In vitro tests demonstrate effectiveness of new technique
The doxorubicin was added to the cell cultures both directly and encapsulated in the nano-carriers
Many cancer patients suffer from the intense effects that accompany chemotherapy, such as hair loss, nausea, vomiting, fatigue, loss of appetite, loss of eye lashes and eye brows, and susceptibility to infection. Scientists at the Fraunhofer Institute for Applied Polymer Research (IAP) in Potsdam, Germany, have developed a new technique to deliver high doses of cytostatic agents that may be easier on patients.
The researchers have been investigating the use of nanoparticles as vehicles for the anticancer agents. Since the particles resemble cells on account of their structure, they are suited to steering pharmaceutical substances to the tumour selectively, docking there, and efficiently eliminating the malignant cells.
The researchers have decided to use hydrophobic, water-insoluble lipid vesicles as the tiny pharmaceutical carriers measuring 200-250nm. They are biologically degradable and disintegrate in the body after deployment. Polymers are used to stabilize the nano-envelope (known as the vesicle), which is furnished with molecules highly specific to and recognised by tumor cells.
The vesicle is constructed similarly that of a cell. The scientists load these carriers with doxorubicin, together with the surfactant sodium tetradecyl sulfate (STS) that helps the active agent to be absorbed better.
The researchers have already been able to prove the efficacy of their approach in laboratory tests. 'We utilised both a cervical cancer strain (HeLa) and cancer of the large intestine (HCT116) for our in vitro tests,' explained Dr Joachim Storsberg. 'They each react very differently to doxorubicin. HCT116 cells are sensitive to the substance, in contrast to HeLa cells.
'We ran the experiments with pharmacologically relevant dosages, used by clinicians. The doxorubicin was added to the cell cultures both directly and encapsulated in the nano-carriers.'
Storsberg developed the new therapy jointly with Dr Christian Schmidt and Nurdan Dogangüzel from IAP in close collaboration with colleagues from the pharmaceutical sciences, Professor Mont Kumpugdee-Vollrath and Dr J P Krause from Beuth University of Applied Sciences in Berlin.
After three days, 43.3% of the HeLa cells survived a dose of unencapsulated, 1 micromolar (µM) doxorubicin. When the active agent was introduced via encapsulated vesicles, only 8.3% of the malignant HeLa cells survived. 'The pharmaceutical substance in the nano-envelopes was five times more effective,' said Storsberg.
This could also be observed in the tests with the intestinal cancer cells: in this experiment, 46.5% of the HCT116 cells survived a dose of 0.1µM doxorubicin after two days, while only 13.3% of the malignant tumor cells failed to be eliminated by administering the active agent in encapsulated form. 'With nanoparticles as carriers, a more effective and simultaneously lower dosage is possible. This way, and with a targeted delivery of the active agent, the healthy cells are are likely to be spared and the side effects will be minimised,' sais Storsberg.
However, the encapsulation material is effective only when combined with the active agent. The unloaded nano-carrier does not attack the sensitive HCT116 cells. Using their methodology, Storsberg and his team can investigate how effectively an encapsulated pharmaceutical substance acts, as well as how ‘toxic’ the actual nanomaterial is. 'That has not been feasible to date,' he emphasised.
A series of clinical tests with cancer patients will be set up only if these observations are confirmed in in vivo experiments.