Tag Archives: liposomes

Therapeutic nanoparticles for agricultural crops

Nanoscale drug delivery systems developed by the biomedical community may prove useful to farmers. The Canadian Broadcasting Corporation (CBC) featured the story in a May 26, 2018 online news item (with audio file; Note: A link has been removed),

Thanks to a fortuitous conversation between an Israeli chemical engineer who works on medical nanotechnology and his farmer friend, there’s a new way to deliver nourishment to nutrient-starved crops.

Avi Schroeder, the chemical engineer and cancer researcher from Technion — Israel Institute of Technology asked his friend what are the major problems facing agriculture today. “He said, ‘You know Avi, one of the major issues we’re facing is that in some of the crops we try to grow, we actually have a lack of nutrients. And then we end up not growing those crops even though they’re very valuable or very important crops.'”

This problem is only going to become more acute in many regions of the world as global population approaches eight billion people.

“Feeding them with healthy food and nutritious food is becoming a major limiting factor. And … the land we can actually grow crops on are also becoming smaller and smaller in every country because people need to build houses too. So what we want is to get actually more crops per hectare.”

The way farmers currently deliver nutrients to malnourished agricultural crops is very inefficient. Much of what is added to the leaves of the plant is wasted. Most of it washes away or isn’t taken up by the plants.

If plants don’t get the nutrients they need, their leaves start to yellow, their growth becomes stunted and they don’t produce as much food as nutrient-rich crops.

“We work primarily in the field of medicine,” says Schroeder. “What we do many times is we’ll load minuscule doses of medicine into nanoparticles — we’ll inject them into the patient. And those nanoparticles will actually be able to detect the disease site inside the body. That sounded very, very similar to the problem the farmers were actually facing — how do you get a medicine into a crop or a nutrient into a crop and get it to the right region within the crop where it’s actually necessary.”

The nanoparticles Schroeder developed are tiny packages that can deliver nutrients — any nutrients — that are placed inside.

A June 6, 2018 news item on Nanowerk offers a few more details,

An innovative technology developed at the Technion [Israel Institute of Technology] could lead to significant increases in agricultural yields. Using a nanometric transport platform on plants that was previously utilized for targeted drug delivery, researchers increased the penetration rate of nutrients into the plants, from 1% to approximately 33%.

A May 27,2018 Technion press release, which originated the news item, fleshes out the details,

The technology exploits nanoscale delivery platforms which until now were used to transport drugs to specific targets in the patient’s body. The work was published in Scientific Reports and will be presented in Nature Press.

The use of the nanotechnology for targeted drug delivery has been the focus of research activity conducted at the Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies at the Wolfson Faculty of Chemical Engineering. The present research repurposes this technology for agricultural use; and is being pursued by laboratory director Prof. Avi Schroeder and graduate student Avishai Karny.

“The constant growth in the world population demands more efficient agricultural technologies, which will produce greater supplies of healthier foods and reduce environmental damage,” said Prof. Schroeder. “The present work provides a new means of delivering essential nutrients without harming the environment.”

The researchers loaded the nutrients into liposomes which are small spheres generated in the laboratory, comprised of a fatty outer layer enveloping the required nutrients. The particles are stable in the plant’s aqueous environment and can penetrate the cells. In addition, the Technion researchers can ‘program’ them to disintegrate and release the load at precisely the location and time of interest, namely, in the roots and leaves. Disintegration occurs in acidic environments or in response to an external signal, such as light waves or heat. The molecules comprising the particles are derived from soy plants and are therefore approved and safe for consumption by both humans and animals.

In the present experiment, the researchers used 100-nanometer liposomes to deliver the nutrients iron and magnesium into both young and adult tomato crops. They demonstrated that the liposomes, which were sprayed in the form of a solution onto the leaves, penetrated the leaves and reached other leaves and roots. Only when reaching the root cells did they disintegrate and release the nutrients. As said, the technology greatly increased the nutrient penetration rate.

