Colleague of the University of Nova Gorica on the Key Improvements in the Preparation of a Known Drug in Cancer Chemotherapy

Date of publication: 9. 7. 2004
Achievements

A colleague of the University of Nova Gorica, Prof. dr. Iztok Arčon, reported with his colleagues in a recently published article on the key improvements in the preparation of a known drug in cancer chemotherapy - cisplatin, which substantially increases the drug's effectiveness in treatment. The research was carried out in co-operation between the University of Nova Gorica, the American company Liposome Consultations from California, the Jožef Štefan Institute, and the Department of Physics at the Faculty of Mathematics and Physics of the University of Ljubljana.

Determining the structure of cisplatin in liposome vesicles for cancer chemotherapy.

A colleague of the University of Nova Gorica, Prof. dr. Iztok Arčon, reported with his colleagues in a recently published article on the key improvements in the preparation of a known drug in cancer chemotherapy - cisplatin, which substantially increases the drug's effectiveness in treatment. The research was carried out in co-operation between the University of Nova Gorica, the American company Liposome Consultations from California, the Jožef Štefan Institute, and the Department of Physics at the Faculty of Mathematics and Physics of the University of Ljubljana.

In an American laboratory the, now late, Slovene scientist, Dr. Danilo Lasič developed a procedure for inserting cisplatin into liposome vesicles, the diameter of which does not exceed a ten thousandth of a millimetre (100 nanometres). With this he tried to substantially improve the effectiveness and selectivity of the drug, and reduce its side effects. In many cases a sufficiently high concentration of the drug and consequently its effectiveness can only be achieved with the insertion into microscopic liposome vesicles. An effective and stable encapsulation of the drugs into liposomes is one of the most demanding tasks in the preparation of the drug. In many instances it cannot be successfully solved. In the case of the insertion of cisplatin the fact that the solubility of the drug in water increases substantially at higher temperatures was taken advantage of. Hence the insertion into the liposomes was carried out at a temperature of 60°C, which enables an eight times higher concentration than at room temperature.

The fundamental unresolved question was in what state is the drug within the liposome after the preparation cools off to room temperature and the cisplatin solution in the liposomes becomes supersaturated by eight times. Is a drug stored in such a way still usable and is it chemically stable? It would be possible for the drug in the liposome to simply crystallise at such a high concentration, or react with the lipid walls within the liposome, or even decompose, which would destroy its chemotherapeutic function.

A decisive answer to these questions was provided by the X-ray spectroscopic analyses of Prof. dr. Iztok Arčon, which he carried out with his colleagues at the synchrotron laboratory HASYLAB, DESY in Hamburg. With the use of an EXAFS X-ray absorption method, which enables the observation of the immediate surroundings of individual types of atoms in a substance, he has demonstrated that the cisplatin molecules within the liposomes are chemically stable and do not decompose. Furthermore, on the basis of these structural measurements he has shown that the drug, trapped within a liposome, does not crystallise, but is preserved in the form of an aqueous solution supersaturated by eight times; therefore, in a form that is optimal for effective treatment.