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Researchers find evidence that ‘fat’ may be the answer to delivering a mesothelioma drug more effectively

14 October 2015

A team of drug researchers working on a way to make a mesothelioma treatment more effective is developing a fat-based coating for a drug, which may help improve outcomes for sufferers.

A team based in Zagazig University in Egypt and Tokushima University in Japan have developed a fat-based coating for the antifolate drug pemetrexed, which is a chemotherapy drug used to treat non-small cell lung cancer and pleural mesothelioma. At the moment, pemetrexed is used for malignant mesothelioma and most patients will receive it at some point during their treatment plan.

Image courtesy of ponsulak at FreeDigitalPhotos.net

Like all mesothelioma therapies, pemetrexed is only partly effective. One of the reasons why is because it can only be used in limited doses to avoid serious side effects.

The main side effects

  • Pemetrexed can reduce the number of white blood cells in your blood, which increases the risk of infection. When a patient’s white blood cells count is low, it is called neutropenia.
  • The drug can reduce the number of platelets in your blood, which are there to help the blood to clot. Patients can suffer nosebleeds, bleeding gums, blood spots or rashes on the skin.
  • Pemetrexed can also contribute to anaemia, which occurs when a person has a low number of red blood cells. These cells carry oxygen around the body and when they are low a patient may feel tired and breathless.
  • The drug can also make a patient feel sick. This may happen in the first few days after chemotherapy and anti-sickness drugs have to be used to control sickness.
  • It can cause a loss of appetite during treatment.
  • Pemetrexed can make the mouth sore and encourage ulcers, which can lead to infection in the mouth.
  • Diarrhoea can also be a side effect, but drugs can be used to control the condition.
  • Feeling very tired is a common side effect. It is often worse towards the end of treatment and for some weeks after.
  • Pemetrexed can affect the skin and cause a rash that may be itchy. Any changes to skin are usually temporary and improve when treatment finishes.
  • The drug can cause numb or tingling hands or feet, which is caused by the effect of pemetrexed on the nerves. The condition is called peripheral neuropathy and it can make it hard to do fiddly tasks like shoelaces and buttons.

Less common side effects can include eye problems, hair loss and constipation. Pemetrexed is often used with other chemotherapy drugs and a patient can suffer a number of other side effects. The side effects can be controlled with other drugs and by lowering the dose of the drug, but this reduces the effectiveness of Pemetrexed.

Image courtesy of Photokanok at FreeDigitalPhotos.net

Avoiding side affects

The research team have developed a new way of delivering the drug by wrapping molecules of pemetrexed in bubble-like structures called liposomes. These structures are made from fat molecules that are attracted to mesothelioma cells. Potentially the ‘fat bubbles’ can deliver pemetrexed directly to the cancer cells with fewer side effects.

After tests in the laboratory, the team are now testing liposomal pemetrexed on live mice infected with mesothelioma, before human trials can begin. The new study uses different groups of mice that are given liposomal pemetrexed with different levels of liposomes (the ‘fat’ coating). All the different levels tested stayed in the plasma (blood) longer than liposomal-free pemetrexed and improved the amount of the drug that collected in the mesothelioma tumours. The pemetrexed coated in a fast-release liposomal suppressed tumour growth and triggered cell death better than slow-release and liposomal-free combinations.

Noah Essam Eldin of Zagazig University said in the European Journal of Pharmaceutical Sciences: “Our results clearly emphasise the therapeutic efficacy of liposomal pemetrexed over free pemetrexed in conquering aggressive solid tumours such as malignant mesothelioma.”

Mesothelioma is a dreadful terminal lung cancer caused by exposure to asbestos dust and fibres. The cancer usually develops in the lining of the lungs between 10 and 50 years after exposure.

Liposomal chemotherapy drugs are already being used to treat other conditions such as metastatic breast cancer, macular degeneration, hepatitis A, fungal infections and influenza.

Further reading:

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


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