Institute of Low Temperature and Structure Research, Polish Academy of Sciences, Okolna 2, 50-422 Wroclaw, Poland.
Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Norwida 27B Street, A7 Building, 50-375 Wroclaw, Poland.
Molecules. 2020 Oct 9;25(20):4602. doi: 10.3390/molecules25204602.
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 IC 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.
在本研究中，提出了一种纳米磷灰石介导的伊马替尼递送系统。通过共沉淀法获得纳米羟基磷灰石（nHAp），并通过 X 射线粉末衍射（XRPD）、扫描电子显微镜-能谱（SEM-EDS）、傅里叶变换红外光谱（FT-IR）、吸收光谱和动态光散射（DLS）技术研究了与伊马替尼（IM）结合的 nHAp 的物理化学性质。所得的羟基磷灰石被定义为具有高结晶度的纳米棒状颗粒。通过将其晶型转化得到无定形伊马替尼。无定形药物的有益作用体现在更高的在体液中的溶解速率，从而提高其生物利用度。SEM 图像、吸收光谱和 FT-IR 光谱证实了伊马替尼与羟基磷灰石表面的相互作用。在 NI-1、L929 和 D17 细胞系上测试了该系统的细胞毒性。nHAp 修饰并未影响伊马替尼的有效性。药物修饰的 nHAp 的计算 IC 值与药物本身的 IC 值相似。然而，与单独使用药物相比，在更高浓度的伊马替尼下观察到更高的细胞毒性。
