Tag Archives: drug delivery

Researching a curcumin delivery system—a nutraceutical story

A Nov. 6, 2014 news item on ScienceDaily features research on delivering curcumin’s (a constituent of turmeric) health benefits more efficiently (there is a twist; for the impatient, you may want to scroll down to where I provide an excerpt from the university’s news release) from Ohio State University (US),

The health benefits of over-the-counter curcumin supplements might not get past your gut, but new research shows that a modified formulation of the spice releases its anti-inflammatory goodness throughout the body.

Curcumin is a naturally occurring compound found in the spice turmeric that has been used for centuries as an Ayurvedic medicine treatment for such ailments as allergies, diabetes and ulcers.

Anecdotal and scientific evidence suggests curcumin promotes health because it lowers inflammation, but it is not absorbed well by the body. Most curcumin in food or supplements stays in the gastrointestinal tract, and any portion that’s absorbed is metabolized quickly.

A Nov. 6, 2014 Ohio State University news release by Emily Caldwell (also on EurekAlert), which originated the news item, explains the interest in curcumin in more detail and describes the research in more detail,

Many research groups are testing the compound’s effects on disorders ranging from colon cancer to osteoarthritis. Others, like these Ohio State University scientists, are investigating whether enabling widespread availability of curcumin’s biological effects to the entire body could make it useful both therapeutically and as a daily supplement to combat disease.

“There’s a reason why this compound has been used for hundreds of years in Eastern medicine. And this study suggests that we have identified a better and more effective way to deliver curcumin and know what diseases to use it for so that we can take advantage of its anti-inflammatory power,” said Nicholas Young, a postdoctoral researcher in rheumatology and immunology at Ohio State and lead author of the study.

Curcumin powder was mixed with castor oil and polyethylene glycol in a process called nano-emulsion (think vinaigrette salad dressing), creating fluid teeming with microvesicles that contain curcumin. This process allows the compound to dissolve and be more easily absorbed by the gut to enter the bloodstream and tissues.

Feeding mice this curcumin-based drug shut down an acute inflammatory reaction by blocking activation of a key protein that triggers the immune response. The researchers were also the first to show that curcumin stops recruitment of specific immune cells that, when overactive, are linked to such problems as heart disease and obesity.

Young and his colleagues, including co-senior authors Lai-Chu Wu and Wael Jarjour of the Division of Rheumatology and Immunology at Ohio State’s Wexner Medical Center, now want to know if curcumin in this form can counter the chronic inflammation that is linked to sickness and age-related frailty. They have started with animal studies testing nano-emulsified curcumin’s ability to prevent or control inflammation in a lupus model.

“We envision that this nutraceutical could be used one day both as a daily supplement to help prevent certain diseases and as a therapeutic drug to help combat the bad inflammation observed in many diseases,” Young said. “The distinction will then be in the amount given – perhaps a low dose for daily prevention and higher doses for disease suppression.”

The term nutraceutical refers to foods or nutrients that provide medical or health benefits.

This news release notes the latest research is built on previous work,

The curcumin delivery system was created in Ohio State’s College of Pharmacy, and these researchers previously showed that concentrations of the emulsified curcumin in blood were more than 10 times higher than of curcumin powder suspended in water.

A more precise description of the current research is then provided (from the news release),

… From there, the researchers launched experiments in mice and cell cultures, generating artificial inflammation and comparing the effects of the nano-emulsified curcumin with the effects of curcumin powder in water or no treatment at all. [emphasis mine]

The researchers injected mice with lipopolysaccharide, a bacteria cell wall extract that stimulates an immune reaction in animals. Curcumin can target many molecules, but the research team zeroed in on NF-kB, a protein that is known to play an important role in the immune response.

In a specialized imaging machine, mice receiving plain curcumin lit up with bioluminescent signals indicating that NF-kB was actively triggering an immune response, while mice receiving nano-emulsified curcumin showed minimal signs – a 22-fold reduction – that the protein had been activated at all.

Knowing that curcumin delivered in this way could shut down NF-kB activation throughout the animals’ bodies, researchers looked for further details about the compound’s effects on inflammation. They found that nano-emulsified curcumin halted the recruitment of immune cells called macrophages that “eat” invading pathogens but also contribute to inflammation by secreting pro-inflammatory chemicals. And in cells isolated from human blood samples, macrophages were stopped in their tracks.

“This macrophage-specific effect of curcumin had not been described before,” Young said. “Because of that finding, we propose nano-emulsified curcumin has the best potential against macrophage-associated inflammation.”

