Controlled time release of multiple drugs for combination therapy

Gary Boas, gboas@eggship-media.com

Combination therapy using multiple drugs has proved effective in treating a variety of diseases, but there are still hurdles to overcome. One of the most significant of these is in the timing of the release of each drug. In many cases – treatment of cancer, for example – precise timing is critical to drug efficacy.searchers develop vaccines to protect against these types of infections.

Now, an MIT group has come up with a novel way to address this issue. In an ACS Nano paper published online Dec. 16, 2008, the researchers showed that they could achieve controlled time release of DNA strands conjugated to gold nanorods. Much as with other nanoparticles used for targeted drug delivery, these nanorods release their payloads when excited with certain wavelengths of light, allowing researchers and clinicians to determine when – and where – a drug is put into play.

Researchers have reported a novel means to achieve controlled time release of multiple drugs delivered via combination therapy. They used two differently shaped nanoparticles – “nanocapsules” and “nanobones” – which melt when excited with specific wavelengths of light, thus releasing their payloads. The nanoparticles are excited by different wavelengths – 800 and 1100 nm, respectively – enabling controlled time release of the drugs.

Others have used gold nanorods for drug delivery, said Kimberly Hamad-Schifferli, senior author of the paper, but for only one drug at a time. “Nanorods of different shapes absorb light at different wavelengths, so you can use different wavelengths to excite drug A or drug B separately,” she said.

The researchers designed two shapes of nanorods, dubbed “nanobones” and “nanocapsules.” The former melt – and thus release their payloads – when exposed to 1100-nm light; the latter, when exposed to 800-nm light. The paper notes that, in theory, as many as four differently shaped particles can be used at a time, enabling the time release of up to four drugs.

Hamad-Schifferli’s group encountered a number of challenges as it developed the nanorods for use in combination therapy. Perhaps the most nettlesome was the nanorods’ surface chemistry: Synthesis of the particles results in a surface coating that hinders successful application and biocompatibility. “We had to figure out a good way to get rid of that molecule and change the surface chemistry to something biocompatible,” she said. “Once we did that, this was very straightforward.”

The authors are continuing to develop the method for use in combination therapy. Hamad-Schifferli explained that they are looking at whether they can apply it in cells. For the ACS Nano study, she said, “we just did it in a test tube.”