In addition to demonstrating the effectivity of this approach as compared to the standard spray method, the researchers also assessed the regulatory limitations associated with the spread of volatile particles.

”Our engineered liposomes are only stable within a short spraying range of up to 2 meters,” explained Prof. Schroeder. “If they travel in the air beyond that distance, they break down into safe materials (phospholipids). We hope that the success of this study will expand the research and development of similar agricultural products, to increase the yield and quality of food crops.”

This is an illustration of the work,

Each liposome (light blue bubble) was loaded with iron and magnesium particles. The liposomes sprayed on the leaves, penetrated and then spread throughout the various parts of the plant and released their load within the cells. Courtesy: Technion

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

Therapeutic nanoparticles penetrate leaves and deliver nutrients to agricultural crops by Avishai Karny, Assaf Zinger, Ashima Kajal, Janna Shainsky-Roitman, & Avi Schroeder. Scientific Reportsvolume 8, Article number: 7589 (2018) DOI: https://doi.org/10.1038/s41598-018-25197-y Published 17 May 2018

This paper is open access.

Nanomedicine and an enhanced uptake of nanoparticles

It’s nice to know that a step forward has been taken with regard to improving uptake in  nanoparticle-based drug delivery (see my April 27, 2016 posting titled: How many nanoparticle-based drugs does it take to kill a cancer tumour? More than 1% for insight into the difficulties of f nanoparticle-based drug delivery systems).

Here’s the latest move forward in a March 8, 2017 news item on Nanowerk (Note: A link has been removed),

Nanotechnology has become a growing part of medical research in recent years, with scientists feverishly working to see if tiny particles could revolutionize the world of drug delivery.

But many questions remain about how to effectively transport those particles and associated drugs to cells.
In an article published today in Scientific Reports (“Enhanced cellular uptake of size-separated lipophilic silicon nanoparticles”), FSU Associate Professor of Biological Science Steven Lenhert takes a step forward in the understanding of nanoparticles and how they can best be used to deliver drugs.

After conducting a series of experiments, Lenhert and his colleagues found that it may be possible to boost the efficacy of medicine entering target cells via a nanoparticle.

A March 8, 2017 Florida State University news release by Kathleen Haughney, which originated the news item, provides more detail about the research (an international collaboration involving the University of Toronto [Canada] and the Karlsruhe Institute of Technology [Germany]),

“We can enhance how cells take them up and make more drugs more potent,” Lenhert said.

Initially, Lenhert and his colleagues from the University of Toronto and the Karlsruhe Institute of Technology  wanted to see what happened when they encapsulated silicon nanoparticles in liposomes — or small spherical sacs of molecules — and delivered them to HeLa cells, a standard cancer cell model.

The initial goal was to test the toxicity of silicon-based nanoparticles and get a better understanding of its biological activity.

Silicon is a non-toxic substance and has well-known optical properties that allow their nanostructures to appear fluorescent under an infrared camera, where tissue would be nearly transparent. Scientists believe it has enormous potential as a delivery agent for drugs as well as in medical imaging.

But there are still questions about how silicon behaves at such a small size.

“Nanoparticles change properties as they get smaller, so scientists want to understand the biological activity,” Lenhert said. “For example, how does shape and size affect toxicity?”

Scientists found that 10 out of 18 types of the particles, ranging from 1.5 nanometers to 6 nanometers, were significantly more toxic than crude mixtures of the material.

At first, scientists believed this could be a setback, but they then discovered the reason for the toxicity levels. The more toxic fragments also had enhanced cellular uptake.

That information is more valuable long term, Lenhert said, because it means they could potentially alter nanoparticles to enhance the potency of a given therapeutic.

The work also paves the way for researchers to screen libraries of nanoparticles to see how cells react.

“This is an essential step toward the discovery of novel nanotechnology based therapeutics,” Lenhert said. “There’s big potential here for new therapeutics, but we need to be able to test everything first.”

