US researchers have developed a star-shaped long-lasting drug device that resides in the stomach and can deliver a controlled drug dose over a period of up to two weeks.
The device was created to provide sustained release of the mosquitocidal ivermectin in a pig model over 10–14 days. There was no evidence of any gastric obstruction or mucosal damage – factors that have been major obstacles to the development of prolonged gastric drug release systems in the past.
“There are drug delivery systems that can achieve long-lasting effects, but they’re all injectable or implantable, or involve some other invasive procedure,” says Andrew Bellinger, one of the lead authors from the Massachusetts Institute of Technology (MIT) in Cambridge.
“This is the first time anyone’s ever been able to make an oral pill or capsule which can be, to the patient, the same as the pill that they’ve always been taking, but which can prolong the efficacy out to a week or more.”
Presenting the research in Science Translational Medicine
(online, 16 November 2016), the team set out to design a capsule small enough to swallow but large enough to avoid being pushed into the small intestine by the muscular compressions of the stomach. To do this, they developed a star-shaped design based on drug-loaded polymer arms joined together by acid-sensitive linkers that can dissolve slowly inside the stomach. Once these are fully dissolved, the polymer components break apart and are small enough to pass out of the stomach and continue through the digestive tract.
To allow it to be ingested, the star is folded down into a gelatin capsule that dissolves within 30 minutes in the stomach, allowing the device to unfold to its star shape within the stomach. Testing the capsule design in pigs, the researchers found that on all 107 attempts, the device “deployed” into its star shape within five minutes of ingestion. They also showed that the star was able to move freely in the stomach and there was no sign of obstruction when the animals continued to eat a normal diet.
The researchers also explored the potential use of the capsule in malaria control efforts. They developed long-acting formulations for controlled release of ivermectin and incorporated them into the device. Ivermectin targets the mosquito vector that carries malaria, and has been shown to control mosquito populations when given to humans. They found that the device released a sustained dosage of ivermectin over 10–14 days and resulted in serum concentrations effective for mosquito control.
The team say their design could be valuable for use in developing countries, such as in malaria-eliminating programmes, where it could help overcome the difficulty of getting people to take medicines on a daily basis.
The technology could also help tackle poor adherence rates observed for chronic conditions in western countries to improve and reduce variability in patient outcomes. The researchers suggest that extending dosing intervals will give healthcare professionals and caregivers better scope to engage with patients about adherence too.
“Having the ability to change the interval starts to introduce the possibility of changing the framework within which we as physicians and as healthcare providers can help our patients,” says senior author Gio Traverso from the MIT. “If you convert a medication from, let’s say, twice a day to all of a sudden once a month, for example, it’s now possible and conceivable that you might call that patient once a month and say, Mr Smith, just want to check in. Have you taken your medication?”
The researchers say they have now tested their design with several different drugs. They plan to focus on applications for conditions they believe could benefit most from sustained drug delivery, such as neuropsychiatric disorders, HIV, diabetes and epilepsy, as well as in tropical diseases. The first trial in human subjects is planned for 2017.
Commenting on the study, Jayne Lawrence, chief scientist at the Royal Pharmaceutical Society, says: “Although the concept of using gastro-retentive drug delivery systems to obtain the prolonged delivery of drug is not novel, the use of star-shaped device that is retained in the stomach, releasing a drug for almost two weeks, is. It will be interesting to see if the results of human clinical trials using this device are as exciting as the results of animal studies.”