Bones are the fourth most frequent site of metastasis from malignant tumors, including breast cancer, prostate cancer, melanoma, etc. The bioavailability of bone tissue for chemotherapy drugs is extremely low. This requires a search for new approaches of targeted drug delivery to the tumor growth zone after surgery treatment. The aim of this work was to develop a method for octacalcium phosphate (OCP) bone graft functionalization with the cytostatic drug cisplatin to provide the local release of its therapeutic concentrations into the bone defect. OCP porous ceramic granules (OCP ceramics) were used as a platform for functionalization, and bisphosphonate zoledronic acid was used to mediate the interaction between cisplatin and OCP and enhance their binding strength. The obtained OCP materials were studied using scanning electron and light microscopy, high-performance liquid chromatography, atomic emission spectroscopy, and real-time PCR. In vitro and in vivo studies were performed on normal and tumor cell lines and small laboratory animals. The bioactivity of initial OCP ceramics was explored and the efficiency of OCP functionalization with cisplatin, zoledronic acid, and their combination was evaluated. The kinetics of drug release and changes in ceramics properties after functionalization were studied. It was established that zoledronic acid changed the physicochemical and bioactive properties of OCP ceramics and prolonged cisplatin release from the ceramics. In vitro and in vivo experiments confirmed the biocompatibility, osteoconductivity, and osteoinductivity, as well as cytostatic and antitumor properties of the obtained materials. The use of OCP ceramics functionalized with a cytostatic via the described method seems to be promising in clinics when primary or metastatic tumors of the bone tissue are removed.

Methods of quantitative determination of the platinum content in high-salt solutions have been developed using atomic absorption spectroscopy (AAS). Definitions were carried out for small volume bioassays during the research of functionalization of calcium phosphate substitute materials with anticancer drug, cisplatin. The conditions for the determination of Pt in the flame were optimized. The effects of the cisplatin matrix solutions, salt components and concentrations on the Pt absorption value were found out. The relevance of application of the flame version of the AAS method was shown in order to determine the platinum content in high-salt solutions, over 200 g/l, without matrix separation in a wide range of Pt concentrations from 0.1 to 50 µg/ml. This issue was targeted through the estimation of efficiency of Pt-containing drug incorporation and its dynamics release as an application method in the development of drug delivery systems for bone tumors treatment.