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

Enhanced cellular uptake of size-separated lipophilic silicon nanoparticles by Aubrey E. Kusi-Appiah, Melanie L. Mastronardi, Chenxi Qian, Kenneth K. Chen, Lida Ghazanfari, Plengchart Prommapan, Christian Kübel, Geoffrey A. Ozin, & Steven Lenhert. Scientific Reports 7, Article number: 43731 (2017) doi:10.1038/srep43731 Published online: 08 March 2017

This paper is open access.

Treating bacterial infections without antibiotics in Switzerland

One of the major problems in medicine is the growing tolerance to antibiotics consequently there are research teams around the world attempting to find alternatives. A team in Switzerland has proposed a new means of eliminating bacteria without inducing tolerance according to a Nov. 2, 2014 news item on ScienceDaily,

Ever since the development of penicillin almost 90 years ago, antibiotics have remained the gold standard in the treatment of bacterial infections. However, the WHO has repeatedly warned of a growing emergence of bacteria that develop antibiotic resistance. Once antibiotics do no longer protect from bacterial infection, a mere pneumonia might be fatal.

A team of international scientists has tested a novel substance, which has been developed by Eduard Babiychuk and Annette Draeger from the Institute of Anatomy, University of Bern in Switzerland. This compound constitutes a novel approach for the treatment of bacterial infections: the scientists engineered artificial nanoparticles made of lipids, “liposomes” that closely resemble the membrane of host cells. These liposomes act as decoys for bacterial toxins and so are able to sequester and neutralize them. Without toxins, the bacteria are rendered defenseless and can be eliminated by the cells of the host’s own immune system. The study will be published in Nature Biotechnology Nov 2nd [2014].

A Nov. 3, 2014 news item on startupticker.ch provides more detail about the research and the startup which will be taking the research from the lab to the marketplace,

Artificial bait for bacterial toxins

In clinical medicine, liposomes are used to deliver specific medication into the body of patients. Here, the Bernese scientists have created liposomes which attract bacterial toxins and so protect host cells from a dangerous toxin attack. “We have made an irresistible bait for bacterial toxins. The toxins are fatally attracted to the liposomes, and once they are attached, they can be eliminated easily without danger for the host cells”, says Eduard Babiychuk who directed the study. “Since the bacteria are not targeted directly, the liposomes do not promote the development of bacterial resistance”, adds Annette Draeger. Mice which were treated with the liposomes after experimental, fatal septicemia survived without additional antibiotic therapy.

Treatment developed by the Swiss start-up LASCCO

The Technology transfer organisation of the Universities of Bern, Basel and Zurich “Unitectra” has filed a patent for this compound. The liposomal treatment is being developed as a new medicine named “CAL02” by LASCCO SA, a Geneva-based biomedical company specialized in innovative technologies for diagnostics and therapeutics. The first clinical study, conducted on patients suffering from severe streptococcal pneumonia is scheduled for 2015.

“These in vivo studies strongly support our decision to conduct a first-in-human study next year in severely-ill patients with pneumococcal pneumonia” commented Samareh Azeredo da Silveira Lajaunias, Managing Director at LASCCO. “This new drug meets crucial medical needs, since virulence factors such as toxins are responsible for serious infection-related complications. These complications concern 23% of individuals affected by community-acquired pneumonia, extend hospitalisation in intensive care units, and tremendously increase the cost of care.”

A Nov. 2, 2014 LASCCO press release covers much of the same detail as the news items but is included here for completeness (i.e., my completeness issues).

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

Engineered liposomes sequester bacterial exotoxins and protect from severe invasive infections in mice by Brian D Henry, Daniel R Neill, Katrin Anne Becker, Suzanna Gore, Laura Bricio-Moreno, Regan Ziobro, Michael J Edwards, Kathrin Mühlemann, Jörg Steinmann, Burkhard Kleuser, Lukasz Japtok, Miriam Luginbühl, Heidi Wolfmeier, André Scherag, Erich Gulbins, Aras Kadioglu, Annette Draeger, & Eduard B Babiychuk. Nature Biotechnology (2014) doi:10.1038/nbt.3037 Published online 02 November 2014

This paper is behind a paywall.