When your mesothelioma doctor starts you on chemotherapy, the drug cocktail you take may include pemetrexed.
Pemetrexed is a pretty good therapeutic agent but it packs some unpleasant side effects.
Now, a research team from Japan appears to have developed a method to make pemetrexed work better against mesothelioma and perhaps with less discomfort.
The researchers’ technique involves encapsulating pemetrexed within a liposome bubble.
Liposomes are lab-made cells consisting of two outer layers and a hollow center — a bubble, in other words.
Scientists often fill the empty center of the bubble with various drugs. The loaded liposome then is used as a vehicle for delivering the drug directly to a designated cell target.
The liposome is outfitted with specific receptors that make sure it can find and attach itself to only the target cell. In this case, the target is mesothelioma.
Liposomal Pemetrexed Tested on Mesothelioma
Writing in a recent issue of the journal Biological and Pharmaceutical Bulletin, the researchers lamented that pemetrexed – whether used alone or with platinum analogs — typically can’t reach the tumor in sufficient concentrations to do as much good as it could.
Since liposomal encapsulation of other drugs has been shown in the past to improve effectiveness against other diseases, the researchers thought they’d try out the technique with pemetrexed.
Step One involved testing for the best type of liposome to use. They come in two types – one is classified as fluid, the other as solid.
The researchers found that the fluid version worked very well, but the solid type did not.
They wrote that the way the pemetrexed was released from the fluid version upon delivery to the target was notably efficient – so much so that it resulted in potent cytotoxicity against the MSTO-211H cell line of mesothelioma.
At least it did in lab dishes, which is where all this experimenting occurred.
By contrast, the solid type of liposome tended to cling onto the pemetrexed within and thereby prevented cytotoxicity from taking place.
The researchers also discovered that the process of loading pemetrexed into the individual liposomes was made significantly easier if the liposomes’ membranes contained cholesterol.
Liposomes between 50 nanometers and 150 nanometers appear to be the ideal size for carrying pemetrexed, they determined.
Popular Mesothelioma Chemotherapy Drug
Pemetrexed is a popular mesothelioma chemotherapy drug because it can attack a cell at more than one point of vulnerability, the researchers explained.
Specifically, it can target at least three different enzymes involved in the synthesis of purine and pyrimidine, which mesothelioma cells need in order to function.
That gives pemetrexed a big advantage over other mesothelioma chemotherapy drugs such as methotrexate, which can only attack one enzyme involved in making purine and pyrimidine.
But the advantage is lost because pemetrexed can’t reach those enzyme targets in sufficient quantity when delivered the usual way – by infusion, for example.
The researchers are convinced now that use of a liposome delivery system can restore that advantage.
And as a bonus, “liposomal systems allow increased preferential accumulation of the encapsulated agent in tumor site with a concomitant decrease in the extent and types of non-specific toxicities,” they wrote.
The researchers are from the University of Tokushima. Their article is entitled, “Liposomal Pemetrexed: Formulation, Characterization and In Vitro Cytotoxicity Studies for Effective Management of Malignant Pleural Mesothelioma.”
