One of the greatest failures in drug treatments is adherence with many patients currently being treated with several different medications at fixed intervals, which can increase the risk of doses being skipped or forgotten. Controlled drug release is a mechanism which delivers drugs with a delay after its administration, or for a prolonged period of time to a specific target in the body.

Controlled drug release presents many advantages over immediate-release formulas, however, mechanisms for controlled drug release present many hurdles, particularly where more than one active ingredient is involved.

Now, a study from researchers at the University of Munich develops artificial DNA capable of controlling the release of active ingredients from drugs. The team states their technique, which uses a combination of hydrogels and artificial DNA, releases nanoparticles in sequence under conditions similar to those in the human body. The study is published in the Journal of Controlled Release.

An aid in treatment adherence

Previous studies show the majority of medical therapies require repeat, sequential administration of medication at intervals. Typically, the patient is in charge of taking the individual drug doses, with a failure of patient compliance reducing the efficiency of the treatment.

Therefore, the development of a delivery mechanism releasing drugs in a pre-defined, time-controlled fashion is highly desired. The current study engineers a DNA-mediated release cascade which precisely controls the sequential delivery of several different nanoparticles.

The current study engineers artificial DNA to control the release of nanometer-sized silver, iron oxide, and gold particles embedded in a special gel-like substance known as a hydrogel. A spectroscopic method is used to track the exit of the particles from the gel; the particles selected have similar motion characteristics within the gel to the particles used to transport real active ingredients, whilst being easier and cheaper to make. Results show the silver particles were released first with a saline solution added to simulate the salinity of the human body.

Synthetic biology and drug release

The lab states their mesh-like synthetic DNA structure surrounding the iron oxide particles consists of two types of DNA not affected by the saline solution. Results show the iron oxide particles were only released when the first mixture of silver and synthetic DNA clusters have dissolved. Data findings show, as a result, the iron oxide particles can separate, which releases DNA fragments which in turn act as the trigger to the third DNA-nanoparticle combination.

The team surmises they have developed artificial DNA with the ability to cascade the controlled release of multiple active ingredients in a set sequence. For the future, the researchers state a similar DNA-mediated release system may lead to the development of delivery systems which minimize the possibility of pharmaceutical therapy failure due to patient non-compliance.

Source: Technical University of Munich (TUM) 

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