Researchers at the Massachusetts Institute of Technology (MIT) have developed a new drug delivery system that could make long-lasting contraception as simple as one clinic visit, one thin needle, and one moment of decision.
The study, published in March 2025 in the journal Nature Chemical Engineering and funded by the Bill and Melinda Gates Foundation, describes a method where drug crystals are injected beneath the skin through a narrow needle and then self-assemble into a lasting depot that releases hormones steadily over months or even years.
Pre-clinical results are already strong, human trials are in preparation, and the technology has been specifically designed to work in the places where it is needed most.
For the estimated 218 million women in low and middle-income countries who want to avoid pregnancy but currently have no reliable access to modern contraception, according to research from the Guttmacher Institute, this innovation could be genuinely transformative.
The name given to the system by its creators says a great deal about what makes it different.
They call it SLIM, which stands for Self-aggregating Long-acting Injectable Microcrystals.
That name captures the essential mechanic: tiny crystals that, once injected, organize themselves into a compact structure inside the body, doing the work that surgical implants previously required a trained clinician and a small incision to achieve.
The research team was led by Giovanni Traverso, an associate professor of mechanical engineering at MIT and a gastroenterologist at Brigham and Women’s Hospital.
The lead authors of the study were Vivian Feig, formerly of MIT and now an assistant professor of mechanical engineering at Stanford University, Sanghyun Park, an MIT graduate student, and Pier Rivano, a former visiting research scholar in Traverso’s lab.
Their work was published in MIT News on March 24, 2025, and the full study can be found in Nature Chemical Engineering, volume 2, pages 209 to 219, under the citation: Feig VR, Park S, Rivano PG, et al. Self-aggregating long-acting injectable microcrystals. Nature Chemical Engineering. 2025;2:209-219.
How the Study Was Conducted
The research team set out to solve a problem that has challenged pharmaceutical scientists for decades.
How do you deliver a drug that needs to stay active inside the body for months or years, without requiring surgery to implant it and without forcing a patient back to a clinic every few months for a repeat injection?
Existing options each come with real drawbacks.
The Depo-Provera injection, one of the most widely used hormonal contraceptives in the world, lasts roughly three months.
That means a woman needs four clinic visits every year to stay protected, which in remote or under-resourced communities is frequently not possible.
Long-acting implants like Nexplanon solve the duration problem by lasting up to three years, but they require a trained provider to make a small incision in the arm, insert a flexible rod beneath the skin, and later retrieve it surgically when the effect wears off or the woman wishes to stop.
That level of procedural complexity limits where and by whom they can be offered.
The MIT team wanted something in between: the staying power of an implant with the simplicity of an injection.
They focused their work on levonorgestrel, a synthetic hormone that has been used in contraceptives for decades and is found in many currently available pills, implants, and intrauterine devices.
One important physical property of levonorgestrel is that it is hydrophobic, meaning it repels water, and it forms crystals naturally.
The key discovery came when the researchers suspended those levonorgestrel crystals in a specific organic solvent called benzyl benzoate.
Benzyl benzoate is not a new compound.
It has been used as an additive in injectable pharmaceutical formulations for many years and carries a known safety profile.
What makes it remarkable in this context is a simple physical property: it does not mix with biological fluids.
When the researchers injected the crystal-and-solvent mixture into tissue, the body’s water-based environment immediately forced the solvent and the crystals apart.
With the solvent unable to integrate into surrounding fluids, the drug crystals had nowhere to go but toward each other.
They packed together tightly, forming what the researchers describe as a monolithic implant, a dense, organized depot just beneath the surface of the skin, with no surgery, no suture, no polymer scaffold, and no incision required.
As Traverso described it in the MIT News release: “The solvent is critical because it allows you to inject the fluid through a small needle, but once in place, the crystals self-assemble into a drug depot.”
Once the depot forms, it behaves like a slow-release reservoir.
The hormone erodes from the surface of the depot gradually and enters the surrounding tissue, from which it is absorbed into the bloodstream at steady, controlled levels.
The researchers also discovered they could adjust how quickly the depot releases the drug by changing its density.
