KILLING mosquitoes of the genus Anopheles, the sort that transmit malaria, is a serious business—so serious that some doctors would like to do it by using people as bait. Their idea is to dose those in malarious areas with a drug called ivermectin. This will not protect the dosees directly, for it does not act on the parasite that causes the disease. But it may protect them indirectly, by making their blood poisonous to Anopheles. Mosquitoes do not tend to fly far from the place they hatch, and experiments suggest that if most of a village’s inhabitants were to take ivermectin they could collectively do serious damage to the local Anopheles population. That would substantially reduce the number of cases of malaria in an area.
Whether this is ethical is debated. Ivermectin is used routinely to treat filariasis, river blindness, scabies and several other diseases. But drugging healthy people is generally frowned on. At the moment, though, there is a more practical objection. Ivermectin does not hang around in the body long enough to make a concerted anti-mosquito campaign that relies on it look like a realistic proposition. And it is this that Robert Langer of the Massachusetts Institute of Technology and Giovanni Traverso at Brigham and Women’s Hospital, in Boston, hope to change. As they report in Science Translational Medicine, they think they have devised a means to keep ivermectin concentrations in the blood at mosquito-killing levels for far longer than has previously been possible.
The starting point for their device is a material called poly E-caprolactone (PCL). They melted this and blended it with powdered ivermectin. Then they tested the resulting composite in an acidic solution intended to mimic conditions found in the human stomach, to see how well it protected the drug, and also the rate at which ivermectin migrated out of it. They found that the PCL did indeed protect the ivermectin from the acid. It also let the drug diffuse out steadily over the course of 14 days.
Encouraged by this finding, the two researchers pondered how to arrange for a block of ivermectin-doped PCL to stay in the stomach that long, rather than passing through to the intestine and thence, ultimately, to the outside world. Their solution was a star-shaped structure 4cm across (see picture) with a flexible polyurethane core and arms made of ivermectin-laden PCL.
For delivery, this is folded up inside a gelatine capsule, so that it can be swallowed. Once it arrives in the stomach, the gelatine is rapidly digested and the star unfolds into something large enough to avoid being expelled into the intestine, but insubstantial enough not to obstruct the passage of semi-digested food through the alimentary canal. After careful experiment, the researchers came up with an ivermectin-PCL mixture that disintegrates as it gives up its payload. Once the arms, which are made of this mixture, have dissolved, the core is small enough to pass to the intestine and out of the body.
Laboratory tests suggested this arrangement would work, so the researchers tried it out on animals—specifically, a dozen Yorkshire pigs. These are a common breed, and the passages between their stomachs and their intestines are similar in size to those of people.
Using X-rays, they monitored the stars’ movements through the pigs’ guts. They also sampled the animals’ blood, to work out how much ivermectin was getting into it. As they had hoped, the stars were able to release mosquito-killing doses of ivermectin for up to two weeks. And, as intended, when their payloads were expended they collapsed and passed safely through the remainder of the digestive system without causing any obvious ill effects.
Dr Langer and Dr Traverso hope to start human trials next year. But they also wonder if they have come up with something that might be more widely deployed. Taking repeated doses of any drug to keep its level up is a faff. If the stars could be impregnated with other drugs, then things now requiring daily or more frequent doses might be delivered on a one-horse-pill-per-fortnight basis. That would almost certainly improve compliance.
Which, if any, other drugs might be delivered in this way remains to be seen. But, even if the stars work only for ivermectin (assuming they do), they will still be a useful addition to the armoury being deployed against malaria. And that, alone, could save many lives a year.