Inflammation triggered by overactive macrophages has been linked to cardiovascular disease, disorders that accompany obesity, Crohn’s disease, rheumatoid arthritis, inflammatory bowel disease, diabetes and lupus-related nephritis.

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

Oral Administration of Nano-Emulsion Curcumin in Mice Suppresses Inflammatory-Induced NFκB Signaling and Macrophage Migration by Nicholas A. Young, Michael S. Bruss, Mark Gardner, William L. Willis, Xiaokui Mo, Giancarlo R. Valiente, Yu Cao, Zhongfa Liu, Wael N. Jarjour, and Lai-Chu Wu. PLOS ONE Published: November 04, 2014 DOI: 10.1371/journal.pone.0111559

This paper is open accesss.

I have an Oct. 1, 2014 posting which features research on curcumin for healing wounds and on tumerone for stimulating the formation of stem cells in the brain.

No need for eye drops when your contact lenses can dispense your eye medication

Anyone who has difficulty getting or allowing drops into their eyes (I once slid out of an ophthalmologist’s examination chair trying to avoid the eye drops he was administering at the end of my appointment) is going appreciate this Dec. 9, 2013 news item on Nanowerk,

For nearly half a century, contact lenses have been proposed as a means of ocular drug delivery that may someday replace eye drops, but achieving controlled drug release has been a significant challenge. Researchers at Massachusetts Eye and Ear/Harvard Medical School Department of Ophthalmology, Boston Children’s Hospital, and the Massachusetts Institute of Technology are one step closer to an eye drop-free reality with the development of a drug-eluting contact lens designed for prolonged delivery of latanoprost, a common drug used for the treatment of glaucoma, the leading cause of irreversible blindness worldwide.

The Dec. 9, 2013 Massachusetts Eye and Ear Infirmary press release (also on EurekAlert), which originated the news item, notes that a lot of people have problems with eye drops and gives a general description of the research,

“In general, eye drops are an inefficient method of drug delivery that has notoriously poor patient adherence. This contact lens design can potentially be used as a treatment for glaucoma and as a platform for other ocular drug delivery applications,” said Joseph Ciolino, M.D, Mass. Eye and Ear cornea specialist and lead author of the paper.

The contacts were designed with materials that are FDA-approved for use on the eye. The latanoprost-eluting contact lenses were created by encapsulating latanoprost-polymer films in commonly used contact lens hydrogel. Their findings are described online and will be in the January 2014 printed issue of Biomaterials.

“The lens we have developed is capable of delivering large amounts of drug at substantially constant rates over weeks to months,” said Professor Daniel Kohane, director of the Laboratory for Biomaterials and Drug Delivery at Boston Children’s Hospital.

In vivo, single contact lenses were able to achieve, for one month, latanoprost concentrations in the aqueous humor that were comparable to those achieved with daily topical latanoprost solution, the current first-line treatment for glaucoma.

The lenses appeared safe in cell culture and animal studies. This is the first contact lens that has been shown to release drugs for this long in animal models.

The newly designed contact lens has a clear central aperture and contains a drug-polymer film in the periphery, which helps to control drug release. The lenses can be made with no refractive power or with the ability to correct the refractive error in near sided or far sided eyes.

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

In vivo performance of a drug-eluting contact lens to treat glaucoma for a month by Joseph B. Ciolino, Cristina F. Stefanescu, Amy E. Ross, Borja Salvador-Culla, Priscila Cortez, Eden M. Ford, Kate A. Wymbs, Sarah L. Sprague, Daniel R. Mascoop, Shireen S. Rudina, Sunia A. Trauger, Fabiano Cade, Daniel S. Kohane. Biomaterials Volume 35, Issue 1, January 2014, Pages 432–439 DOI: S0142961213011150

This article is behind a paywall.

At the nanoscale, grapefruit swings from being medication danger to medication enhancer

It’s known that grapefruit, despite its health benefits, can inhibit (or even a pose danger) to a medication’s effectiveness. Most of us have been warned at one time or another to avoid grapefruit juice when downing a pill. So, the news from the University of Louisville (Kentucky; UofL) about grapefruit as part of a drug delivery system seems a little counter-intuitive (from the May 22, 2013 news item on Azonano),

Grapefruits have long been known for their health benefits, and the subtropical fruit may revolutionize how medical therapies like anti-cancer drugs are delivered to specific tumor cells.

University of Louisville researchers have uncovered how to create nanoparticles using natural lipids derived from grapefruit, and have discovered how to use them as drug delivery vehicles. UofL scientists Huang-Ge Zhang, D.V.M., Ph.D., Qilong Wang, Ph.D., and their team today (May 21, 2013), published their findings in Nature Communications.

