Chen Peng, left, and Xu Chenjie with a set of microneedle patches (Nanyang Technological University, Singapore)
29 December 2017. A skin patch containing hundreds of tiny porous needles is shown in lab mice to deliver drugs that turn ordinary body fat into calorie-burning brown fat to reduce body mass. Researchers at Nanyang Technological University in Singapore describe the patch in a recent issue of the journal Small Methods (paid subscription required).
A team led by biomedical engineering professors Chen Peng and Xu Chenjie is seeking simple, safe, and effective methods to help reduce the epidemic of obesity. Overweight and obesity are worldwide problems, with World Health Organization estimating in 2016 that 1.9 billion people are overweight, with 650 million of those considered obese. And while obesity is preventable, the number of people with the condition tripled since 1975, according to WHO.
Chen and Xu focus on methods for delivering drugs that increase the amount of brown fat in the body. Babies are born with brown fat cells that keep their bodies warm by burning energy. Brown fat cells are rich in mitochondria, the energy producers in cells, that help burn calories to release heat. But brown fat cells disappear over time, replaced by white fat cells that store calories, which in excess lead to overweight and obesity.
The NTU team identified two drug types known to oxidize fat or help control metabolic and digestive functions. One drug type is beta3 adrenergic receptor agonists that in tests with lab mice, and in some cases humans, increase fat oxidation and energy expenditure, showing promise to help control weight. Another drug is the hormone T3 triiodothyronine, produced by the thyroid gland to help control a number of functions, including metabolism and digestion.
Both drugs are approved by FDA respectively for overactive bladder and underactive thyroid, but are also shown to convert white fat into brown fat. For these drugs, however, control of dosing, adverse side effects, and extending effectiveness over time are challenges.
To meet these issues, Chen, Xu, and colleagues devised a skin patch made with biocompatible polymers, containing hundreds of tiny porous needles, each thinner than a human hair, and loaded with one of the two drugs. The needles penetrate the outer layers of skin, enough to release the drug-laden needles, but not causing discomfort to the recipient. The patch is applied for 2 minutes, causing the needles to detach, degrade, and release their payloads.
A key feature of the patch is the ability to deliver drugs to precise locations in the body, thus reducing the amount of the compounds administered. “The amount of drugs we used in the patch,” says Xu in a university statement, “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.”
The researchers tested the patch in lab mice induced with obesity by a high-fat diet. The team reports the mice began converting white fat into brown in about 5 days. After 4 weeks, mice receiving the drug patches lost about 30 percent of their body fat, as well as showing lower levels of blood cholesterol and fatty acids than untreated mice.
“What we aim to develop,” notes Chen “is a painless patch that everyone could use easily, is unobtrusive and yet affordable.” The researchers estimate the cost to produce the patches is equivalent to $US 3.50. The university also reports the authors recently received expressions of interest from biotechnology companies, and are seeking to partner with clinical scientists to test the patch with humans.
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