Synergistic Effect of Toceranib and Nanohydroxyapatite as a Drug Delivery Platform—Physicochemical Properties and In Vitro Studies on Mastocytoma Cells

Abstract

A new combination of Toceranib (Toc; 5-[(5Z)-(5-Fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[2-(pyrrolidin-1-yl)ethyl]-1H-pyrrole-3-carboxamide) with nanohydroxyapatite (nHAp) was proposed as an antineoplastic drug delivery system. Its physicochemical properties were determined as crystallinity, grain size, morphology, zeta potential and hydrodynamic diameter as well as Toceranib release. The crystalline nanorods of nHAp were synthesised by the co-precipitation method, while the amorphous Toceranib was obtained by its conversion from the crystalline form during nHAp–Toc preparation. The surface interaction between both compounds was confirmed using Fourier-transform infrared spectroscopy (FT-IR), ultraviolet–visible spectroscopy (UV–Vis) and scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS). The nHAp–Toc showed a slower and prolonged release of Toceranib. The release behaviour was affected by hydrodynamic size, surface interaction and the medium used (pH). The effectiveness of the proposed platform was tested by comparing the cytotoxicity of the drug combined with nHAp against the drug itself. The compounds were tested on NI-1 mastocytoma cells using the Alamar blue colorimetric technique. The obtained results suggest that the proposed platform shows high efficiency (the calculated IC50 is 4.29 nM), while maintaining the specificity of the drug alone. Performed analyses confirmed that nanohydroxyapatite is a prospective drug carrier and, when Toceranib-loaded, may be an idea worth developing with further research into therapeutic application in the treatment of canine mast cell tumour.

Crystal structure of toceranib, C22H25FN4O2

“…The synchrotron powder pattern of this study matches the pattern measured by Sobierajska et al (2022) well enough to conclude that they represent the same material (Figure 4). The limited range and quality of the literature pattern makes the comparison difficult, but it seems that our sample is representative.…”

“…Comparison of the synchrotron pattern of toceranib (black) to that reported by Sobierajska et al (2022; green). The literature pattern, measured using Cu Kα radiation, was digitized using UN-SCAN-IT (Silk Scientific, 2013) and was converted to the synchrotron wavelength of 0.458963 Å using JADE Pro (MDI, 2022).…”

“…The only powder diffraction data of which we are aware was measured in the context of a study of toceranib/nanohydroxyapatite as a drug delivery platform (Sobierajska et al , 2022).…”

Nanohydroxyapatite Loaded with 5-Fluorouracil and Calendula officinalis L. Plant Extract Rich in Myo-Inositols for Treatment of Ovarian Cancer Cells

“…Due to its high surface-area-to-volume ratio and chemical composition, it favors chemical and physical modifications. Nanohydroxyapatite is an ideal platform for anticancer drug delivery [21,22], including, e.g., methotrexate [23] paclitaxel [24], toceranib [25], doxorubicin [26][27][28], and 5-fluorouracil [29]. HAp has also recently been used in randomized clinical trials in bone regeneration for its biocompatibility [30].…”