Graphene patch could help patients manage diabetes

A wearable, graphene-based patch could one day maintain healthy blood glucose levels in people by measuring the sugar in sweat and then delivering the necessary dose of a diabetes drug through the skin (Nat. Nanotech. 2016, DOI:10.1038/nnano.2016.38).

The device takes scientists a step closer to the “coveted prize” in diabetes care: a noninvasive method to monitor and control blood glucose levels, writes Richard Guyof the University of Bath in a commentary about the new work.

Currently, most diabetic patients keep track of their blood glucose levels by pricking their fingers and testing a resulting droplet of blood. For people who must monitor their levels regularly, this can be a literal pain. “There are a lot of people who don’t like sticking things in their skin,” Guy says.

About 15 years ago, the Food & Drug Administration approved a noninvasive glucose-monitoring device called the GlucoWatch Biographer. Patients wore it on their wrists, and it extracted glucose from interstitial fluid in the skin using a small current. It didn’t catch on, in part because it wasn’t user friendly, Guy tells C&EN.

For the new patch, the researchers, led by Dae-Hyeong Kim of Seoul National University, decided to detect glucose in sweat because previous studies had shown that levels of the sugar in perspiration match those in blood. Other groups have also developed devices that can analyze biomolecules in sweat (C&EN, Feb. 1, 2016, page 11).

The new device uses layers of the fluoropolymer Nafion to absorb sweat and carry it toward the device’s sensors, which are built on modified graphene. The team doped the graphene with gold atoms and functionalized it with electrochemically active materials to enable reactions needed to detect glucose.

In the patch’s glucose sensors, the enzyme glucose oxidase reacts with the sugar and produces hydrogen peroxide, which, through an electrochemical reaction, extracts current from the doped graphene. This produces an electrical signal proportional to the amount of glucose present. The patch also contains pH and temperature sensors that help ensure that the glucose sensor’s signals accurately reflect the sugar’s concentration in sweat.

When two healthy volunteers wore the patch, the measured glucose levels—including spikes after meals—matched those from a commercial glucose meter. To monitor the levels, the patch sent its sensor signals to a device that analyzed them and then wirelessly relayed the data to a smartphone.

The drug delivery half of the patch consists of an array of 1-mm-tall polymer microneedles that pierce the skin. Each needle is made from a mixture of the diabetes drug metformin and a dissolvable polymer, polyvinyl pyrrolidone. And the needles are coated with a layer of tridecanoic acid. A gold and graphene mesh sits on top of the needle array and serves as a heater that can melt the coatings.

Once the tridecanoic acid melts, the needle dissolves in the skin and releases its drug payload.

When researchers applied just the drug-delivery component to the stomachs of diabetic mice, they could deliver enough metformin to lower the animal’s elevated blood glucose levels by more than 50% in 6 hours.

Guy thinks the sensor portion of the patch is closer to real-world use than the drug-delivery component. To make the drug-delivery system practical, he says, the researchers must make the microneedle array as small as possible. That means they must find a drug that’s effective at low doses.

As for the glucose-detection half of the device, Guy wonders how often a user would have to calibrate the sensors to ensure accurate readings.

Still, he calls the patch an impressive proof of concept.

University of Bath

A step towards a Type 1 Diabetes vaccine by using nanotherapy

Two years ago, the Immunology of Diabetes Research Group at the Germans Trias i Pujol Research Institute, member of the UAB-CIE Sphere, reported a new experimental immunotherapy that prevented the onset of Type 1 Diabetes in mice predisposed to the disease. This work led to more studies with the support of the Spanish Government, Catalan Government and private patrons with a keen interest in it. Thanks to this, a new step towards the creation of a vaccine has been made, which in the medium-term could be capable of preventing and even curing the disease in humans. The article published today in the scientific journal PLOS ONE describes this new step towards the creation of a vaccine.

Initially the researchers avoided the destruction of the insulin-producing pancreatic cells (beta cells) in the body by modifying the individual’s immune cells, known as dendritic cells. This important step requires the extraction of the subjects' dendritic cells for their subsequent manipulation and re-injection. The process is complex and costly. In a new study with mice researchers have achieved the same effect with a much simpler process. Nanoparticles called liposomes are created in the laboratory; when they are introduced into the body they arrest the destruction of the beta cells and avoid Diabetes development. This technique could be a much better candidate for a human vaccine. The invention is commercially protected and an international patent has been applied for.

Droplets of fat and water which can be produced on a large scale

Liposomes have been used in several medical treatments. They are not cells, but droplets with an external fat membrane, similar to cell membranes. They can be made using a very specialized process, but one that is easy and safe and also easy to scale up.

The key: beta cells in process of natural death

To complete this study Germans Trias researchers have worked together with a ICREA group from the Catalan Institute for Nanoscience and Nanotechnology (ICN2). The ICN2 is a Severo Ochoa Centre of Research Excellence located on Universitat Autònoma de Barcelona (UAB) Campus, and its mission is to seek nanotechnology solutions to challenges in the fields of biology, energy or technology. The diameter of the liposomes created for this collaborative work is from half to one micron. They were specifically generated to imitate beta cells of the pancreas that are in the process of programmed cell death (apoptosis). As the researchers showed during the previous studies, this is the way to prevent the body from destroying the beta cells and to allow it to recuperate immunological tolerance. The Catalan researchers are the first group in the world to use liposomes that imitate naturally dying cells to fight against Diabetes. The Universities of Barcelona and Lleida also contributed to this work.

Next steps 

After showing that liposomes prevent the onset of Type 1 Diabetes in mice, the next steps are to test it in human cells in vitro, to start clinical trials on human candidates for preventive vaccination and to cure the disease by combining the vaccine with regenerative therapies. The Germans Trias Institute plans to carry out these steps with patients at the hospital and to optimise the product by dosage and guideline studies. It is also planned to optimise the product for personalization. To achieve these objectives more competitive funding will be necessary from public agencies. The group is also studying collaborations and investment opportunities from the pharmaceutical industry. Private funding continues to be important and the Germans Trias Institute is studying the possibility of organizing a local campaign.

Growing incidence and complex consequences 
Type 1 Diabetes is an illness where the body does not recognize the beta cells of the pancreas as its own and destroys them. The organ produces less and less insulin, the hormone that allows us to process the sugar we eat. Patients must prick their fingers several times a day to check blood sugar levels and inject themselves with insulin in the stomach or other parts of the body. This constant control is not always easy and having too much or too little insulin can have severe consequences. The most serious is that in the long term hyperglycaemia provokes retinal damage that can lead to blindness, renal insufficiency, destruction of nerve fibres or what is called "Diabetics Foot" where ulcers form, leading eventually to the need to amputate.

The causes of the disease are unknown, although there are both genetic and environmental factors involved. About 0.3% of the population is affected and the incidence is increasing by 3-4% a year. It usually appears in children and young adults and it is incurable. This immunotherapy presents a possible solution for Type 1 Diabetes.

Source: http://www.nanotechnologyworld.org/#!A-step-towards-a-Type-1-Diabetes-vaccine-by-using-nanotherapy/c89r/5577096b0cf293eac807083b