A new long-acting contraceptive designed for self-management of women can provide a new family planning opportunity, especially in developing countries where access to health care may be limited, suggests a recent study. Preventive agents will be delivered using micronedle skin patch technology originally developed for painless administration of vaccines.
Long-acting contraceptives now available provide the highest level of efficacy, but usually require a healthcare professional to inject a drug or implant a device. Short-acting techniques, on the other hand, require frequent user compliance and are therefore often not as effective. In animal experiments, an experimental micronedle contraceptive drug delivered a therapeutic level of contraceptive hormone for more than a month with a single application to the skin.
When the patch is applied for several seconds, they discontinue microscopic needles and remain below the surface of the skin, where biodegradable polymers slowly release the contraceptive drug levonorgestrel over time. Originally designed for use in areas of the world with limited healthcare access, the microneedle contraceptive might potentially provide a new family planning alternative to a wider population.
The research was reported January 1
] "There is great interest in offering more opportunities for long-acting contraceptives," says Mark Prausnitz, a regent's professor of the School of Chemical and Biomolecular Engineering at the Georgia Institute of Technology and the paper's author. "Our goal is that women should be able to self-administer long-acting contraceptives with the micro-patch, which will be applied to the skin for five seconds only once a month."
Long-acting contraceptives are now available in formats such as patches to be worn continuously, intrauterine devices (IUDs) to be placed by trained healthcare professionals and drugs injected with hypodermic needles. Ultimately, if the micronedle contraceptive patches are approved for use, it may become the first self-administered, long-acting contraceptive that does not involve a conventional needle injection. Like other long-acting contraceptive methods, the micronedle contraceptive patches will interfere with menstrual cycles in women using it.
As the small needles remain in the skin for the release of the hormone, scientists led by the Georgia Tech postdoctoral researcher Wei Li developed a mechanical technique that would allow the drug-containing microparticles to detach from the patch's support material. To achieve this, researchers molded small air bubbles into the top of the microparticles, creating a structural weakness. The resulting microparticles are strong enough to be pressed into the skin, but when the patches are then changed to one side, the shear force breaks the small structures in the skin. The plastic backing can then be discarded.
Experimental spots designed to deliver a sufficient amount of the hormone to humans have been developed, but not yet tested, noted Prausnitz, who owns J. Erskine Love, Jr. Chair in Chemical and Biomolecular Engineering at Georgia Tech. Researchers also investigate whether a single patch could carry enough hormone to provide contraception for as long as six months.
"The micronedle patch delivery platform developed by Dr. Prausnitz and his contraceptive colleagues is an exciting advance in women's health," says Gregory S. Kopf, director of R&D Prevention Technology Innovation at FHI 360. "This self-managed Long-acting contraceptives will give women discreet and comfortable control over their fertility, leading to a positive impact on public health by reducing both unwanted and unwanted pregnancies. "
The microparticles are molded from a mixture of biodegradable polymers, poly (milk-co- glycolic acid) and poly (lactic acid) commonly used in resorbable sutures, said Steven Schwendeman, Ara Paul Professor and chair of the Department of Pharmaceutical Sciences at the University of Michigan and a collaborator on this project. Mel and glycolic acid are present naturally in the body, which contributes to the biocompatibility of the polymer material, he said.
"We choose polymeric materials to meet specific design goals such as micronutrient strength, biocompatibility, biodegradation and release time and formulation stability," Schwendeman explained. "Our team then treats the polymer into microparticles by dissolving the polymer and drug in an organic solvent, shaping the mold and then drying the solvent to create the microparticles. The polymer matrix, when formed in this way, can slowly and safely release contraceptive hormone for weeks or months. when placed in the body. "
Testing with rats only assessed the blood levels of the hormone and did not try to determine if it could prevent pregnancy. "The aim was to show that we could allow the concentration of levonorgestrel to be above levels known to cause contraception in humans," Prausnitz explained.
In developing the experimental contraceptive microparticle patch, the researchers used earlier work to dissolve micronedle patches designed to carry vaccines in the body. A Phase I clinical trial of influenza vaccination using rapidly resolved microparticles has been conducted in collaboration with Emory University.
This study suggested that micronedle patches could safely be used to administer the vaccine. Because the microparticles are so small, they only enter the top layers of the skin and were not perceived as painful by the test subjects.
"We do not yet know how the contraceptive micronedle spots will work in humans," said Prausnitz. "Because we use a well-established contraceptive hormone, we are optimistic that patches will be an effective contraceptive. We also expect possible skin irritation at the patch application site to be minimal, but these expectations should be verified in clinical trials."
The contraceptives, tested on the animals contained 100 microns. To deliver an appropriate dose of levonorgestrel to a human, a larger patch that has been manufactured but not yet tested will be required. The researchers want to develop a patch that can be used once every six months.
"There is great interest in minimizing the number of health interventions that are needed," Prausnitz said. "Therefore, a contraceptive that lasts more than one month is desirable, especially in countries where women have limited access to health care. However, because micro-bills are small by definition, there are limits on how much substance can be incorporated into a micronedle plastic. "
Although mass production costs have not been determined, Prausnitz expects the contraceptive patches to be cheap enough for use in developing countries.
In addition to those already mentioned, the research team included Richard N. Terry of Georgia Tech and Jie Tang and Meihua R. Feng of the University of Michigan.
This publication was prepared under a subcontract funded by Family Health International (FHI 360) under Cooperation Agreement No. AID-OAA-1500045 funded by the US International Development Agency (USAID). The contents of this publication do not necessarily reflect FHI 360 or USAID's views, analysis or policies, nor are trade names, commercial products, or organizations endorsing FHI 360 or USAID.
Mark Prausnitz is an inventor of patents approved for companies that develop micronedle-based products, is a paid advisor for companies that develop micronedle-based products, and is a founder / shareholder of companies developing micronedle based products (Micron Biomedical). This potential conflict of interest has been revealed and managed by Georgia Tech and Emory University. CITATION: Wei Li et al., "Rapidly separable microneedle patch for sustained release or contraceptive," Nature Biomedical Engineering 2019).