Boston, MA -- Daily oral contraceptive pills allow women to manage their fertility, but this method of contraception relies on a user remembering to take her pill at the same time every day. In a multi-national survey, up to half of women taking an oral contraceptive reported missing at least one dose over a three-month period. Among women using oral contraceptive pills, the chance of pregnancy is about 9 percent every year. A team led by investigators from Brigham and Women's Hospital and MIT is designing a new method to help improve adherence and reduce the risk of pregnancy by offering an oral contraceptive that could be taken once a month. Building on previous research to develop slow-release pills that can reside in the stomach for days or weeks, the team reports in Science Translational Medicine that, for the first time, it has achieved month-long delivery in preclinical models.
"Our capsule represents a major advancement toward providing women with a once-a-month contraceptive. For many, this may be hard to believe. But our preclinical data is encouraging us along that road," said co-corresponding author Giovanni Traverso, MD, PhD, a gastroenterologist and physician-researcher at the Brigham and MIT. "We began our work on extended drug release by working with treatments for malaria, tuberculosis and HIV. But early on, we were having conversations about the potential impact that extended drug release could have for family planning. We wanted to help empower women with respect to fertility control and are pleased to report our progress toward that goal."
The team designed a drug-delivery vehicle that consists of six arms joined by an elastic-coated core. The arms were loaded with the oral contraceptive drug levonorgestrel and folded up into a capsule that can be swallowed. Once in the stomach, the arms unfold and have a span that is larger than the opening of the human pylorus, helping the system stay in the stomach where it can release the drug over time.
The research team tested the concentration of oral contraceptive over time in a pig model and measured the presence of the drug in the bloodstream for animals who had been given the extended-release form versus an immediate release tablet. For the tablet, dosage tapered off after six hours. For the extended-release form, the team observed concentrations of the drug for up to 29 days.
Work is now underway to bring the extended-release pill closer to human trials. Next steps will include scaling up manufacturing processes and safety evaluations.
Co-authors of this work include Ameya R. Kirtane, Tiffany Hua, Alison Hayward, Ambika Bajpayee, Aniket Wahane, Aaron Lopes, Taylor Bensel, Lihong Ma, Frank Z. Stanczyk, Sierra Brooks, Declan Gwynne, Jacob Wainer, Joy Collins, Siid Tamang, and Robert Langer.
This work was funded by the Bill and Melinda Gates foundation Grant No. OPP1139927. Traverso, Langer and Kirtane are co-inventors on patents describing the use of gastric retentive drug delivery systems. Traverso and Langer have a financial interest in Lyndra Therapeutics, a biotechnology company focused on the development of oral drug delivery for long drug release. Hayward is a consultant for Lyndra Therapeutics.
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Science Translational Medicine