Novel microneedle technology may offer alternative to surgically implanted contraceptives

Key takeaways:

• A novel technology would allow for nonsurgical injection of the long-acting contraceptive levonorgestrel.
• If successful in humans, the technology could be used for delivery of other long-acting therapeutics.

A long-acting contraceptive implant delivered with novel microneedle technology could provide a more accessible, nonsurgical option for women and increase the likelihood of medication use, according to preclinical data.

Researchers have struggled to develop long-acting injectable drugs that combine a long duration of action — at least 3 months — with the capacity for self-administration through small-gauge needles, according to Giovanni Traverso, MD, BChir, PhD, associate professor in the department of mechanical engineering at MIT, associate physician in the division of gastroenterology at Harvard Medical School and an associate member of the Broad Institute of MIT and Harvard. This is because any such combination relies on polymer excipients to sustain long-term drug release and secure mechanical integrity, which can increase solution viscosity, Traverso and colleagues wrote in Nature Chemical Engineering.

“One of the things we see with contraception — but also with tuberculosis, HIV and neuropsychiatric conditions — is that there are some interventions or therapeutics that can provide a steady level of drug, but they require larger needles,” Traverso told Healio. “The challenge is people do not like injections. Is there a way to engineer something to help overcome those types of challenges? That is our focus.”

Traverso and colleagues developed self-aggregating long-acting injectable microcrystals (SLIM) for levonorgestrel in an injectable formulation as a proof-of-concept demonstration to show the potential of the technology, according to the researchers. Once injected, the drug microcrystals self-aggregate in the subcutaneous space to form a monolithic implant with a low ratio of polymer excipient to drug, Traverso said.

In a press release, the researchers described the technology as “like tiny puzzle pieces that, once injected inside the body, undergo solvent exchange to assemble into a single solid implant that slowly releases the drug as the surface erodes.”

“There are drugs, like levonorgestrel used here, that have some unique properties in that they are hydrophobic,” Traverso told Healio. “What we were able to figure out is by using a solvent or fluid that can help solubilize the drug, we could load that solution in a way that, when injected, that solvent would go away and leave behind that solid depot of drug. Because it is fluid and we are loading it, it is much easier to inject. That was critical. We also wanted that object to be solid enough that we could retrieve it if we needed to. Making the needle smaller is enabling and facilitating self-administration.”

The solvent-exchange-mediated aggregation mechanism allows injections through needles as small as 30 G with no polymer and 25 G with a small amount of polymer while extending the drug release time frame. In vivo studies demonstrated that the compacted microcrystal structure reduces average drug release rate.

Histological analysis confirmed the components were well tolerated, supporting safety for potentially broad clinical applications beyond contraceptives, Traverso said.

“Specifically, in applications such as contraception, SLIM’s capability for prolonged drug release could significantly reduce the frequency of administration compared with current self-administrable options such as Depo-Provera and Sayana Press, potentially transforming the landscape of contraceptive technology,” the researchers wrote.

Traverso said the researchers are still actively working on the platform and applying it to several other infectious and neuropsychiatric conditions.

“Our goal is to work toward further translation toward humans,” Traverso said. “From a manufacturing standpoint, this [design] is simple and low cost. This work was funded by the Gates Foundation, an organization that considers those aspects from an early stage. We see this work as highly translatable. We hope to be in humans [with this technology] within the next 3 to 5 years, assuming further funding. I am optimistic. This is a team effort among people from different fields and institutions. When you bring those different fields together, you create situations where you can generate solutions.”

For more information:

Giovanni Traverso, MD, BChir, PhD, can be reached at cgt20@mit.edu; X: @cgtraverso; Bluesky: @cgt20.bsky.social.