Microcapsules

Image courtesy of Ronald Xu

& The Ohio State University

Researchers say they have developed a quick and controllable method for getting 2 or more ingredients into the same tiny drug capsule and having them mix only when triggered by a signal like vibrations or heat.

This work was inspired by the search for targeted drug delivery options to treat cancers.

The idea with this multi-ingredient capsule is that the ingredients must be mixed for the drug to work, and the mixing could be triggered in targeted areas of the body, thereby boosting drug efficiency while reducing side effects.

While the researchers found they could use their technique to create multi-ingredient microcapsules, they have not yet used it to encapsulate cancer treatments.

They described their work in Applied Physics Letters.

“One of the limitations of chemotherapy is that less than 5% of the drugs typically get to the tumor, while the rest can be absorbed by other organs,” said study author Ronald Xu, PhD, of The Ohio State University in Columbus.

He and his colleagues thought one possible way to address this problem could be to make the drugs non-toxic when injected into the body and trigger mixing that would produce a toxic product only near the tumor site.

The researchers knew that, for such drugs to work on a large scale, there must be a way to quickly, controllably, and cost-effectively produce capsules with 2 or more active ingredients. If the drugs are to be injected and spread through the body via the bloodstream, the capsules should also be small.

With that in mind, Dr Xu and his colleagues developed a device that can produce tiny capsules approximately 100 microns across with multiple inner ingredients.

The device works by funneling different ingredients through 2 inner needles. These needles run parallel to each other and are both enclosed in a larger outer needle, which contains an ingredient for making the outer shell of the capsule.

As all the ingredients exit the needles through a single nozzle, a high-speed gas forces the liquids into a narrow stream that breaks into individual droplets. An electric field stabilizes the flow so that uniform droplets are created.

Depending on the relative flow rates, each droplet may contain 2 or more smaller inner droplets made from the ingredients in the inner needles.

The researchers tested their device with colored paraffin wax—red in one needle and blue in the other. The outer shell was made from sodium alginate, a material extracted from seaweed that turned gelatinous when the droplets fell into a calcium chloride solution.

Depending on the experimental conditions, the team was able to produce between 1000 and 100,000 capsules per second, and nearly 100% of the inner liquids were incorporated into the capsules without any waste.

Once encapsulated, the 2 colors of wax did not mix because of surface tension. But the researchers found they could force the red and blue wax to merge by vibrating the capsules. The team also discovered they could release the inner droplets by dissolving the outer shell.

The key features of the new device are its high efficiency and yield, and the fact that the size of the droplets can be uniformly controlled, Dr Xu said.

He added that, by further fine-tuning the device’s operation, the team could make capsules that are 3-5 microns across, about the size of a red blood cell. The process can also be scaled up by building an array of nozzles and could be modified to encapsulate 3 or more active ingredients by adding additional inner needles.

While Dr Xu and his colleagues were motivated by drug delivery, they believe their device might also find wider use in a range of applications that require controlled reactions, such as regenerative medicine and nuclear and chemical engineering.

Microcapsules could provide targeted drug delivery