The May 21, 2013 University of Louisville news release by Julie Heflin, which originated the news item, describes how the nanoparticles are derived and their advantages,

“These nanoparticles, which we’ve named grapefruit-derived nanovectors (GNVs), are derived from an edible plant, and we believe they are less toxic for patients, result in less biohazardous waste for the environment and are much cheaper to produce at large scale than nanoparticles made from synthetic materials,” said Zhang, who holds the Founders Chair in Cancer Research at the Brown Cancer Center.

The researchers demonstrated that GNVs can transport various therapeutic agents, including anti-cancer drugs, DNA/RNA and proteins such as antibodies. Treatment of animals with GNVs seemed to cause less adverse effects than treatment with drugs encapsulated in synthetic lipids.

“Our GNVs can be modified to target specific cells — we can use them like missiles to carry a variety of therapeutic agents for the purpose of destroying diseased cells,” he said. “Furthermore, we can do this at an affordable price.”

The therapeutic potential of grapefruit derived nanoparticles was further validated through a Phase 1 clinical trial for treatment of colon cancer patients. So far, researchers have observed no toxicity in the patients who orally took the anti-inflammatory agent curcumin encapsulated in grapefruit nanoparticles.

The UofL scientists also plan to test whether this technology can be applied in the treatment of inflammation related autoimmune diseases like rheumatoid arthritis.

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

Delivery of therapeutic agents by nanoparticles made of grapefruit-derived lipids by Qilong Wang, Xiaoying Zhuang, Jingyao Mu, Zhong-Bin Deng, Hong Jiang, Xiaoyu Xiang, Baomei Wang, Jun Yan, Donald Miller, & Huang-Ge Zhang. Nature Communications 4, 1867 doi:10.1038/ncomms2886 Published 21 May 2013

This paper is behind a paywall.

As for the dangers of grapefruit-medication interactions, ABC (American Broadcasting Corporation) has a Nov. 26, 2012 news item featuring then new research suggesting that even more medications are affected by grapefruit/grapefruit juice than had previously been believed,

It has long been known that grapefruit juice can pose dangerous — and even deadly — risks when taken along with certain medications. Now, experts warn the list of medications that can result in these interactions is longer than many may have believed.

In a new report released Monday in the Canadian Medical Association Journal [CMAJ], researchers at the University of Western Ontario said that while 17 drugs were identified in 2008 as having the potential to cause serious problems when taken with grapefruit, this number has now grown to 43.

So how does a common breakfast fruit cause these problems? Grapefruits contain chemicals called furanocoumarins that interfere with how your body breaks down drugs before they enter the bloodstream. By preventing this normal breakdown of a drug, these chemicals in grapefruit can effectively cause a drug overdose and more severe side-effects.

Among the side effects sometimes seen with grapefruit-induced overdoses are heart rhythm problems, kidney failure, muscle breakdown, difficulty with breathing and blood clots. …

ABC provides a list of drugs that are affected by grapefruit here.

For interested parties, here’s a link to and a citation for the research on grapefruit-medication interactions,

Grapefruit–medication interactions: Forbidden fruit or avoidable consequences? by David G. Bailey, George Dresser, and J. Malcolm O. Arnold. CMAJ March 5, 2013 185:309-316; published ahead of print November 26, 2012,

This paper is behind a paywall.

I have a couple of final comments. (1) It would seem that the grapefruit’s characteristics at the macroscale are not echoed at the nanoscale. (2) Interestingly, the grapefruit nanoparticles (grapefruit nanovectors [GNVs]) are being used to encapsulate curcumin (a constituent of turmeric). I wrote about turmeric and its healing properties in a Dec. 26, 2011 posting, which features a number of links to research in this area.

Can you deflate your spike-studded balloon?

Researchers at North Carolina State University have developed a means for embedding carbon nanofiber spikes (or needles)  into an elastic-like membrane to create a studded balloon that could potentially be used for drug delivery according to a Jan. 15, 2013 news item on ScienceDailyOnline,

The research community is interested in finding new ways to deliver precise doses of drugs to specific targets, such as regions of the brain. One idea is to create balloons embedded with nanoscale spikes that are coated with the relevant drug. Theoretically, the deflated balloon could be inserted into the target area and then inflated, allowing the spikes on the balloon’s surface to pierce the surrounding cell walls and deliver the drug. The balloon could then be deflated and withdrawn.

But to test this concept, researchers first needed to develop an elastic material that is embedded with these aligned, nanoscale needles. That’s where the NC State [North Carolina State University] research team came in.

