Medication non-adherence remains a major challenge across nearly all diseases. To address complex medication regimens and combination therapies, researchers from Brigham and Women’s Hospital (BWH) have developed a “mini pill box” that can stay in the stomach for one week and provide a long-lasting dose of multiple medications.
In a study published online in Nature Communications in January, researchers from BWH, Massachusetts Institute of Technology and their collaborators describe success in delivering three anti-retrovirals for HIV in a pig model.
“These slow-release dosage systems can perform equal or better than the current daily doses for HIV treatment in preclinical models,” says C. Giovanni Traverso, MB, BChir, PhD, a gastroenterologist and biomedical engineer in the Division of Gastroenterology, Hepatology and Endoscopy and an Assistant Professor of Medicine at Harvard Medical School.
The team built on a design they developed in 2016 of a star-shaped structure inside a capsule. Once inside the stomach, the capsule dissolves and the star-shaped structure unfolds. Unfolded, it is too large to pass through the pylorus and exit the stomach, yet is designed to allow food to pass through the digestive system. The arms provide the rigidity and mechanical properties to withstand the compressive forces of the stomach. The polymer in the arms can be loaded with drug and allow the drug to diffuse out slowly over time. After the drug is released, the structure breaks down and is excreted.
The newly designed pill can hold multiple drugs at once, with the capacity to accommodate a different medication on each of the six arms of the star-shaped structure. The team investigated delivering the anti-retrovirals dolutegravir, rilpivirine and cabotegravir for HIV prevention among non-infected patients and for viral suppression among those infected. Researchers tested the concentration profiles for each of the doses over time in a pig model, and measured the presence of each drug in the bloodstream in the week following ingestion.
Although combination therapies have been successful in managing HIV disease and can be taken to help prevent its spread, research shows that many patients do not stick to these regimens. Studies have found that in HIV clinical trials, only about 30 percent of patients stick to their dosage plans, which makes it difficult to gather accurate data.
While this initial research focused on HIV, this novel drug-delivery system “enables the incorporation of any drug which can fit in the system,” says Dr. Traverso.
The team is now working, through a recently-formed biotechnology company, to scale and validate results from preclinical models to translate this potential therapy to patients. They are focusing on developing systems for Alzheimer’s disease, among other diseases.
“Considering GI applications may be of interest to gastroenterologists, particularly given the recognized rates of non-adherence in patients suffering from GI conditions,” Dr. Traverso adds.