Abstract
In the present study, a nanoapatite-mediated delivery system for imatinib has been proposed. Nanohydroxyapatite (nHAp) was obtained by co-precipitation method, and its physicochemical properties in combination with imatinib (IM) were studied by means of XRPD (X-ray Powder Diffraction), SEM-EDS (Scanning Electron Microscopy-Energy Dispersive X-ray Spectroscopy), FT-IR (Fourier-Transform Infrared Spectroscopy), absorption spectroscopy as well as DLS (Dynamic Light Scattering) techniques. The obtained hydroxyapatite was defined as nanosized rod-shaped particles with high crystallinity. The amorphous imatinib was obtained by conversion of its crystalline form. The beneficial effects of amorphous pharmaceutical agents have been manifested in the higher dissolution rate in body fluids improving their bioavailability. Imatinib-to-hydroxyapatite interactions on the surface were confirmed by SEM images as well as absorption and FT-IR spectroscopy. The cytotoxicity of the system was tested on NI-1, L929, and D17 cell lines. The effectiveness of imatinib was not affected by nHAp modification. The calculated IC50 values for drug-modified nHAp were similar to those for the drug itself. However, higher cytotoxicity was observed at higher concentrations of imatinib, in comparison with the drug alone.
Highlights
Receptor tyrosine kinases (RTKs) are a large group of enzymes involved in a critical number of processes necessary for the proper functioning of both cells and organisms
We explored the possibility of combining nHAp with well-described tyrosine kinase inhibitors (TKIs), imatinib, as well as the effect on drug effectiveness
Amorphous substances, compared to their crystalline forms, possess a more irregular shape as well as higher internal energy and specific volumes, improving the dissolution and bioavailability of these compounds [33]. It means that the same drug could be used at a lower dose leading to a reduced risk of local side effects caused by unabsorbed materials and has a cost-saving effect
Summary
Receptor tyrosine kinases (RTKs) are a large group of enzymes involved in a critical number of processes necessary for the proper functioning of both cells and organisms. Since RTKs coordinate a wide variety of cellular functions, such as cell proliferation and differentiation, their activity must be regulated to prevent severe abnormalities in cellular functioning. Activated forms of the RTKs may be caused by an increase in the proliferation and growth of cancer cells, induce antiapoptotic effects, and promote angiogenesis and metastasis. Somatic mutations resulting in the constitutive activation of protein kinases are a common mechanism for cancer formation, often independent of ligand binding [1]. Receptor tyrosine kinases are key for anticancer targeted therapies. Many tyrosine kinase inhibitors (TKIs) have been designed so far, and many of them have clinical
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