve the particle design in order to make them safer and more effective.”

The rate of disassembly is highly relevant to specific potential applications. For instance, some nanoparticles might carry a drug intended for quick action, while others should keep the drug protected and released in a controlled fashion over time. Tailoring formulation properties for these tasks may require carefully adjusting the time frame of the nanoparticle disassembly. This is where this technique can become a valuable tool, greatly facilitating the optimization process

The researchers also share some of their results (from the news release),

In the current study, the scientists analyzed how nanoparticles disintegrated both in liquid and semi-liquid media, and in vascular cells simulating the fate of particles used to deliver therapy to injured blood vessels. “We found that disassembly is likely to occur more rapidly early in the vessel healing process and slow down later. This may have implications for the design of nanoparticles intended for targeted drug, gene or cell therapy of vascular disease,” said Chorny.

Chorny and colleagues have long studied using nanoparticles formulated as carriers delivering antiproliferative drugs and biotherapeutics to blood vessels subject to dangerous restenosis (re-blockage). Many of these studies, in the Cardiology Research laboratory of CHOP co-author Robert J. Levy, M.D., use external magnetic fields to guide iron oxide-impregnated nanoparticles to metallic arterial stents, narrow scaffolds implanted within blood vessels.

The current research, said Chorny, while immediately relevant to restenosis therapy and magnetically guided delivery, has much broader potential applications. “Nanoparticles could be formulated with contrast agents for diagnostic imaging, or could deliver anticancer drugs to a tumor,” he said. “Our measuring tool can help researchers to develop and optimize their nanomedicine formulations for a range of medical uses.”

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

Real-time analysis of composite magnetic nanoparticle disassembly in vascular cells and biomimetic media by Jillian E. Tengood, Ivan S. Alferiev, Kehan Zhang, Ilia Fishbein, Robert J. Levy, and Michael Chorny.  Proceedings of the National Academy of Sciences, published ahead of print, March 3, 2014, in March 18, 2014 print issue. 27, 2014. http://doi.org/10.1073/pnas.1324104111

This paper is behind a paywall.