Artificial DNA Designed to Control Drug Delivery

Different kinds of nanoparticles are bound together by DNA fragments and released at specific times. (Ceren Kimna, Technical University of Munich)

28 June 2019. Researchers in Germany are developing techniques with artificial DNA and hydrogel designed to control the sequence of drugs delivered into the body. The authors from Technical University of Munich describe their techniques and results in today’s issue of the Journal of Controlled Release (paid subscription required).

The team of Munich bio-mechanics engineering professor Oliver Lieleg and doctoral candidate Ceren Kimna are seeking better methods for delivery of drugs in patients that need to be taken at certain times or in a specific order. Adherence to medications can be difficult for people with chronic diseases where compliance with taking the drugs is important for the drugs to be effective. That problem is compounded when the drugs must be taken on a strict schedule or in a certain sequence.

Kimna and Lieleg designed a technique for releasing three drugs in sequence. “For example,” says Lieleg in a university statement, “an ointment applied to a surgical incision could release pain medication first, followed by an anti-inflammatory drug, and then a drug to reduce swelling.” Simply combining the ingredients into an ointment, the compounds would likely be administered together rather than separately.

In this case, the Munich team tested three separate simulated drugs formulated as nanoscale particles, where one nanometer equals one billionth of a meter. And the researchers used a hydrogel, a water-based biocompatible polymer, as the delivery medium, often employed with topical medications.

To determine the order of the nanoparticles in the hydrogel, the authors use synthetic DNA. While DNA is widely known as the substance in an organism’s genetic code, the consistent chemistry of DNA makes it feasible for binding to nanoparticles in predictable ways. And when bound to nanoparticles, synthetic DNA fragments react consistently to other compounds, as well as to other types of DNA.

The researchers configured a hydrogel with layers of silver, iron oxide, and gold nanoparticles. The top layer has silver nanoparticles bound to synthetic DNA fragments. That particular DNA reacts to salt, thus the silver and DNA remain in the hydrogel until it comes in contact with a saline solution. “Because the saline solution has approximately the same salinity as the human body,” notes Kimna, “we were able to simulate conditions where the active ingredients would not be released until the medication is applied.”

In the second layer, iron oxide particles are bound to two types of synthetic DNA, connected in tandem — one linked directly to the particle, and the second DNA bound to the first DNA fragment — with neither DNA types reacting to saline solutions. However, the inside DNA linked directly to the iron oxide particle reacts to the DNA originally connected to the silver particles, and freed-up in the first layer.

Thus the interactions of those synthetic DNA fragments triggers release of the iron oxide nanoparticles, but only after the silver particles are released. And as a result, the outside DNA fragment first linked indirectly to the iron oxide particles is now freed up. This now free DNA fragment reacts chemically to the DNA linked to the gold nanoparticles, releasing the third payloads, but only after the silver and iron oxide particles are released.

The authors believe the consistency of synthetic DNA makes it possible to design autonomous, robust, and precise systems for ordered or timed delivery of drugs. And while the tests use a hydrogel in an ointment, other formulations are possible. Lieleg points out that “this principle also has the potential to be used in tablets that could release several effective ingredients in the body in a specific order.”

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