Pemetrexed (Alimta) was approved for the treatment of pleural mesothelioma in 2004 and remains the only drug specifically for the treatment of this intractable cancer. Because of its toxicity, pemetrexed can’t be given in very high doses and usually has to be combined with another drug, such as cisplatin, when it is given to mesothelioma patients. Unfortunately, even this “gold standard” drug treatment is only effective about 40 percent of the time.
But a new drug delivery system may boost the effectiveness of pemetrexed and improve outcomes for pleural mesothelioma patients. Researchers in Egypt and Japan are experimenting with delivering pemetrexed to the body using tiny bubble-like structures called liposomes.
Liposomes are artificially-prepared “bubbles” or vesicles with a membrane similar in makeup to a cell membrane. They can be designed to be more attracted to certain kinds of tissues – such as cancer tissue – making them an ideal way to target the delivery of cancer-fighting drugs like pemetrexed.
In a newly-published study, the researchers experimented with several different kinds of liposomes to carry pemetrexed directly into mesothelioma cells in the lab. The most effective liposomes were fluid-filled and had membranes with a higher concentration of cholesterol and other lipids. According to the investigators, these had a “potent in vitro cytotoxicity” against a top human mesothelioma cell line.
In a summary of the findings in the medical journal Biological & Pharmaceutical Bulletin, author Noah Essam Eldin of Zagazig University in Egypt writes, “These results suggest that encapsulation of pemetrexed within ‘fluid’ liposomes might represent a novel strategy to enhance the therapeutic efficacy of pemetrexed while minimizing the side effects encountered by the non-selective delivery of free [non-liposomal] pemetrexed to various body tissues.”
Liposomal drugs are already being used to treat metastatic breast cancer as well as a range of other conditions including hepatitis A, fungal infections, influenza, and macular degeneration.
Essam Eldin, N, et al, “Liposomal pemetrexed: formulation, characterization and in vitro cytotoxicity studies for effective management of malignant pleural mesothelioma”, 2015, Biological and Pharmaceutical Bulletin, pp. 461-469.