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Information × Registration Number 0215U000035, 0114U001662 , R & D reports Title Development of technology for ferroplat synthesis and its preclinical testing popup.stage_title Head Chekhun Vasyl Fedorovych, Registration Date 15-01-2015 Organization R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology popup.description2 Aim: development of technology for synthesis of "ferroplat" antitumor drug, which is specific against tumor cells and preclinical studies of its antitumor activity. Methods: laser confocal spectroscopy, roentgeno-strucyural analysis, transparent electron microscopy, EPR-spectroscopy, atom-adsorption spectroscopy, computer modelling, cell cultivation in vitro, experimental oncology methods (tumor transplantation, tumor growth dynamics and metastases development, length of experimental animals' survival periods), cytomorphological, biochemical, statistical. Results: For the first time in Ukraine we developed a standartized method for synthesis of antitumor drug "ferroplat", which contained magnetic fluid nanoparticles and cisplatin. The acquired size distributions of nanoparticles characterized the synthesised composition as monodispersion with average particle size of 32,7 nm. Results of electron-microscopy studies suggested that this colloid system was monodisperse and did not form conglomerates. Atom-emission spectrometry data showed Fe3O4 concentration in ferroplat was 3 mg/ml, while concentration of Pt2+ - 0,4 mg/ml. Vibration magnitometry charactrized ferroplat magnetic features. They did not differ from those of magnetic fluid. We determined parameters of ferroplat pharmacological safety. LD50 for ferroplat was equal 10,0 ± 0,8 mg/kg, and MTD = 4,0 ± 0,3 mg/kg, while LD50 and MTD for officinal cisplatin Ebewe were 7,8 ± 0,6 mg/kg and 6,1 ± 0,5 mg/kg. The acquiged data pointed on abscence of significant differences in ferroplat and cisplatin LD50. At the same time, we found significant changes in MTD for these drugs, resulting in higher therapeutic width for ferroplat compared to cisplatin and advanteges for its use in therapy in future. Studies of ferooplat cumulative toxicity showed significant increase of urine and creatinine levels in serum of studied animals, while general blood indices were similar between control animals and those which received cumulative dose of ferroplat . Preclinical studies on the models of ascetic and solid tumors proveed that antitumor and antimetastatic activity of ferroplat did not differ from those of officinal cisplatin. At hte same time we showed that ferroplat is much more active against tumors which were resistant to cisplatin. Fe found that toxic effects of ferroplat correspond to those of cisplatin. The acquired data suggest that use of ferroplat in schemes of antitumor therapy would allow increase of cisplatin selectivity and overcome drug resistance. Product Description popup.authors Башицька Наталія Василівна Горбик Петро Петрович Лук'янова Наталія Юріївна Мельник Наталія Миколаївна Петрановська Алла Леонідівна Тодор Ігор Миколайович Трембач Людмила Валентинівна Чехун Василь Федорович popup.nrat_date 2020-04-02 Close