A new system combines a new way to deliver drugs, via a micro-needle patch, with drugs that are known to turn energy-storing white fat into energy-burning brown fat. This innovative approach developed by scientists from Nanyang Technological University, Singapore (NTU Singapore), reduced weight gain in mice on a high fat diet and their fat mass by more than 30 percent over four weeks.

A new approach to reducing bulging tummy fats has shown promise in laboratory trials. (Credit: Nanyang Technical University)

The new type of skin patch contains hundreds of micro-needles, each thinner than a human hair, which are loaded with the drug Beta-3 adrenergic receptor agonist or another drug called thyroid hormone T3 triiodothyronine.

When the patch is pressed into the skin for about two minutes, these microneedles become embedded in the skin and detach from the patch, which can then be removed. As the needles degrade, the drug molecules then slowly diffuse to the energy-storing white fat underneath the skin layer, turning them into energy-burning brown fats.

Brown fats are found in babies, and they help to keep the baby warm by burning energy. As humans grow older, the amount of brown fats lessens and is replaced with visceral white fats.

Published in the journal Small Methods by NTU professor Chen Peng and assistant professor Xu Chenjie, this approach could help to address the worldwide obesity problem without resorting to surgical operations or oral medication that could require large dosages and could have serious side effects.

“With the embedded microneedles in the skin of the mice, the surrounding fats started browning in five days, which helped to increase the energy expenditure of the mice, leading to a reduction in body fat gain,” says Xu, who focuses on research in drug-delivery systems.

“The number of drugs we used in the patch is much less than those used in oral medication or an injected dose. This lowers the drug ingredient costs while our slow-release design minimizes its side effects,” says Xu.

Obesity that results from an excessive accumulation of fat is a major health risk factor for various diseases, including heart disease, stroke, and Type 2 diabetes. The World Health Organization estimates that 1.9 billion adults in the world are overweight in 2016 with 650 million of them being obese.

“What we aim to develop is a painless patch that everyone could use easily, is unobtrusive and yet affordable,” says Chen, a biotechnology expert who researches obesity. “Most importantly, our solution aims to use a person’s own body fats to burn more energy, which is a natural process in babies.”

Under the two scientists’ guidance at NTU’s School of Chemical and Bio-medical Engineering, research fellow Dr. Aung Than conducted experiments that showed that the patch could suppress weight gain in mice that were fed a high fat diet and thus reduce their fat mass by over 30 percent over a period of four weeks.

The treated mice also had significantly lower blood cholesterol and fatty acids levels compared with the untreated mice. Being able to deliver the drug directly to the site of action is a major reason why it is less likely to have side effects than orally delivered medication.

The team estimates that their prototype patch had a material cost of about S$5 (US$3.50) to make. The patch contains beta-3 adrenergic receptor agonist combined with Hyaluronic acid, a substance naturally found in the human body and commonly used in products like skin moisturizers.

Approved by the US FDA, Beta-3 adrenergic receptor agonist is a drug used to treat overactive bladders, while T3 triiodothyronine is a thyroid hormone commonly used for medication for an underactive thyroid gland.

Both have been shown in other research studies to be able to turn white fats brown, but their use in reducing weight gain is hampered by potentially serious side effects and drug accumulation in nontargeted tissues if conventional drug-delivery routes were used, such as through oral intake.

NTU’s Lee Kong Chian School of Medicine Melvin Leow, an associate professor who was not affiliated with this study, says it is exciting to be able to tackle obesity via the browning of white fat, and the results were promising.

“These data should encourage Phase I clinical studies in humans to translate these basic science findings to the bedside, with the hope that these micro-needle patches may be developed into an established cost-effective modality for the prevention or treatment of obesity in the near future,” adds Leow, an endocrinologist.

Since the publication of the paper, the team has received keen interest from biotechnology companies and are looking to partner with clinician scientists to further their research.

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