Researchers from Brigham & Women’s Hospital and MIT teamed up to create a capsule that can hold a week’s worth of HIV drugs in one serving. Many HIV patients need to take more than one medication. The pill is designed to make it easier for these patients to stick to their dosing schedule and reduce the hassle of taking daily medication.
The capsule can be taken just once a week and will release its medication gradually over the course of the next seven days. Researchers hope that this new delivery system will improve patient’s adherence to their treatment plan. It can also be used by those who are at risk of getting HIV to help protect them from the infection.
Key highlights of the study include the following:
According to Giovanni Traverso, biomedical engineer at Brigham and Women's Hospital and research affiliate at MIT's Koch Institute for Integrative Cancer Research, adherence is one of the primary problems of treating and preventing HIV. The ability to reduce doses makes a significant impact at the patient level by improving adherence. Traverso is one of the senior authors of the study, along with Robert Langer, an MIT David H. Koch Institute Professor, which appears in the Nature Communications journal. Lead authors of the study include MIT visiting scholar Omar Adouzid and MIT postdoc Ameya Kirtane.
The technology for the capsule was developed by scientists from a biotech company based in Massachusetts called Lyndra. The company is also working on performing a clinical trial based on the new delivery system. Langer stated that the new technology and drug-delivery system is very exciting as it can help patients with HIV/AIDS as well as those with many other diseases.
Even though the death rate of HIV has significantly decreased since the 1990’s when antiretroviral therapies were first introduced, there were still 1.2 million HIV-related deaths and 2.1 million new HIV cases in 2015 alone. There have been several large clinical trials that studied the effects of antiretroviral drugs and the prevention of HIV infections among health populations with mixed results. However, one of the major obstacles that researchers found among preventative treatment is the difficulty in getting people to take their preventative medications daily.
The team at MIT and Brigham & Women’s Hospital believe that the drug delivery pill they created may help with this problem. The capsule is star-shaped and has six arms that can be filled with drugs. These arms fold inward and are enclosed in a smooth coating. When a patient swallows the capsule, the arms gradually unfold and release the drugs.
Previous studies show that these pills can remain in a person’s stomach for up to two weeks and gradually release its contents. This technology, which was founded in 2016, inspired the team to work together to find a solution for HIV drug adherence.
When the team performed their original work, the entire star-shaped pill was made from one polymer. It both provided structure to the pill while carrying the drug. Because of this, it was more difficult to design a new pill that would release the drug at varying times as any changes to the polymer might interrupt the capsule’s structural support.
To work around these problems, the researchers had to design a new pill in which the base of the star’s structure would still be as strong as a polymer but each of the six arms needed to be filled with polymers that held different drugs. This concept would make it easier to design a pill that releases its contents at different times.
Traverso stated that in a way, it’s similar to fitting an entire pillbox in one capsule. There are chambers for every day of the week in a single pill. Animal studies showed that the pill was able to successfully place itself in the stomach and release three different HIV drugs over the course of a week. The researchers created the pills to release the drugs and then break up into smaller parts that can be passed through the digestive system.
The researchers worked with the Institute for Disease Modeling in Bellevue, Washington on this project. Their goal was to predict how much impact the weekly drug could have on protecting people against HIV. The researchers determined that when patients go from a daily dose to a weekly dose, it could improve the rate of HIV preventative treatment by 20 percent. The figure was put into a computer model of HIV transmission in South Africa and shows that as many as 200,000 to 800,000 new cases of HIV could be prevented over the next 20 years with this new technology.
According to Anthony Fauci, director of the National Institute of Allergy and Infectious Disease, a longer acting and less invasive form of oral treatment could be an important part of the future when it comes to the treatment of the AIDS/HIV pandemic. Fauci stated that substantial progress has been made to improve antiretroviral therapies and enable a person with HIV to live a nearly normal lifespan and reduce the risk of becoming infected.
However, he stated that lack of adherence to daily therapies of infected people and pre-exposure prophylaxis for uninfected but at-risk people is still a problem. New approaches and tools for HIV prevention and treatment, in addition to a wider implementation of existing approaches, are still important in ending the HIV pandemic. He stated that new technology, such as the delayed-release tablet, helps us get one step closer to achieving this goal.
The research team that worked on this project is now trying to adapt the technology to other diseases that could benefit from drug adherence and weekly drugs. The team stated that because the capsules are designed to hold different drugs in each arm, it’s easy to swap out the drugs to treat another disease.
According to Kirtaine, putting other drugs into the system is easier because the core system does not change. All the researchers have to do is change the rate in which the drugs are released. It can either be slowed down or sped up, depending on the patient’s needs. The research team is also working on pills that can stay in the body for longer.
Other long-acting drug delivery systems are currently being investigated, including oral and injectable nanoparticles and vaginal rings. Many of these studies are at the most advanced stages of clinical testing. Treatment of injectable nanoparticles and vaginal rings have resulted in sustained local and systemic concentrations while orally administered drugs have led to enhanced bioavailability of drugs and reduction in doses.
Computer modeling has confirmed that patients experience an improvement in adherence within weekly dosing, which has the potential to prevent hundreds of thousands of new HIV cases. Researchers expect this technology to impact large populations and make it easier for more people to take the drug if they only need to remember to take it once per week.
Limitations with the study include using a swine model for studying the gastric residence and release of the drugs. However, the researchers noted that the anatomy of a pig stomach closely resembles a human’s stomach. Additionally, the pigs used in this study had a body weight that was similar to a humans and gastrointestinal time in pigs is usually slower than in humans. The gastric emptying rate of the pigs can also vary depending on the size and age of the animal, as well as whether the pig has been fed or fasted.
The project was funded by the Division of Gastroenterology at Brigham and Women's Hospital, the Bill and Melinda Gates Foundation, the National Institutes of Health, and the Bill and Melinda Gates through the Global Good Fund.