Therapeutic drugs sometimes inflict more damage than they cure. One solution to this problem is to enclose the drugs inside a capsule, shielding them from the body—and the body from them—until they can be released at just the right spot. There are lots of ways to trigger this release, including changing temperature, acidity, and exposure to magnetic fields. But triggers can come with their own risks—burns, for example. Now, researchers in California have designed what could be the most benign trigger to date: shining near-infrared light (NIR) on the encapsulated drug.
The idea of using light to liberate an encapsulated drug isn't new. Researchers around the globe have developed polymers and other materials that begin to degrade when they absorb either ultraviolet (UV) or visible light. But tissues also readily absorb UV and visible light, which means the drug release can be triggered only near the skin, where the light can reach the capsule. NIR light largely passes through tissues, so researchers have tried to use it as a trigger. But few compounds absorb NIR well and undergo chemical changes.
That changed last year when Adah Almutairi, a chemist at the University of California, San Diego, reported that she and her colleagues had designed a polymer that breaks down when it absorbs NIR light. Their polymer used a commercially available NIR-absorbing group called o-nitrobenzyl (ONB). When they catch the light, ONB groups fall off the polymer, leading to its degradation. But ONB is only a so-so NIR absorber, and it could be toxic to cells when it detaches from the polymer.
So Almutairi and her colleagues went back to the drawing board. In the 8 November issue of Macromolecules, they report creating a new material for capsules that's even better. This one is composed of a long chain of small ring-containing compounds called cresol groups strung together in a polymer. Cresol contains reactive components that make it highly unstable in its polymeric form, a feature Almutairi and her colleagues use to their advantage. After polymerizing the cresols, they cap each reactive component with a light-absorbing compound called Bhc. When the Bhcs absorb NIR light, the reactive groups are exposed and break the long polymer into two short chains. Shining additional light continues this breakdown, potentially releasing any drugs the polymer encloses. What's more, Almutairi says, Bhc is 10 times better at absorbing NIR than is ONB and is nontoxic to cells.
Yue Zhao, a chemist at the University of Sherbrooke in Quebec, Canada, calls the new approach "special chemistry" and says he suspects other drug-delivery experts will turn to the new compound for their studies. Almutairi says she and her colleagues plan to test whether the compound is useful for slowly releasing therapeutic proteins into the eye to treat macular degeneration.