Researchers at Oregon State University have developed a drug delivery system that is intended to treat ectopic pregnancy. Often occurring in the fallopian tubes, ectopic pregnancies are non-viable and are the leading cause of maternal death in the first trimester. A drug called methotrexate can be administered to end the pregnancy, but can cause serious side-effects at the concentrations required. These researchers designed a nanoparticle delivery vehicle for methotrexate that can release its drug payload near where it is needed by responding to glutathione, a tripeptide that is present in high concentrations in placental cells. The technology means that significantly lower doses of methotrexate can be used to treat ectopic pregnancy, reducing the chance of side-effects.
The researchers behind this latest study report that between 1% and 2% of pregnancies worldwide are ectopic. These pregnancies nearly always implant in the fallopian tubes, where they can cause serious damage resulting in hemorrhage, and are the leading cause of maternal death in the first trimester. Methotrexate can be used to treat ectopic pregnancy, and works by inhibiting the ability of embryonic cells to divide.
However, at the required doses, the drug can cause serious side effects, including kidney damage, nausea, vomiting, diarrhea, and lung disease. Moreover, methotrexate fails to successfully treat ectopic pregnancy in approximately 10% of cases, largely due to a lack of the drug reaching the target site. These issues prompted these researchers to develop a more targeted way to deliver methotrexate, meaning increased concentrations in the target tissue, and reduced exposure elsewhere.
“Developing drugs able to target specific locations in the body remains one of biomedicine’s greatest challenges,” said Olena Taratula, a researcher involved in the study. “Most of the drugs prescribed today, including methotrexate, have no means of working only on specific tissues or cells. When drugs affect healthy cells, it can drastically reduce a patient’s quality of life — think of the severe effects of chemotherapy like hair, loss of the lining of the gut, ulcer formation, nausea, etc.”
Their solution involves using polymersomes, which are synthetic versions of vesicles such as liposomes. Polymersomes, though, are made with polymers rather than lipids. However, these nanoparticles incorporate a clever mechanism to ensure that they release their drug payload exactly where it is required. They are responsive to glutathione, a tripeptide that is found in high concentrations in placental cells, allowing them to release the drug in the vicinity of the ectopic pregnancy. This will hopefully lead to very targeted delivery of the drug to treat the condition while being gentle on the rest of the woman.
Study in journal Small: Glutathione?Responsive Methotrexate Polymersomes for Potential Management of Ectopic Pregnancy