“We have now developed a way of embedding carbon nanofibers in an elastic silicone membrane and ensuring that the nanofibers are both perpendicular to the membrane’s surface and sturdy enough to impale cells,” says Dr. Anatoli Melechko, an associate professor of materials science and engineering at NC State and co-author of a paper on the work.

For some reason this description brought to mind medieval weapons of war such as this  flail (the ball

Flail-Klassischer-Flegel (Deutsch: Ein mit einem Lederriemen verzierter klassischer Flegel mit kugelförmigem Kopf und Kette als Faustriemen) Credit: Tim Avatar Bartel [downloaded from: http://en.wikipedia.org/wiki/File:Klassischer-Flegel.jpg]

Flail-Klassischer-Flegel (Deutsch: Ein mit einem Lederriemen verzierter klassischer Flegel mit kugelförmigem Kopf und Kette als Faustriemen) Credit: Tim Avatar Bartel [downloaded from: http://en.wikipedia.org/wiki/File:Klassischer-Flegel.jpg]

not the stick. There’s much more about the flail and its use as a weapon in this Wikipedia essay.

As for this nanoscaled balloon studded with carbon nanofibers, the Jan. 15, 2013 North Carolina State University news release, which originated the news item, goes on to describe the technique,

The researchers first “grew” the nanofibers on an aluminum bed, or substrate. They then added a drop of liquid silicone polymer. The polymer, nanofibers and substrate were then spun, so that centrifugal force spread the liquid polymer in a thin layer between the nanofibers – allowing the nanofibers to stick out above the surface. The polymer was then “cured,” turning the liquid polymer into a solid, elastic membrane. Researchers then dissolved the aluminum substrate, leaving the membrane embedded with the carbon nanofibers “needles.”

“This technique is relatively easy and inexpensive,” says Melechko, “so we are hoping this development will facilitate new research on targeted drug-delivery methods.”

The paper, “Transfer of Vertically Aligned Carbon Nanofibers to Polydimethylsiloxane (PDMS) while Maintaining their Alignment and Impalefection Functionality,” is published online in the journal ACS Applied Materials & Interfaces. Lead authors on the paper are Ryan Pearce, a Ph.D. student at NC State, and Justin Railsback, a former NC State student now pursuing a Ph.D. at Northwestern University. Co-authors are Melechko; Dr. Joseph Tracy, an assistant professor of materials science and engineering at NC State; Bryan Anderson and Mehmet Sarac, Ph.D. students at NC State; and Timothy McKnight of Oak Ridge National Laboratory.

It’s very interesting but I wonder how they plan to deflate the balloon and what will happen to the carbon nanofiber needles and balloon membrane after their usage?

Nano-G, obesity, market opportunities, and thoughts on perfection

A new treatment platform that addresses diabetes and/or obesity issues, Nano-G is being promoted as a “multi billion dollar opportunity.” From the April 3, 2012 news release on Business Wire,

“Nano-G fulfills the long overdue need for a rapidly self-administered, auto-injector delivered glucagon for hypoglycemia rescue and is the missing piece needed for the bi-hormonal pump and novel combination therapies for obesity,” noted Dr. Andrew Chen, LPI’s [Latitude Pharmaceuticals, Inc.] president. “With its excellent stability and regulatory familiarity, Nano-G can be rapidly commercialized under a low risk, low-cost 505(b)(2) NDA to provide important new therapeutic options for diabetes and obesity that were never before possible. We are now seeking partners to commercialize this exceptional multi billion dollar opportunity.”

I first read about Nano-G in an April 5, 2012 news item by Cameron Chai on Azonnano and being made curious checked out Latitude Pharmaceutical’s website to find this (excerpted from the home page),

LATITUDE Pharmaceuticals is a leading-edge contract research boutique that provides innovative drug formulation services to the biotech and pharmaceutical industries. Since our founding in 2003, we have serviced over 130 client companies and developed a reputation for creative approaches, reliability, rapid turnaround, client success and satisfaction.  We are formulation specialists that can tackle the tough formulation challenges of insoluble (un-dissolvable) compounds and we have the track record and experience to do this.

LATITUDE has an armamentarium of unique techniques and technologies to address problematic formulation issues such as insolubility, poor absorption, and vein irritation that are often encountered in new drug development.

Thank you, Latitude, for a new word, armamentarium. More sadly I was not able to find additional information about Nano-G. So I went back to the news release to find this,

LATITUDE Pharmaceuticals, Inc. (LPI) announced today that its scientists have developed the first ever, ready-to-inject, stable liquid glucagon formulation (Nano-G). A glucagon formulation with these properties had been a highly sought after Holy Grail of drug developers for decades.

