Pharmaceutical researchers working on a way to make the most popular mesothelioma drug more effective have found more evidence that fat may be the answer.
The team at Zagazig University in Egypt and Tokushima University in Japan have developed a fat-based coating for the antifolate drug pemetrexed (Alimta) that may help improve outcomes for patients. Pemetrexed is currently the only drug approved specifically to treat malignant mesothelioma and most patients will receive it at some point. Even so, like most mesothelioma therapies, pemetrexed is only marginally effective, in part because the dose has to be limited to avoid serious side effects.
The new drug delivery system was designed to get around this problem by encapsulating molecules of pemetrexed in tiny bubble-like structures called liposomes. These “bubbles” are made of fat molecules and are designed to be attracted to mesothelioma cells, making them an ideal way to deliver cancer-fighting drugs like pemetrexed with fewer side effects.
Earlier this year, the same research team tested the liposomal pemetrexed in mesothelioma cells in the lab. Now, they have moved on to live mice infected with mesothelioma in order to fine-tune the process before trying it on human patients.
In the new study, different groups of sick mice were given liposomal pemetrexed with different levels of membrane fluidity. Both formulations stayed in the plasma longer than unencapsulated pemetrexed and improved the amount of pemetrexed that accumulated in the mesothelioma tumors. But the pemetrexed encapsulated in the the most fluid phospholipid suppressed tumor growth and triggered apoptosis (cell death) even better than the other formulation.
“Our results clearly emphasize the therapeutic efficacy of liposomal pemetrexed over free pemetrexed in conquering aggressive solid tumors such as malignant mesothelioma,” writes lead author Noah Essam Eldin of Zagazig University in the European Journal of Pharmaceutical Sciences.
Liposomal chemotherapy drugs are already being used to treat some other conditions including metastatic breast cancer, macular degeneration, hepatitis A, fungal infections and influenza.
Eldin, NE, “Encapsulation in a rapid-release liposomal formulation enhances the anti-tumor efficacy of pemetrexed in a murine solid mesothelioma-xenograft model”, September 25, 2015, European Journal of Pharmaceutical Sciences, Epub ahead of print