Tag Archives: obesity

Melting body fat with a microneedle patch

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For many people this may seem like a dream come true but there is a proviso. So far researchers have gotten to the in vivo testing (mice)  with no word about human clinical trials, which means it could be quite a while, assuming human clinical trials go well, before any product comes to market. With that in mind, here’s more from a Sept.15, 2017 news item on Nanowerk,

Researchers have devised a medicated skin patch that can turn energy-storing white fat into energy-burning brown fat locally while raising the body’s overall metabolism. The patch could be used to burn off pockets of unwanted fat such as “love handles” and treat metabolic disorders like obesity and diabetes, according to researchers at Columbia University Medical Center (CUMC) and the University of North Carolina.

A Sept. 15, 2017 Columbia University Medical Center news release on EurekAlert, which originated the news item, describes the research further,

Humans have two types of fat. White fat stores excess energy in large triglyceride droplets. Brown fat has smaller droplets and a high number of mitochondria that burn fat to produce heat. Newborns have a relative abundance of brown fat, which protects against exposure to cold temperatures. But by adulthood, most brown fat is lost.

For years, researchers have been searching for therapies that can transform an adult’s white fat into brown fat–a process named browning–which can happen naturally when the body is exposed to cold temperatures–as a treatment for obesity and diabetes.

“There are several clinically available drugs that promote browning, but all must be given as pills or injections,” said study co-leader Li Qiang, PhD, assistant professor of pathology and cell biology at CUMC. “This exposes the whole body to the drugs, which can lead to side effects such as stomach upset, weight gain, and bone fractures. Our skin patch appears to alleviate these complications by delivering most drugs directly to fat tissue.”

To apply the treatment, the drugs are first encased in nanoparticles, each roughly 250 nanometers (nm) in diameter–too small to be seen by the naked eye. (In comparison, a human hair is about 100,000 nm wide.) The nanoparticles are then loaded into a centimeter-square skin patch containing dozens of microscopic needles. When applied to skin, the needles painlessly pierce the skin and gradually release the drug from nanoparticles into underlying tissue.

“The nanoparticles were designed to effectively hold the drug and then gradually collapse, releasing it into nearby tissue in a sustained way instead of spreading the drug throughout the body quickly,” said patch designer and study co-leader Zhen Gu, PhD, associate professor of joint biomedical engineering at the University of North Carolina at Chapel Hill and North Carolina State University.

The new treatment approach was tested in obese mice by loading the nanoparticles with one of two compounds known to promote browning: rosiglitazone (Avandia) or beta-adrenergic receptor agonist (CL 316243) that works well in mice but not in humans. Each mouse was given two patches–one loaded with drug-containing nanoparticles and another without drug–that were placed on either side of the lower abdomen. New patches were applied every three days for a total of four weeks. Control mice were also given two empty patches.

Mice treated with either of the two drugs had a 20 percent reduction in fat on the treated side compared to the untreated side. They also had significantly lower fasting blood glucose levels than untreated mice.

Tests in normal, lean mice revealed that treatment with either of the two drugs increased the animals’ oxygen consumption (a measure of overall metabolic activity) by about 20 percent compared to untreated controls.

Genetic analyses revealed that the treated side contained more genes associated with brown fat than on the untreated side, suggesting that the observed metabolic changes and fat reduction were due to an increase in browning in the treated mice.

“Many people will no doubt be excited to learn that we may be able to offer a noninvasive alternative to liposuction for reducing love handles,” says Dr. Qiang. “What’s much more important is that our patch may provide a safe and effective means of treating obesity and related metabolic disorders such as diabetes.” [emphasis mine]

The patch has not been tested in humans. The researchers are currently studying which drugs, or combination of drugs, work best to promote localized browning and increase overall metabolism.

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The study was supported by grants from the North Carolina Translational and Clinical Sciences Institute and the National Institutes of Health (1UL1TR001111, R00DK97455, and P30DK063608).

Notice the emphasis on health and that the funding does not seem to be from industry (the National Institutes of Health is definitely a federal US agency but I’m not familiar with the North Carolina Translational and Clinical Sciences Institute).

