A customizable drug implant could help automatically deliver the right amount of drugs over time to cancer patients.
Some patients don’t take their medicine when they should, and for those with cancer the results can be devastating. Drug-infused patches and under-the-skin implants can help by delivering steady doses of drugs into the patient’s bloodstream. But different patients still respond differently to the same drug. A new customizable drug implant from engineers at the University of Texas, San Antonio (UTSA), could help.
The implant, which is the size of the tip of a ballpoint pen, would be injected near or into a tumor and deliver a steady stream of chemotherapy exactly where it’s needed, and for as long as necessary. When the drug is gone, the implant would simply dissolve. Less drug would be required, which could cut costs, and less would end up affecting other tissue, which could dramatically reduce side effects.
What’s new about the implant is the strategy the UTSA researchers are using. They employed a combination of clever geometries and carefully chosen biodegradable polymers to control the rate of drug delivery over weeks or longer.
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The researchers have developed the first prototypes and done some proof-of concept benchtop experiments. If the implants work as hoped, doctors could one day prescribe drug delivery implants tailored to each patient’s tumor, and pharmacists could 3D print the prescription on demand.
“We’re developing a drug-agnostic delivery system,” said Lyle Hood, a mechanical engineering professor at the University of Texas, San Antonio, who’s leading the team developing the implant. “We’re making the casing for a bomb, and the pharma industry is going to be developing the payload.”
Millions of cancer patients are treated with conventional chemotherapies, where patients are injected with drugs that block cancer cells’ ability to multiply. The drugs do kill most cancer cells, but they temporarily harm healthy tissues as well. This causes serious side effects, including fatigue, nausea, easy bruising, and infection.
To ease side effects, researchers are developing more drugs that knock down tumors but leave healthy tissues alone. Among them are immunotherapies, which enhance the immune system’s natural ability to find and kill cancer cells. But patients on immunotherapies must go to the clinic every week or two to receive an injection.
“They have to continuously get poked with a needle. It becomes hard for the patient,” said Priya Jain, a biomedical engineering graduate student at UTSA, who’s working with Hood developing the new implant.
To deliver a steady supply of drug to a tumor at a precise dose, the UTSA researchers are optimizing the implant’s external and internal geometry. Hood explained how geometry controls drug release rate by starting with the example of a sphere—“a tiny pearl of polymer and drug.” As the sphere biodegrades, its surface area gets smaller and smaller. Since the drug release rate is proportional to the exposed surface area, this shape would cause drug levels to drop off quickly by exponential decay –quickly at first, then slower as the sphere got smaller.
More complex geometries yield different drug delivery regiments. Consider a polymer shaped like a column with a narrow hole drilled through the middle, Hood says. Over time the outer surface area gets smaller and the inner surface area gets larger, causing the implant to release a steady stream of drug for an extended period of time before dropping off rapidly.
The choice of polymer would affect drug delivery because polymers degrade in different ways. Some degrade from outside to inside, but others degrade from all directions, Jain explained. Since the drug is released only as the polymer degrades, this controls the drug delivery rate and profile.
Jain and two UTSA undergraduates have so far used dye as a stand-in for a pharmaceutical, and showed that geometry can in fact control delivery of the dye into a solution. Together with research engineer Albert Zweiner and biomedical engineer Kreg Zimmern of the Southwest Research Institute in San Antonio, Jain and Hood chose two commonly used biodegradable polymers—polylactic acid or polycaprolactone. They infuse the molten polymer with the dye, 3D-print the implant and let it harden.
Then they place it in solution, use spectrometry to detect dye that’s dissolving into solution, and weigh the implant over time as it slowly degrades. By cross-checking these two measures, they can test if the geometry delivers its payload as predicted. So far it has.
The hardest part of the work so far has been choosing that right mix of polymers, and the right printing shape and size range, Jain said. The engineers are also experimenting with 3D bioprinters that can print molten polymers and those that can print biodegradable polymers.
“The hurdles now are to optimize the geometry for different drug release rates,” Jain said. As with other 3D printing efforts, reproducibly fabricating the small structures has also proved challenging. But that’s where the potential is. “We’re going to get cute with complicated geometries and composite structures,” Hood said.
Ultimately, the UTSA team hopes to create implants that are customized to a specific patient, drug, and disease. The implants will each have a different combination of polymer and drug, and a specific geometry to control delivery.
After they get the basic design working, the engineers plan to create implants containing two polymers infused with two different drugs. This could deliver a cocktail of drugs that are more effective in treating cancer and other disorders. A doctor could also order an immunotherapy implant combined with radiotherapy, in which a beam of radiation targets the tumor. This would represent a whole new engineering approach to precision-target drugs for cancer and other disorders.
“We’re trying to launch a new field,” Hood said.
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