Skin patch dissolves fat, could help treat diabetes

Through lab experiments, UNC, NC State, and Columbia University researchers developed a microneedle skin patch that delivers nanoparticles full of fat-shrinking drugs to potentially treat obesity and diabetes.

Skin patch dissolves fat, could help treat diabetes click to enlarge An up-close view of the micro patch developed by Zhen Gu, PhD
Skin patch dissolves fat, could help treat diabetes click to enlarge Zhen Gu, PhD

Scientists 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, tested so far only in mice, could be used to burn off pockets of unwanted fat and treat metabolic disorders like obesity and diabetes, according to researchers at the University of North Carolina-Chapel Hill, NC State University, and Columbia University Medical Center.

The findings were published online in ACS Nano. The patch is not ready for human clinical trials.

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 to change an adult’s white fat into brown fat – a process called browning that 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 Columbia. “This exposes the whole body to the drugs, which can lead to side effects such as stomach upset, weight gain, and bone fractures.” This new skin patch appears to avoid these complications by delivering the drugs directly to fat tissue.

During experiments, the drugs were first encased in nanoparticles, each roughly 250 nanometers 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 tiny needles. When applied to skin, the needles painlessly pierce the skin and gradually release the drug from nanoparticles into underlying tissue. 

“We designed the nanoparticles 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 in the joint UNC-NC State Department of Biomedical Engineering.

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, which works well in mice but not in humans.

Zhen Gu electron micro scan patch
This is an electron microscope view of the tiny skin patch needles filled with fat-dissolving drugs.
The researchers used two patches for each mouse. One patch was loaded with drug-containing nanoparticles, and the other patch held no drugs. They placed the patches on opposite sides of the lower abdomen. New patches were applied every three days for a total of four weeks. Control mice were 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.”

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

The National Institutes of Health and the North Carolina Translational and Clinical Sciences (NC TraCS) Institute funded this work. 

The other authors are: Yuqi Zhang, Jicheng Yu, and Jinqiang Wang at UNC and NC State, Qiongming Liu at Columbia; and Shuangjiang Yu at UNC and the Changchun Institute of Applied Chemistry at the Chinese Academy of Sciences.

Media contacts:

Lucky Tran, 212-305-3689, lt2549@cumc.columbia.edu

Mark Derewicz, 984-974-1915, mark.derewicz@unchealth.unc.edu

 

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