World first for clinical trial of skin patch to monitor therapeutic drugs in real time

The world’s first clinical trial of a sensor that can monitor drug concentrations in a patient in real time has reported back. The small-scale clinical trial used patches that accurately recorded the concentration of the antibiotic vancomycin in the dermal interstitial fluid at five-minute intervals. This technology could soon be helping doctors monitor drug levels in a patient to prevent serious side-effects.

Researchers have developed electronic aptamer sensors for the continuous monitoring of a variety of molecules in body fluids. Aptamers, the DNA equivalent of antibodies, can be produced to specifically recognise any small molecule target. In combination with an electronic readout mechanism for this binding event, this has enabled the laboratory of Kevin Plaxco at the University of California, Santa Barbara to develop a general platform that can be used to detect any small molecule in serum.

Applying the platform to monitor a target molecule continuously in the bloodstream has proven more challenging, however. In 2017, the researchers succeeded in implanting sensors into live rats to monitor levels of the cancer drug doxyrubicin or the antibiotic kanamycin, while the rats moved around normally.¹ After multiple other studies with sensors against dozens of different molecules, of which more than a dozen were tested in animal experiments, Plaxco’s team has now moved a step closer to the ultimate goal of using it in personalised medicine for human patients.² Working with the clinical research group of Sophie Stocker at the University of Sydney, Australia, Plaxco and colleagues at the Australian company Nutromics have reported the completion of the first clinical trial of electrochemical aptamer sensors used for the continuous monitoring of a drug molecule in situ in humans.

The trial used a novel, wearable skin patch that contained the electronics. The sensors, which are on minimally-invasive, 3mm-long needles integrated into the patch, penetrate the skin and perform measurements in the dermal interstitial fluid, found between skin cells and blood vessels. They were used to monitor the concentration of vancomycin, an important antibiotic that is difficult to dose and can lead to kidney damage in excess. ‘Although driven by distinctly different – and more easily generalisable – chemistry, the form factor of the patches closely resembles that of the continuous glucose monitors that many people with diabetes employ to measure their blood sugar,’ Plaxco says.

The trial was conducted with six healthy participants and also involved blood samples being taken to verify that the results from the skin patches reflected drug concentrations in the blood. Overall, the results show that the patches were well tolerated and suitable for continuously monitoring the physiological concentrations of dosage-sensitive drugs such as vancomycin.

The authors note that further clinical studies will be needed with a wider range of patients to clear the path for this technology before it can be used in personalised medicine. ‘Since submitting that work, we have expanded the clinical trials to nearly 100 people, including a few dozen ICU patients, all in support of applying for [US Food and Drug Administration] approval prior to product launch in late 2027,’ Plaxco tells Chemistry World.

Georg Hoffmann, founder and director of Trillium, a company specialising in medical diagnostics, welcomed the research calling it ‘an exciting advancement in the field of therapeutic drug monitoring’. He also cautioned that ‘we must not underestimate the substantial clinical evaluation effort that lies ahead. In rigorous, large-scale studies, questions about sensor durability, calibration stability, interference from other medications and performance across varying physiological conditions must all be systematically addressed. The road from promising early trial to robust clinical tool is long, but this initial work provides an encouraging foundation.’