Doctors often struggle to choose the best dose of a drug for each patient — the dose that worked for patient A isn’t enough for patient B, or it is way too much for patient C. The response is governed by a host of factors, including genetics, age, body size, the use of other medications, the presence of diseases and the development of drug tolerances.
Now, Stanford researchers are developing new technology to help deliver an optimal, personalized drug dose. Using their drug delivery system, they were able to automatically administer chemotherapy at the desired concentration in mice, as reported today in Nature Biomedical Engineering.
“This is the first time anyone has been able to continuously control the drug levels in the body in real time. This is a novel concept with big implications because we believe we can adapt our technology to control the levels of a wide range of drugs,” said H. Tom Soh, PhD, senior author and a Stanford professor of radiology and of electrical engineering, in a recent news release.
The new technology uses three basic elements to create a closed-loop drug delivery system that continuously monitors and adjusts the infusion rate of the drug as needed.
First, a real-time biosensor measures the concentration of the drug in the bloodstream, using molecules called aptamers that bind to a specific target. (Aptamers are like antibodies made out of nucleotides.) When the drug of interest is present in the bloodstream, the aptamers bind to the drug, change shape and cause an electrochemical signal that is detected by an electrode. The more drug present, the more aptamers bind and the larger the detected signal.
Second, a controller with sophisticated software uses this detected signal to determine the optimal drug delivery rate to maintain the desired drug concentration. Third, a programmable infusion pump delivers the drug at the rate specified by the controller.
Although the initial results are very promising, many years of additional research will be needed before the system can be tested on humans. The team also plans to make many improvements, including miniaturizing the device. Currently their system is suitable for chemotherapy drug delivery — using a biosensor the size of a microscope slide, as shown in the photograph — but it is too large to be worn by a patient for continual use.
Still, the authors believe their system could be safely used in humans in the future. They stated in the paper that it would be especially useful for the controlled delivery of chemotherapy drugs to pediatric cancer patients, who are particularly difficult to dose correctly since their drug response varies widely with age and degree of physical development.
Previously: Electroceutical pioneer tackling new challenge: Self-regulating does measurements
Photo courtesy of Soh Lab