This week I am going to focus on the contraceptive implant. As mentioned in the first blog post, the birth control implant is a flexible rod, composed of non-biodegradable ethylene vinylacetate co-polymer, that continually releases the hormone etonogestrel. Nexaplanon is currently the only FDA approved birth control implant, and it must be removed after three years.
While it is fairly easy to insert the rod, as it is packaged with an applicator that allows a trained medical professional to smoothly insert it into one’s upper arm, removal requires a slightly more complicated medical procedure. A scalpel is used to make an incision and cut the implant out, a procedure that can be frightening for some women. Furthermore, as with any procedure, there is a risk of infection.
Contraceptive implants have been rising in popularity in less developed countries where there is a need for family planning solutions. However, for women who have limited access to medical care, it can be challenging for women to find a trained professional who is able to remove the implant after 3 years.
For these reasons, there have been recent initiatives to develop biodegradable contraceptive implants, which would eliminate the need for the implant to be removed after three years! In addition, the implant would not start to degrade until one year after implant, allowing a woman to have the implant surgically removed if she experiences adverse side effects. This research, sponsored by the Gates Foundation and USAID, is actually being done here at Yale in the Saltzman Lab – how cool!
Composition
The biodegradable contraceptive currently being developed is made of a non-toxic polymer called poly(ω-pentadecalactone-co-p-dioxanone) [poly(PDL-co-DO)]. That’s a mouthful, but here’s a picture of its chemical structure:
Basically, a polymer is a large molecule that is composed of many small, repeating molecules that are bound together by covalent bonds. Covalent bonds result from the sharing of electrons between atoms that are directly adjacent to one another. Polymers also have secondary bonds, such as hydrogen bonds, which gives polymers properties such as elasticity and mobility – that’s a vital characteristic for contraceptive implants.
Biodegradability
A biodegradable material is a material that is able to decompose (i.e. the covalent bonds are cleaved) into molecules that are naturally found in the body, rendering the products to be non-toxic to the body. Degradation can occur through surface erosion (degradation from the edges moving inward) or through bulk degradation (slow degradation of materials throughout). When the material is fully degraded, the products are processed by the body’s metabolism.
In the case of the contraceptive implant, this would mean that the device would completely disappear after a given period of time, making it seem as if it had never been implanted. This biodegradable component may be a solution to the issues associated with non-biodegradable implants and the need for them to be removed. Nevertheless, in order to allow women to remove the device if they are experiencing adverse side effects, the bonds in the polymers must be able to stay intact for an initial period of time.
Slow release of etonogestrel
As mentioned above, etonogestrel is slowly and continuously released from the implant. So how would this work? Nanoparticles.
Nanoparticles are solid, submicron-sized particles that can be used as a therapeutic agent. A nanoparticle consists of a bulk material (e.g. a polymer) that encapsulates and carries an active substance, such as a drug, to a target location. As the polymer degrades, the drug (e.g. etonogestrel) is released into the bloodstream over a period of time, allowing for controlled delivery of drugs. This is especially important in the case of LLRCs, as the goal is to have continuous release of low amounts of etonogestrel in order to prevent pregnancy over an extended period of time. If all of the etonogestrel were released at once, that would not be good.
Stress and Strain
One final consideration is the fact that the implant is injected into the muscle tissue in the inner arm, subjecting it to tensile and compressive forces as the arm moves around. The implant must have properties that prevent it from breaking or snapping when subjected to these forces. As such, its elastic modulus must be fairly low, because it must be able to stretch and condense as a result of tensile and compresses forces without deforming (i.e. without permanently changing the molecular structure). Nevertheless, the elastic modulus cannot be too low, as it needs to be firm enough so as it doesn’t dislodge from the position in the muscle it is placed.
So, is this feasible?
Overall, a biodegradable contraceptive implant would provide an excellent solution to the issues related to the removable of non-biodegradable contraceptive implants. These issues include, but are not limited to, pain and discomfort associated with the procedure, the risk of infection, and the inability to have access to a trained professional to remove the device.
Nevertheless, I think one of the largest considerations may be efficacy of the device. Hormonal birth control relies on the continuhttps://www.nexplanon.com/nexplanon-removal/ous release of hormones, but I wonder how the degradation process may affect this release. If the implant starts degraded after year 1 and is completely degraded by year 3, do the levels of etonogestrel change at all as year 3 approaches? And at one point would women have to begin using alternative forms of birth control? These are questions to ask going forward and something that I’m sure is being considered in the development of biodegradable implants.
