Development of a parenterally administrable hydrosol preparation of the "third generation platinum complex" [(+/-)-1,2-bis(4-fluorophenyl)ethylenediamine]dichloroplatinum(II). Part 1. Preparation and studies on the stability and antitumor activity

The development of a galenical formulation for poorly water soluble dichloroplatinum(II) complexes suitable for the parenteral administration in cancer chemotherapy is described. The procedure, which we elaborated for [(+/-)-1,2-bis(4-fluorophenyl)ethylenediamine]dichloroplatinum(II) (rac-4F-PtCl2), is based on the reaction of a soluble diaquaplatinum(II) salt with sodium chloride in water in the presence of pluronic F 68 as stabilizer and results in a sufficiently stable colloidal solution (i.e. hydrosol). In contrast to the poorly water soluble synthetic rac-4F-PtCl2, which was ineffective towards the hormone sensitive MXT-M-3.2 breast cancer of the mouse, its hydrosol formulation proved to be highly active and was very well tolerated.