Taking a cue from traditional Chinese medicine for transdermal insulin delivery

For people taking drugs like insulin, injections are part of their daily routines—but that route can be intimidating and painful. Taking a nod from traditional Chinese medicine, a team of researchers out of Singapore has pinpointed a way to help the skin better absorb drugs usually administered by needle. 

Researchers from Nanyang Technical University, Singapore (NTU Singapore) and the country's Agency for Science, Technology and Research (A*STAR) say they've developed a pressure device resembling a vise clamp that, when applied to a fold of skin, temporarily changes the skin barrier to form "micropores" that greatly increase its ability to absorb drugs. 

Led by Daniel Lio, the team at NTU's School of Chemical and Biomedical Engineering and A*STAR took a cue from the traditional Chinese therapy known as "tuina," wherein a doctor rubs and puts pressure on the skin before applying an ointment.

Translating that idea to a study in mice, the researchers used two magnets to apply "temporal pressure" to skin on the rodents' backs. The skin then developed micropores—about 3 micrometers in diameter—that were better able to absorb a topical drug, the researchers said. Six times more of a tested drug passed through the mouse skin with micropores than without, the study, published in the journal Science Advances, showed.

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The research team, which also included members from NTU's Lee Kong Chian School of Medicine and the Skin Research Institute of Singapore, went on to test the technique's ability to deliver insulin in mice. Insulin and nanoparticles delivered using this method were measured at molecular masses up to 20,000 daltons—40 times greater than the amount reported for other transdermal delivery methods like microneedle patches, which clock a mass of around 500 daltons, the researchers said. 

In the animal studies, the team used two magnets to apply pressure to the rodents' skin for one or five minutes, based on how fast a given drug needed to be delivered, and then applied the drug like an ointment. The drug was left on the skin for 12 hours, at which point the team imaged the skin using fluorescent microscopy to measure the amount of medication that had penetrated the organ. 

The mice with skin subjected to pressure treatment had comparable amounts of the drug in their system as those who were dosed with micro-needle patches, while those who did not receive the pressure treatment absorbed significantly less of the drug through the skin, the researchers said. 

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The team believes their pressure technique could ease the treatment burden on diabetes patients forced to inject insulin multiple times a day. Using temporal pressure to aid drug absorption through the skin would cut out the discomfort associated with needles and allow gradual release of insulin over time. Plus, it could curb the risk of hypoglycemic events, which can occur when injected insulin acts too quickly, the team added.

With a promising animal trial under their belts, the researchers have gone on to file a patent for a pressure device through NTU's enterprise company, NTUitive. They've also kick-started further experiments to hone their drug delivery technique, according to an NTU press release.