Currently, glucagon is indicated for emergency treatment of insulin-induced hypoglycemia and as a diagnostic aid for radiological examinations. Researchers have long been interested in evaluating glucagon for hypoglycemia prevention, the bi-hormonal insulin/glucagon pump and the treatment of obesity but have been thwarted by the absence of a stable injectable glucagon formulation.

Glucagon is a notoriously insoluble and unstable molecule and is therefore provided as a dried powder. Before use, the glucagon is dissolved in an acid solution by following a cumbersome, eight-step procedure that becomes an outsized task during life-threatening hypoglycemia.

Nano-G is a pH-neutral, isotonic, detergent-free, aqueous formulation that contains only FDA-approved injectable ingredients. Results from rigorous 6-month real-time and accelerated ICH stability testing predict a 2-yr shelf-life. Nano-G is also stable at body temperature, making it highly suitable for subcutaneous infusion pump delivery.

Elsewhere in the news release, it’s noted that Nano-G is based on the company’s ‘Nano-E injectable nanoemulsion drug delivery program.’ The company doesn’t offer much in the way of technical detail, from the Proprietary Formulation Platform Technologies page,

These innovative dosage forms, which have patents pending, may solve your formulation challenges as well as provide new IP for your API and include:

  • Sustained release oral dosage forms (ALLDay, Minspheres, and others)
  • Bioavailability enhancing oral dosage forms for insoluble drugs
  • Injectable emulsions for low solubility, high drug load compounds (Nano-E)
  • Injectable emulsions that reduce vein irritation (Nano-E)
  • Stability enhancing and lyophilizable formulations
  • Sustained release subcutaneous and subdermal depots (PG Depot)
  • Fast drying, non-irritating adhesive gels for transdermal delivery (GelPatch)

It occurred to me while reading the news release that not only is obesity very big business as governments in Canada, the US, and elsewhere pour money into obesity research but it’s one more target in this war we’ve declared on human imperfection. Increasingly it seems that we (governments, corporations, and other formal and informal institutions) are pressed to remain youthful forever, demonstrate socially approved personality traits (shyness, begone!), maintain the ‘right’ weight, etc. as we relentlessly pursue a vision of perfection that remains always just beyond grasp.

In the meantime, I expect for those who suffer from diabetes, the news about Nano-G is promising.

Nanotechnology dieting; snowflakes; nano haiku

It’s a bit disconcerting to read about a new drug delivery system using silicon, a substance I strongly associate with computers. From the news item on Azonano,

Different types of drug molecules can be bound to the porous structure of silicon, thereby making it possible to alter their properties and control their behaviour within the body.

Porous silicon can be produced as both micro- and nanoparticles, which facilitates the introduction of the material through different dosing routes – orally, as injections or subcutaneous applications. Furthermore, biodegradable nanoparticles can be used for drug targeting.

Scientists in Finland are working on this project and possible applications include dieting. Apparently peptides which control appetite can be targeted with this new delivery system. I suspect that if this is possible there will be a stampede to use silicon drug delivery systems and public concerns about risk will be left far behind as people chase the dream of dieting without effort.

The NISE (Nanoscale Informal Science Education) Network has included some timely information about snowflakes and nanotechnology it its latest newsletter. The downloadable  education programme is here. The snowflake images are supplied by Kenneth Libbrecht, Caltech and you can see more of those here. The haiku in this month’s newsletter is,

Nano, oh nano
With surface area so
Small, but big impact

This week will be short as I’m not sure if I’ll be posting after tomorrow. Changes are afoot.

Einstein’s ghosts and a nano education programme in Europe

He named it ‘spooky action’ as the concept so unnerved him. Einstein used it to describe distant particles’ communication with each other. Today, scientists at Bristol University and the Imperial College London are using ‘spooky action’ to solve the problem of identifying quantum devices. As to why this might be useful, (from the article),

Anthony Laing, PhD student in the Department of Physics, who performed the study, said: “Apart from providing insight into the fundamentals of quantum physics, this work may be crucial for future quantum technologies.

“How else could a future quantum engineer build a quantum computer if they can’t tell which circuits they have?”

The European Commission has awarded a 1.5M Euros education contract to Israel’s Organization for Rehabilitation and Training. 30,000 European students (11 – 18 years [additional programmes for young adults 19 – 25] will be introduced to nanotechnology through the NANOYOU project. There’s more information here and here.

I’ve been wondering when they’d find a way to fuse nanotechnology with sex and they’ve done it. Apparently nanotechnology may be helpful for erectile dysfunction. There’s a project which focuses on drug delivery and has been tested on rats. So I don’t think there’s anything to get too excited about yet but if you are interested, there’s more here.