For among the powerful drugs used to fight infection and cancer, there’s only a small difference between a healing dose and a dose that is large enough to cause dangerous unintended effects. But predicting that margin is a persistent challenge because different people react in a different way to medications -; even to the identical dose.
Currently, doctors can calibrate the quantity of medication they administer partially by drawing blood to check the quantity of drugs in a patient’s body. But results from those tests often take a day to process and only measure dosage at one or two moments in time, so that they don’t help much when determining the best way to adjust dosage amounts in real time.
Now, a UCLA-led research team has developed a wearable patch that uses inexpensive microneedles to research the fluid between cells lower than a millimeter underneath the skin and repeatedly record concentrations of drugs within the body. The technology may very well be a step toward improving doctors’ ability to manage precise medication doses.
In a study published in Science Advances, the investigators tested the system in rats that had been treated with antibiotics. Using data taken by the device inside about quarter-hour after the medication was administered, the researchers reliably forecast how much of that drug could be effectively delivered to the animal’s system in total.
This biosensing microneedle technology advances many various features of personalized medicine. It might allow us to enhance treatments by optimizing the drug dosage for every individual, and it’s inexpensive, so everyone may benefit from this solution. Moreover, it could allow us to tell care by measuring not only drug molecules but additionally naturally occurring molecules within the body which are relevant to health, offering a recent format for wearable health monitoring.”
Sam Emaminejad, the paper’s senior and corresponding writer, member of the California NanoSystems Institute at UCLA
Emaminejad can also be an associate professor of electrical and computer engineering on the UCLA Samueli School of Engineering and the director of the Interconnected and Integrated Bioelectronics Lab.
The power to exactly measure drug dosage could also expand physicians’ options for treating their patients. Today, doctors shrink back from prescribing some drugs that may be highly effective at the right dose but toxic and even fatal at a dose that is too high. Enabling them to more safely administer those medicines may additionally help mitigate dangerous bacteria’s increasing resistance to antibiotics.
“The emerging microbial antibiotic resistance crisis is partially rooted in ineffective use of antibiotics, including poor decisions of medicine,” said Stanford University pediatric pulmonologist Carlos Milla, a co-author of the study. “Oftentimes that is as a consequence of the difficulties of managing essentially the most effective drugs to avoid serious toxicities. This sensor definitely opens up the possibility for excellent precision and confidence using essentially the most effective medicines.”
The patch, a few quarter-inch in diameter, detects drugs using engineered strands of DNA called aptamers. When an aptamer comes in touch with a particular goal molecule, it changes shape. Within the device, one end of the aptamers is anchored to gold nanoparticles deposited on the microneedle. The opposite end of the aptamers is attached to special molecules that produce measurable signals when the aptamers change shape.
The exposed a part of the microneedles, that are made by cutting down clinical-grade acupuncture needles, is simply about half a millimeter long.
The researchers evaluated the device in rats using three different dosages of the antibiotic tobramycin. They found that the patch’s measurements of drug concentrations correlated with those produced by conventional blood tests. The patch’s measurement of peak drug concentration within the body -; which occurs in the primary 12 to twenty minutes after a dose is run -; may very well be used to predict how much of the medication is effectively delivered to the body over the course of an hour or more.
“These experiments not only showed that our sensor readings are reliable, but additionally validated our models for correlating minimally invasive measurements to the concentration of drug circulating within the blood,” said lead writer Shuyu Lin, a former member of Emaminejad’s lab who recently earned his doctorate from UCLA.
The authors estimate that materials to supply the patch would cost lower than $2 per unit, suggesting that it may very well be manufactured cost-effectively on a big scale. Future studies will deal with optimizing the patch and further analyzing its safety, before it moves to clinical trials. That research can be funded partially by a grant from CNSI’s Noble Family Innovation Fund.
The opposite lead authors of the paper are UCLA graduate students Xuanbing Cheng and Jialun Zhu, also from Emaminejad’s lab. Other UCLA authors are former postdoctoral researchers Bo Wang and Yichao Zhao; graduate students Tsung-Yu Wu, Jiawei Tan and Wenzhong Yan; undergraduates Justin Yeung and Sarah Forman; research associate David Jelinek; Abraham Horrillo, who recently earned a bachelor’s degree; and Hilary Coller, a professor of molecular, cell and developmental biology and of biological chemistry.
The study was supported by the National Science Foundation, the Brain & Behavior Foundation, the Melanoma Research Alliance and the UCLA Innovation Fund.
Source:
California NanoSystems Institute
Journal reference:
Lin, S., et al. (2022) Wearable microneedle-based electrochemical aptamer biosensing for precision dosing of medicine with narrow therapeutic windows. Science Advances. doi.org/10.1126/sciadv.abq4539.