Use of Saponinosomes from Ziziphus spina-christi as Anticancer Drug Carriers

Zahra Nazemoroaya; Mohsen Sarafbidabad; Athar Mahdieh; Darya Zeini; Bo Nyström

doi:10.1021/acsomega.2c03109

Use of Saponinosomes from Ziziphus spina-christi as Anticancer Drug Carriers

ACS Omega. 2022 Aug 4;7(32):28421-28433. doi: 10.1021/acsomega.2c03109. eCollection 2022 Aug 16.

Authors

Zahra Nazemoroaya¹, Mohsen Sarafbidabad², Athar Mahdieh^{3

4}, Darya Zeini^{4

5}, Bo Nyström⁴

Affiliations

¹ Student Research Committee, School of Pharmacy, Shahid Beheshti University of Medical Sciences, 19839-63113 Tehran, Iran.
² Department of Biomedical Engineering, Faculty of Engineering, University of Isfahan, 81746-73441 Isfahan, Iran.
³ School of Pharmacy, Department of Pharmaceutics, University of Oslo, P.O. Box 1068, Blindern, N-0316 Oslo, Norway.
⁴ Department of Chemistry, University of Oslo, P.O. Box 1033, Blindern, N-0315 Oslo, Norway.
⁵ Laboratory of Neural Development and Optical Recording (NDEVOR), Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1103, N-0317 Oslo, Norway.

Abstract

Saponins are plant glycosides with different structures and biological activities, such as anticancer effects. Ziziphus spina-christi is a plant rich in saponin, and this compound is used to treat malignant melanoma in the present study. Nanophytosomes can be used as an advantageous nanodrug delivery system for plant extracts. The aim of this work is to use the saponin-rich fraction (SRF) from Z. spina-christi and prepare SRF-loaded nanophytosomes (saponinosomes) and observe the in vitro and in vivo effects of these carriers. First, the SRF was obtained from Z. spina-christi by a solvent-solvent fractionation method. Then, Fourier transform infrared (FTIR) analyses were performed to confirm the presence of saponins in the extracted material. Subsequently, the saponinosomes were prepared by the solvent injection method (ether injection method) using a 1:1:1 ratio of lecithin/cholesterol/SRF in the mixture. Characterization of the prepared saponinosomes was performed by FTIR, dynamic light scattering (DLS), field-emission scanning electron microscopy (FE-SEM), and atomic force microscopy (AFM) analyses. In addition, a UV-vis spectrophotometer was used to determine the entrapment efficiency (EE) and in vitro release of the SRF. Finally, cell cytotoxicity of the different formulations was evaluated using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay on both mouse melanoma cells (B16F10) and fibroblasts (L929). Using DLS, AFM, and FE-SEM analyses, the particle size was determined to be 58 ± 6 nm with a zeta potential of -32 ± 2 mV. The calculated EE was 85 ± 3%. The results of the in vitro release profile showed that 68.2% of the SRF was released from the saponinosome after 48 h. The results of the MTT assay showed that the SRF and saponinosomes have high toxicity on B16F10 melanoma cells, but saponinosomes showed a significant decrease in cytotoxicity on L929 fibroblast cells compared with that of the SRF. Our results indicate that the SRF from Z. spina-christi has anticancer activity, and the saponinosomes prepared in this work can control tumor growth, improve therapeutic efficacy, and reduce the side effects of saponins.