A more tightly packed crystal structure releases the hormone more slowly, extending the effective period.
A less dense structure releases it more quickly.
This tunability gives the system flexibility to be formulated for different durations of coverage depending on a woman’s needs, from six months to potentially two years from a single injection.
To further refine control over release rates, the team added a very small quantity of a biodegradable polymer, less than 1.6 percent by weight, which is far below the concentrations used in earlier long-acting injectable formulations.
That small addition helped moderate the release speed without making the suspension too thick to push through a fine needle.
The entire injection can be administered through a 30-gauge needle, the same gauge commonly used for blood draws and insulin injections.
That detail matters more than it might initially seem.
Traverso addressed it directly, saying: “Needle size and liquid viscosity are crucial considerations for commercial translation of injectables. Our engineering challenge was finding a way to maximize comfort for patients by using smaller needles, which cause less bruising or bleeding, and to make the viscosity low enough for easy application with the syringe by hand.”
Older long-acting injectable formulations that attempted similar goals required thicker polymer concentrations, which made the liquid viscous and difficult to push through a narrow needle, forcing the use of larger, more painful gauges.
The SLIM system bypasses that problem entirely because the suspension is fluid before injection, and the self-assembly only occurs after it enters the body.
Findings From the Study
The pre-clinical results confirmed what the theory predicted.
After injection, the crystal depot formed reliably and held its structure over extended observation periods.
In animal studies, more than 85 percent of the medication remained in the depot system after three months, indicating that the reservoir does not dissolve rapidly or disperse unevenly into surrounding tissue.
The hormone release was measured as controlled and sustained, meaning levels in the bloodstream remained within a therapeutically effective range rather than spiking immediately after injection and then dropping off quickly, which is the pattern that makes shorter-acting formulations less reliable over time.
The depot’s structure gave it longevity.
Because the crystals pack into a compact, low-surface-area mass, the body can only access the drug from the outer edges of the depot at any given time.
As that surface erodes and the depot slowly shrinks, the interior continues to hold the bulk of the remaining drug, releasing it progressively.
The researchers also confirmed that the depot can be physically located and removed if a woman changes her mind about contraception or experiences side effects.
That characteristic is medically and ethically significant.
A woman who receives the injection retains the option to discontinue it before the full duration has elapsed, which addresses one of the most legitimate concerns raised about long-acting contraceptives historically.
Beyond contraception, the study highlighted that the same delivery platform could be loaded with other drugs entirely.
The researchers specifically identified potential applications in HIV prevention and treatment, tuberculosis, neuropsychiatric conditions, and other chronic diseases that currently require frequent medication.
The underlying mechanism, which depends on the physical properties of the solvent and the crystal-forming nature of the drug rather than the specific chemistry of levonorgestrel, means that other hydrophobic, crystal-forming compounds could potentially be delivered the same way.
That makes SLIM not just a contraceptive innovation but a potentially versatile drug delivery platform with broad implications for global health.
What Most People Get Wrong About Long-Acting Contraception
There is a widely held assumption that longer-lasting birth control must be more complex to deliver.
The intuition makes sense on the surface: if something stays active for two years, surely it requires more infrastructure, more training, more equipment than something that lasts three months.
The SLIM injection turns that assumption on its head.
Because it flows through a thin, standard needle and requires no surgeon, no incision, and no specialized instrument for placement or retrieval, it can potentially be administered by a trained community health worker at an outreach event in a village without a permanent clinic.
It does not require refrigeration of complex biological compounds.
It does not require a follow-up appointment to remove an implant.
The very thing that makes it durable is also, by design, what makes it simple.
The crystals do the work of forming a lasting structure entirely on their own, inside the body, the moment the injection is complete.
There is also a persistent myth worth addressing about long-acting contraceptives and women’s autonomy.
The history of long-acting birth control carries real ethical weight.
There are documented cases from earlier decades in which implants and injections were administered to women in lower-income countries without adequate informed consent, in programs shaped more by population targets than by individual reproductive choice.
Those failures were real, and the concern they raised is legitimate.
But they were failures of policy and practice, not inherent properties of the technology.
