A recent study conducted by researchers at the OSU College of Pharmacy and Oregon Health & Science University has shown promising results in using low-dose nanoparticles of methotrexate to effectively end ectopic pregnancies. The findings, published in the journal Small, highlight the potential of these nanoparticles, known as polymersomes, to reduce the side effects of the drug while increasing its efficacy.
Ectopic pregnancies, which occur outside the uterus, are non-viable and the leading cause of maternal death in the first trimester. Methotrexate, commonly abbreviated as MTX, is a commonly used drug for ending ectopic pregnancies but has a failure rate of over 10% due to its inability to accumulate properly at the implantation site. This is where the polymersomes come into play.
The researchers used a mouse model to demonstrate that methotrexate administered via polymersomes effectively ends pregnancy at a comparatively low dose. Methotrexate works by causing embryonic cells to stop dividing, but even when successful, it often comes with a range of potential negative side effects such as nausea, vomiting, diarrhea, elevated liver enzymes, kidney damage, and lung disease. By reducing the dosage, the scientists hope to decrease these side effects and improve the drug’s efficacy.
According to the authors of the study, approximately 2% of all pregnancies in the United States, and between 1% and 2% worldwide, are ectopic, amounting to roughly 100,000 ectopic pregnancies annually in the US alone. The majority of these implantations occur in the fallopian tubes, putting women at risk of hemorrhage and death.
Olena Taratula, one of the lead researchers involved in the study, highlighted the importance of developing drugs that can specifically target certain tissues or cells in the body. Many drugs, including methotrexate, lack the ability to selectively work on specific locations, causing severe side effects in healthy cells. Taratula and her team sought to overcome this challenge by exploring the use of polymersomes to package methotrexate, allowing it to specifically target only embryonic cells.
Polymersomes are synthetic versions of liposomes, which are hollow spheres found in all living cells. The scientists developed a polymersome that responds to high concentrations of a substance called glutathione in placental cells. By loading methotrexate into these polymersomes, the drug remains inactive until triggered by glutathione, ensuring that it acts only on the targeted cells.
In experiments involving mice, a dose of methotrexate delivered via polymersomes successfully induced the end of pregnancy, while the same dose of methotrexate alone did not. In fact, to achieve the same therapeutic efficacy with methotrexate alone, a sixfold increase in the dosage was required. Furthermore, mice that had their pregnancies ended by methotrexate-loaded polymersomes were able to conceive again and give birth to healthy offspring.
The study was a collaborative effort between researchers from the OSU College of Pharmacy, Oregon Health & Science University, and the National Institutes of Health. The development of the polymersomes and the research itself were supported by funding from these institutions.
Taratula and her team are continuing their research into other types of nanoparticles for diagnosing and ending ectopic pregnancies. They previously collaborated on the development of a light-sensitive nanoparticle for this purpose and recently received a $3 million grant from the National Institutes of Health to develop a magnetic nanoparticle platform. Taratula believes that magnetic nanoparticles could be even more effective than light-sensitive ones due to their deeper tissue penetration capabilities.
This groundbreaking research provides hope for women facing ectopic pregnancies, offering a potential solution to reduce side effects and increase the efficacy of methotrexate. As scientists continue to explore the field of targeted drug delivery, advancements like these have the potential to revolutionize the way medications are administered in various medical conditions, improving patient outcomes and quality of life.
Sources:
https://onlinelibrary.wiley.com/doi/10.1002/smll.202003825
https://news.ohsu.edu/2021/11/23/osu-ohsu-team-finds-nanoparticles-could-make-ectopic-pregnancy-drug-more-effective