Getting back to the research, here’s an animation featuring the work,

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

Locally Induced Adipose Tissue Browning by Microneedle Patch for Obesity Treatment by Yuqi Zhang†, Qiongming Liu, Jicheng Yu†, Shuangjiang Yu, Jinqiang Wang, Li Qiang, and Zhen Gu. ACS Nano, Article ASAP DOI: 10.1021/acsnano.7b04348 Publication Date (Web): September 15, 2017

Copyright © 2017 American Chemical Society

This paper is behind a paywall.

I would imagine that Qiang and his colleagues will find a number of business entities will be lining up to fund their work. While the researchers may be focused primarily on health issues, I imagine business types will be seeing dollar signs (very big ones with many zeroes).

Could engineered nanoparticles be behind rise in obesity and metabolic disorders?

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The researchers haven’t published a study and they have used fruit flies as their testing mechanism (animal models) so, it’s a little difficult (futile) to analyze the work at this stage but it is intriguing. A June 9, 2015 news item on Azonano announces a research collaboration  designed to examine the impact engineered nanoparticles have on the gut and the gut microbiome,

Researchers at Binghamton University believe understanding nano particles’ ability to influence our metabolic processing may be integral to mediating metabolic disorders and obesity, both of which are on the rise and have been linked to processed foods.

Anthony Fiumera, associate professor of biological sciences, and Gretchen Mahler, assistant professor of biomedical engineering, are collaborating on a research project funded by a Binghamton University Transdisciplinary Areas of Excellence (TAE) grant to discover the role ingested nanoparticles play in the physiology and function of the gut and gut microbiome.

A June 8, 2015 Binghamton University news release, which originated the news item, describes the reasoning behind the research,

The gut microbiome is the population of microbes living within the human intestine, consisting of tens of trillions of microorganisms (including at least 1,000 different species of known bacteria). Nanoparticles, which are often added to processed foods to enhance texture and color, have been linked to changes in gut function. As processed foods become more common elements of our diet, there has been a significant increase in concentrations of these particles found in the human body.

Fiumera works in vivo with fruit flies while Mahler works in vitro using a 3-D cell-culture model of the gastrointestinal (GI) tract to understand how ingesting nanoparticles influences glucose processing and the gut microbiome. By using complementary research methods, the researchers have helped advance each other’s understanding of nanoparticles.

Using fruit flies, Fiumera looks at the effects of nanoparticles on development, physiology and biochemical composition, as well as the microbial community in the GI tract of the fly. The fly model offers two advantages: 1) research can be done on a wide range of traits that might be altered by changes in metabolism and 2) the metabolic processes within the fly are similar to those in humans. Fiumera also aims to investigate which genes are associated with responses to the nanoparticles, which ultimately may help us understand why individuals react differently to nanoparticles.

For this project, Mahler expanded her GI tract model to include a commensal intestinal bacterial species and used the model to determine a more detailed mechanism of the role of nanoparticle exposure on gut bacteria and intestinal function. Early results have shown that nanoparticle ingestion alters glucose absorption, and that the presence of beneficial gut bacteria eliminates these effects.

Mahler was already investigating nanoparticles when she reached out to Fiumera and proposed they combine their respective expertise. With the help of undergraduate students Gabriella Shull and John Fountain and graduate student Jonathan Richter, Fiumera and Mahler have begun to uncover some effects of ingesting nanoparticles. Since they are using realistic, low concentrations of nanoparticles, the effects are slight, but eventually may be additive.

The most interesting aspect of this research (to me) is the notion that the impact may be additive. In short, you might be able to tolerate a few more nanoparticles in your gut but as more engineered nanoparticles become part of our food and drink (including water) and your gut receives more and more that tolerance may no longer possible.

There is increasing concern about engineered nanoparticles as they cycle through environment and the US Environmental Protection Agency (EPA) funded a programed by Arizona State University (ASU), LCnano Network (part of the EPA’s larger Life Cycle of Nanomaterials project). You can find out more about the ASU program in my April 8, 2014 post (scroll down about 50% of the way).

Getting back to Binghamton, I look forward to hearing more about the research as it progresses.

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

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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.

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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.

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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.