One shot of tiny crystals has a contraceptive effect for up to 2 years

Engineers at the Massachusetts Institute of Technology have developed a new way to deliver certain drugs in larger doses and with less pain by administering them as a suspension of tiny crystals. Once under the skin, the crystals collect into a drug “depot” that can be stored for months or years, eliminating the need for frequent injections.

This approach may be useful for delivering long-acting contraceptives or other drugs that need to be taken over a long period of time. Because the drugs are dispersed in suspension before injection, they can be administered through a tiny needle, which is easier for patients to tolerate.

“We have shown that we can provide very controlled, sustained delivery through a small needle capable of acting for months or even years.”

Giovanni Traverso, associate professor of mechanical engineering at MIT, a gastroenterologist at Brigham and Women’s Hospital (BWH), an associate member of the Broad Institute and senior author of the study

The project was initiated as part of a program funded by the Gates Foundation to increase contraceptive options, especially in developing countries.

“The main goal is to give women access to many different contraceptive formats that are easy to use, that are compatible with use in developing countries, and that have different expiration dates,” say the researchers. – “In our particular project, we were interested in trying to combine the benefits of long-acting implants with the ease of self-administration of injectables.

Injectable suspensions are sold in the US and other countries, but these drugs disperse into the tissues after injection, so they are only effective for three months. Other injectable drugs have been developed that can form longer-lasting depots under the skin, but these usually require the addition of precipitating polymers, which can range from 23 to 98 percent of the solution by weight, which can make the drug difficult to administer.

Experts at the Massachusetts Institute of Technology wanted to create a drug that could be injected through a small-gauge needle and that would work for at least six months and no more than two years. They began working with a birth control drug called levonorgestrel, a hydrophobic molecule that can form crystals. The team discovered that if these crystals are suspended in a certain organic solvent, they clump together into a very compact implant after injection. Since such a depot did not require a large amount of polymer to form, the drug could be easily injected through a narrow needle.

The solvent, benzyl benzoate, is biocompatible and has previously been used as an additive to injectable drugs. The team found that the solvent’s weak ability to mix with biological fluids allows the solid drug crystals to self-assemble into a depot under the skin after injection.

“The solvent is very important because it allows the liquid to be injected through a small needle, and once injected, the crystals self-form a drug depot,” Traverso says.

By changing the density of the depot, researchers can regulate the rate at which drug molecules are released in the body. In this study, the researchers showed that they can change the density by adding a small amount of a polymer such as polycaprolactone, a biodegradable polyester.

This demonstrates the customizability of the system, which can be designed to meet a wider range of contraceptive needs as well as customized dosing regimens for other therapeutic applications.

The researchers tested their approach by injecting a drug solution subcutaneously into rats and showed that the drug depot could remain stable and gradually release the drug over three months. After the end of the three-month study, about 85 percent of the drug remained in the depots, suggesting that they can continue to release the drug over a much longer period of time.

Once the depot is formed, the drugs are compact enough that they can be surgically removed if treatment needs to be stopped before the drug is fully released.