The SLIM research team and the Gates Foundation have both explicitly identified informed consent, user education, and community engagement as non-negotiable pillars of any deployment strategy.
The ability to remove the depot if a woman wishes to stop is also built into the design from the beginning, not added as an afterthought.
Lead author Vivian Feig stated: “The overarching goal is to give women access to a lot of different formats for contraception that are easy to administer, compatible with being used in the developing world, and have a range of different timeframes of durations of action.”
The emphasis on options, flexibility, and choice is woven into the scientific rationale itself.
A woman who wants six months of coverage can have that.
A woman who wants two years can have that.
A woman who wants to stop after four months can have that too.
How This Research Applies to Real Life
The global picture of unmet need for contraception is not an abstraction.
According to data from the Guttmacher Institute, out of 923 million women of reproductive age in low and middle-income countries who want to avoid pregnancy, 218 million are doing so without any modern method.
They want protection. They do not have it.
Meeting that unmet need, according to the same research, would reduce unintended pregnancies, unsafe abortions, and maternal deaths by roughly two-thirds.
The United Nations Population Fund reported that in 2024 alone, contraceptives they supplied prevented 18 million unintended pregnancies, averted 7.5 million unsafe abortions, and prevented 39,000 maternal deaths.
That is the impact of increased access to methods that already exist.
The scale of what a long-lasting, easy-to-administer option could contribute is considerably larger.
Consider what a two-year injection means for a woman in a rural community in sub-Saharan Africa or South Asia, where the nearest clinic might require several hours of travel on poor roads, where the cost of transportation alone can make quarterly injections financially impossible, and where taking time away from family or work responsibilities for repeated medical visits is not always feasible.
A single clinic visit or outreach appointment that provides two years of reliable protection eliminates every one of those barriers in one step.
It removes the transportation cost, the time burden, and the risk of a missed appointment leading to an unintended pregnancy.
It removes the need for discretion around monthly pharmacy visits in communities where seeking contraception can carry social stigma.
The argument for this technology is not that it is better than other methods for every woman in every context.
It is that it fills a specific and enormous gap: reliable, long-term protection for women for whom every existing method requires more access, more consistency, or more resources than they can reliably maintain.
There is a parallel argument for higher-income settings as well.
In the United States, research published in 2024 in the journal Contraception noted that the unintended pregnancy rate remains close to 45 percent.
The most common reason modern contraceptives fail is not that they stop working.
It is that they are not used correctly and consistently over time.
Daily pills are missed.
Quarterly injection appointments are delayed.
Ring insertions are timed incorrectly.
A method that requires a single decision and delivers two years of protection removes the consistency requirement entirely.
It is difficult to misuse a method you only need once every two years.
The Science of Self-Assembly in Plain Language
It helps to understand why this method works by thinking about what normally limits long-acting injectable drugs.
Most medications injected into the body either dissolve into the bloodstream quickly or, in formulations that attempt longer duration, require thick concentrations of polymers to slow that absorption.
Those thick polymer formulations are uncomfortable to inject, require larger needles, and have practical limitations on how long they can sustain release before their structure degrades.
The SLIM approach works differently because it does not rely on a heavy polymer framework at all.
Instead, it exploits a basic physical principle.
Benzyl benzoate and body fluids are immiscible, meaning they naturally refuse to mix, the way oil and water remain separate regardless of how much you shake them.
When the crystal suspension is injected into subcutaneous tissue, the water-based biological environment surrounding the injection site immediately exerts pressure on the solvent.
The solvent, unable to integrate, essentially retreats.
As it does, the drug crystals, which were floating freely inside it, suddenly find themselves in a water-dominated environment they are designed to repel.
Their only stable configuration is to pack together.
And so they do.
Within seconds of injection, the crystals self-organize into a dense, compact mass, forming a monolithic depot without any scaffolding, framework, or manual arrangement.
The resulting structure has far less exposed surface area than the freely dispersed crystals would have had.
Less surface area means slower contact between the depot and the surrounding tissue.
Slower contact means slower erosion.
Slower erosion means slower release of the hormone into the bloodstream.
