Longer-acting method that is injectable probed

Contraceptive injectables are a popular form of birth control for women around the world, with more than 35 million women relying on the method. The contraceptive shot is a popular form of family planning in the United States, particularly among teens. About 20% of females ages 15-19 in 2002 and 2006-2010 reported contraceptive injectable use in the United States.1

Contraceptive injections, given every one to three months, represent an effective form of birth control that does not require daily compliance and can be used discreetly. Despite their popularity, many users might discontinue use early due to missed reinjection appointments.2

With funding from the Bill & Melinda Gates Foundation of Seattle, FHI 360, a global nonprofit human development organization based in Durham, NC, has launched a project to support early testing of innovative approaches to developing an injectable contraceptive that would last for six months. As part of this project, FHI 360 in 2012 issued a Request for Proposals for proof-of-concept testing of candidates that have the potential to be developed into a longer-acting injectable. Concepts were received from lead drug delivery research groups in the United States, Europe, India, and China, and they represented a wide range of innovative approaches. After a rigorous review by internal and external experts, three proposals were selected to move forward with proof-of-concept testing.

As the next step, FHI 360 will work with its new partners to evaluate these three promising technologies, states Vera Halpern, MD, FHI 360's director of the development of a longer-acting injectable contraceptive project. "For the products that successfully complete proof-of-concept testing, we will move as rapidly as possible to begin human clinical trials and complete the studies necessary to obtain regulatory approvals for broader product use," says Halpern. "The development of a longer-acting injectable would improve continuation rates for women around the world, resulting in fewer unwanted pregnancies."

Different tactics eyed

Three proposals were selected to move forward for proof-of-concept testing:

  • poly(lactic) and poly(lactic-co-glycolic) (PLA/PGLA) microspheres releasing levonorgestrel, in research by Shanghai (China) Institute of Planned Parenthood Research;
  • nanostructured porous silicon microparticles releasing a contraceptive steroid, under study by the University of California, San Diego in La Jolla;
  • biodegradable polymeric gel formulation releasing levonorgestrel, in formulation at the University of Tennessee Health Science Center in Memphis.

At the University of California, San Diego, the major challenge is to engineer the nanomaterial to deliver drug at a constant rate for the duration of the therapy, and then disappear very quickly when the drug reservoir is exhausted, explains Michael Sailor, professor and Leslie E. Orgel Scholar in Inorganic Chemistry in the Department of Chemistry and Biochemistry. The scientific team is designing the system such that the contraceptive drug will be delivered at a therapeutic concentration for up to six months, then quickly taper to allow the individual to rapidly regain fertility, Sailor states.

At the University of Tennessee Health Science Center in Memphis, scientists are looking at a biodegradable polymeric gel formulation, constituted from biodegradable polyesters, the active pharmaceutical ingredient levonorgestrel, and a vehicle for injection, explains Tao Lowe, PhD, associate professor of pharmaceutical sciences & biomedical engineering at the university. After injection, the formulation forms a solid implant at the injection site within a short time. The active pharmaceutical ingredient, levonorgestrel, is slowly released out from the in-situ formed implant into the surrounding body fluid, where it eventually enters the bloodstream, states Lowe. By designing the dosage forms, the release of the drug will be adjusted to the desired six months, and the polyesters in the dosage form will gradually degrade on site after injection, she states.

Due to the complete degradation of material, no polymers will accumulate in in the body, and no surgical removal will be required, states Lowe. After discontinuation, the return to fertility will be fairly rapid and predictable, scientists believe.

Research is first step

Injectables currently used around the world are effective for 1 to 3 months, depending on the formulation, which requires women to return to their provider 4 to 12 times per year. Missed follow-up appointments are an important reason for discontinuation. A longer-acting injectable would likely increase compliance, improve continuation rates, and increase typical-use contraceptive effectiveness, and thus help reduce rates of unintended pregnancies, say FHI 360 officials.

"This project is the first step toward bringing a game-changing injectable contraceptive to market that provides six months of protection, thereby expanding contraceptive access and choice for women around the world," says Halpern.

References

  1. Martinez G, Copen CE, Abma JC. Teenagers in the United States: Sexual activity, contraceptive use, and childbearing, 2006-2010 National Survey of Family Growth. National Center for Health Statistics. Vital Health Stat 23(31). 2011.
  2. Polaneczky M, Liblanc M. Long-term depot medroxyprogesterone acetate (Depo-Provera) use in inner-city adolescents. J Adolesc Health 1998; 23(2):81-88.