Trading water for oil to enhance cancer treatments

Professor Clive PrestidgeNew technologies created by Professor Clive Prestidge and his team are showing promising results for reformulating current cancer therapies into improved oral doses that can be taken at home. The research is currently being applied to develop new bowel and prostate cancer medicines.

"One of the major problems in developing oral medicines is poor water-solubility—which means only tiny amounts of the drug can be absorbed across the gut into the body," says Professor Prestidge, who leads a pharmaceutical research team in the new UniSA Cancer Research Institute.

More than 40% of currently prescribed pharmaceutical drugs have this problem, so high doses must be taken in order for the therapeutic level to be reached.

"Results from our research on a common bowel cancer treatment are showing that we have an opportunity to improve current cancer therapies, and in turn the patient's quality of life."

Professor Clive Prestidge, a leading Pharmaceutical Scientist in the field of controlled-release drug delivery.

Oil-based (lipid) formulations have been suggested as an alternative carrier for these difficult to absorb drug molecules; while the oil does help drugs absorb easier and cross biological barriers (such as the membrane that lines the intestine), until now formulations have proven largely unstable.

"The LipoCeramicTM technology we developed is overcoming this instability as we can pre-dissolve the drug in oil and then encapsulate it in a special nanoporous silica substance that controls our gut's natural enzymes to maximise absorption into the body," he says.

"We are also using chemistry to make chemotherapy drugs oily, and delivering them by nanomedicines, which further helps their absorption and can reduce toxic side effects.

"For example, for advanced or recurrent bowel cancer patients who attend hospital to be injected with a cocktail of drugs including Irinotecan. It is feasible that we could not only convert this injected drug into a 'take at home orally dosed medicine', but also reduce the life threatening gut toxicity by controlling the metabolism and bio-distribution.

"Preclinical results thus far with our modified Irinotecan are very promising—we have managed to reach the ideal therapeutic range over a sustained period and without reaching the higher toxic levels, which is ideal in cancer treatments.

"When you think about the fact that it costs more than $1billion to get a new drug to market, it makes sense that we find ways to improve our current medications."

Reworking the formula for better prostate cancer therapy

Hayley SchultzAnother project within Professor Prestidge’s team is showing similarly promising results for improving a common androgen depletion therapy (ADT) for advanced prostate cancer.

Hayley Schultz, UniSA PhD Candidate, is exploring how to load more drug into the tablets to create a better ADT formulation.

“Testosterone stimulates prostate cancer cells to grow, so patients are often given an ADT that blocks its production,” says Schultz.

“A particularly complex ADT oral treatment is used in castrate resistant prostate cancer called abiraterone acetone. It is prescribed in very high doses because only about 5% of the drug is absorbed due to its poor water-solubility.”

"This research is showing promise for improving treatment for an advanced prostate cancer."

Hayley Schultz, PhD Candidate.

“It is also highly sensitive to the pharmaceutical food effect, so if a patient eats food too close to taking their tablets they can absorb greater, unknown and potentially toxic levels of the drug. This is because the drug dissolves much better in the oily or fatty food digesting in the gut.

“My new oil based formulation has the potential to deliver more of the drug by mimicking this food effect. The oil helps the drug to dissolve and absorb easier in the gut, resulting in high and consistent amounts of drug entering the bloodstream regardless of whether the patient has eaten close to taking the dose.

“This means that we can reduce the dose as more of the drug will be absorbed—which is significant for these patients as they have such a difficult therapy regime that requires them to remember to fast every day and then take large quantities of tablets.

“Ultimately, I would like to see this formulation provide better drug delivery for many different types of pharmaceutical treatments.”