The depot, in other words, does not simply sit there unchanged.
It is slowly consumed from the outside in, releasing the hormone as each outer layer erodes, while the interior continues to hold the reserve.
By adjusting how densely the crystals pack, and by adding that small trace of biodegradable polymer, the researchers can shift the erosion rate and therefore the duration of effectiveness.
This is what gives SLIM its flexibility.
It is not one fixed formulation.
It is a platform with adjustable parameters, capable of being tuned for different timelines and eventually loaded with different drugs for different conditions.
The Gates Foundation’s Long-Term Strategy
The Bill and Melinda Gates Foundation’s involvement in this project is deliberate and consistent with a long-standing commitment.
Expanding access to contraception in low and middle-income countries has been a central pillar of the Foundation’s global health work for over two decades.
A senior program officer at the Foundation, Kirsten Vogelsong, wrote in a 2023 article on the Gates Foundation website that investing in sexual and reproductive health in low and middle-income countries would avert 76 million unintended pregnancies and 186,000 maternal deaths.
The Foundation previously funded the development of the DARE-LARC1, a chip-based implantable contraceptive device that received approximately $48.95 million in Gates Foundation funding through Daré Bioscience in 2021.
The SLIM injection represents a different and in many ways simpler approach, one that requires no electronic components, no remote control system, no specialized retrieval equipment, and no infrastructure beyond a standard syringe.
If clinical trials go well, it can move through existing vaccine and injectable medication distribution networks already operating in low-income countries, through organizations like GAVI, USAID, and UNFPA, without requiring new cold chains, new training programs for surgeons, or new facility investments.
That compatibility with existing infrastructure is one of the most underappreciated qualities of this innovation.
A breakthrough that requires an entirely new delivery ecosystem to function is a breakthrough that takes decades to reach the people who need it most.
A breakthrough that slots into what already exists can scale far faster.
What Happens Next
The MIT team is currently conducting further pre-clinical studies in preparation for human trials.
That work is focused on confirming long-term safety, refining the formulation for different durations, and building the evidence base required to begin testing in humans with regulatory oversight.
Human clinical trials are expected to begin within the next year, with international trials to follow, with particular emphasis on low and middle-income countries where the technology could have its greatest public health impact.
The researchers are also exploring multi-drug depots, a single injection containing more than one active compound.
The most discussed possibility is a formulation that combines contraception and HIV prevention in a single shot.
In regions where both unintended pregnancy and HIV transmission are significant public health concerns, and where clinic visits are infrequent and logistically difficult, a combined injection would address two critical needs at once.
That application remains further from clinical use than the contraceptive-only formulation, but the underlying platform already supports it in principle.
The same self-assembly mechanism that works for levonorgestrel can potentially work for antiretroviral compounds, provided those compounds share the relevant physical properties.
The regulatory timeline, assuming successful human trials, would likely make the technology available in global health markets before the end of the decade.
Initial projections suggest the formulation could be affordably manufactured and distributed at scale, which is critical for adoption in the low-income country context where the need is greatest.
A Small Needle. A Large Idea.
There is something quietly remarkable about the fact that years of effective, reversible birth control could eventually fit inside a standard syringe.
Just a single injection, self-assembling beneath the skin into something that works reliably for up to two years and then, when the time is right, is gone.
For millions of women who currently navigate a complicated, expensive, and often inaccessible landscape of contraceptive options, that simplicity is not merely convenient.
It is the difference between having real control over one’s reproductive future and not having it at all.
The science is still moving through the pre-clinical stage, and there are meaningful steps remaining before this becomes a globally available option.
But the research is rigorous, the funding is committed, the need it addresses is among the most consequential in global public health, and the technology is built from the ground up to reach the people most likely to benefit from it.
That combination of scientific credibility, practical design, and genuine urgency is rare.
It is worth following closely.
Sources
MIT News: Engineers develop a better way to deliver long-lasting drugs, March 2025
Guttmacher Institute: Investing in Sexual and Reproductive Health in Low and Middle-Income Countries
Gates Foundation: Why We Must Invest in New Women’s Contraceptive Options, 2023
