Pharmacokinetics and Biological Effects of Ferromagnetic Nanocomposite in Rats with Sensitive and Ddp-Resistant Guerins Carcinoma
Abstract
ChekhunVF, LukianovaN Yu, TodorIM, StorchaiDM, BorikunTV, NaleskinaLA, Kusiak ÐP, PetranovskaAP and HorbykPP
Aim: To study nanocomposite-based conjugate of ferromagnet and cisplatin pharmacokinetic parameters and its therapeutic pathomorphosis in rats with sensitive and DDP-resistant Guerin’s carcinoma.
Material and Methods: The female Wistar rats with sensitive and DDP-resistant Guerin’s carcinoma received a nanocomposite-based conjugate of a ferromagnet and DDPonce at dose 3.5mg of DDP/kg intraperitoneally. All animals were anesthetized and samples of blood, tumour, liver and kidneys were collectedat 0.25, 0.5, 1, 3, 6 and 24h after the injection. Deposition of iron and platinum were measured using atomic absorption spectroscopy, AUC was calculated by trapezoidal method.
Results: In both sensitive and resistant strains of Guerin’scarcinonma, maximum concentriation of Pt in tumor tissue and blood serum was measured after at 1h after ingection of a nanocomposite-based conjugate of a ferromagnet and DDP. Pharmacokinetic studies found that agent accumulated 2.6 times more intensely in the DDP-resistanttumor tissue rather in sensitive. Introduction of studied agent in the therapeutic regimen leads to inhibiti on of the growth of DDP-resistant Guerin’scarcinoma, which is accompanied by the appearance of signs of medical pathomorphosis.
Conclusion: Pharmacokinetic studies have established that ferromagnetic nanocomposite accumulates more intensively in a resistant tumor and cause the most significant manifestations of therapeutic pathomorphosis compared to a sensitive tumor