Delivery of anti-cancer and anti-depression doxepin drug by nickel oxide nanoparticles originated from the Cressa nudicaulis plant extract

Abstract

In this research, the extract of Cressa nudicaulis plant has been used as a natural reducing agent in order to prepare stable nickel oxide nanoparticles (NiO NPs) using an aqueous solution of nickel(ii) nitrate under the sol-gel method. Additionally, NiO NPs were distinguished using FT-IR (Fourier transform infrared spectroscopy), XRD (X-ray diffraction), FESEM (field-emission scanning electron microscopy), EDS (energy-dispersive X-ray spectrometry), TEM (transmission electron microscopy), and UV-Vis (ultraviolet-visible spectroscopy) techniques. The integrated NiO NPs were loaded with doxepin drug as an effective medication for head and neck cancer as well as depression. Then, the ideal loading circumstances such as pH of the medium, response time, and amount of nanoparticles were assessed to attain that pH 6, time 12 h, and nanoparticle amount of 0.02 g are optimal to accomplish the best drug loading of around 68%. The drug release properties of drug-loaded NiO were also investigated at pH 6.5 and 37 °C. This study showed that ∼73% of the loaded drug was released after 80 h. Therefore, the introduced delivery system shows sufficiently long targeted-release properties. Besides, the MTT experiment was utilized to investigate the cytotoxicity of NiO NPs on the human hepatocellular carcinoma cell line Huh-7.

Fig. 1. The FT-IR spectra of (a) doxepin and (b) NiO nanoparticles as well as doxepin-loaded NiO.

Fig. 2. (a) FESEM and (b) TEM images of NiO nanoparticles.

Fig. 3. EDS analysis of NiO nanoparticles.

Fig. 4. The UV-Vis spectrum of NiO nanoparticles.

Fig. 5. The XRD pattern of NiO nanoparticles.

Fig. 6. Drug loading (%) under three different conditions. Effect of (a) pH, (b) reaction time, and (c) amount of NiO NPs.

Fig. 7. TGA profile of doxepin-loaded NiO NPs.

Fig. 8. The UV-Vis spectra of (a) NiO nanoparticles, (b) doxepin, and (c) drug-loaded NiO NPs.

Fig. 9. UV-Vis spectral changes of doxepin with time in the presence of NiO NPs.

Scheme 1. A schematic representation describing the interaction of doxepin with NiO nanoparticle.

Fig. 10. The in vitro release of doxepin from NiO-Dox at 37 °C in PBS buffer (pH 6.5).

Fig. 11. The cell viability of cancer Huh-7 cell line against (a) NiO NPs and (b) drug-loaded NiO NPs (n = 3, P < 0.001) using the MTT test.