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Planta Med 2020; 86(08): 538-547
DOI: 10.1055/a-1134-3378
Formulation and Delivery Systems of Natural Products
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Isoliquiritigenin Nanosuspension Enhances Cytostatic Effects in A549 Lung Cancer Cells

Fangxia Qiao‡
1   Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, Yinchuan, PR China
,
Yue Zhao‡
1   Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, Yinchuan, PR China
,
Yaping Mai
1   Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, Yinchuan, PR China
,
Jueshuo Guo
1   Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, Yinchuan, PR China
,
Luning Dong
1   Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, Yinchuan, PR China
,
Wannian Zhang
1   Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, Yinchuan, PR China
2   School of Pharmacy, Second Military Medical University Shanghai, Shanghai, PR China
,
Jianhong Yang
1   Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, Yinchuan, PR China
› Author Affiliations
Supported by: Ningxia International Cooperation Key Project 2018BFH02001 Supported by: Colleges and Universities in Ningxia S201910752016
Further Information

Publication History

received 07 November 2019
revised 15 February 2020

accepted 29 February 2020

Publication Date:
15 April 2020 (online)

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Abstract

Isoliquiritigenin, a flavonoid extracted from licorice root, has been shown to be active against most cancer cells; however, its antitumor activity is limited by its poor water solubility. The aim of this study was to develop a stable isoliquiritigenin nanosuspension for enhanced solubility and to evaluate its in vitro cytostatic activity in A549 cells. The nanosuspension of isoliquiritigenin was prepared through wet media milling with HPC SSL (hydroxypropyl cellulose-SSL) and PVP K30 (polyinylpyrrolidone-K30) as stabilizers, and the samples were then characterized according to particle size, zeta-potential, SEM (scanning electron microscopy), TEM (transmission electron microscopy), DSC (differential scanning calorimetry), XRPD (X-ray powder diffraction), FTIR (Fourier transform infrared spectroscopy), XPS (X-ray photoelectron spectroscopy), and in vitro release. The isoliquiritigenin nanosuspension prepared with HPC SSL and PVP K30 had particle sizes of 238.1 ± 4.9 nm and 354.1 ± 9.1 nm, respectively. Both nanosuspensions showed a surface charge of approximately − 20 mV and a lamelliform or ellipse shape. The dissolution of isoliquiritigenin from the 2 nanosuspensions was markedly higher than that of free isoliquiritigenin. In vitro studies on A549 cells indicated that the cytotoxicity and cellular uptake significantly improved after treatment with both nanosuspensions in comparison to the isoliquiritigenin solution. Furthermore, cell apoptosis analysis showed a 7.5 – 10-fold increase in the apoptosis rate induced by both nanosuspensions compared with pure drug. However, the cytotoxicity of pure drug and nanosuspension on normal cells (HELF) was lower, which indicated both isoliquiritigenin nanosuspensions have low toxicity to normal cells. Therefore, the isoliquiritigenin nanosuspension prepared with HPC SSL and PVP K30 as stabilizers may be a promising approach to improve the solubility and cytostatic activity of isoliquiritigenin.

Key words

isoliquiritigenin - nanosuspension - dissolution - lung cancer cells - cytotoxicity

Supporting Information

    The image of particle size, PDI, and zeta-potential of isoliquiritigenin nanosuspension, TEM images of isoliquiritigenin nanosuspension, DSC thermograms of materials, physical mixture (PM) and freeze-dried nanosuspensions, FTIR spectra of raw materials, PM and freeze-dried nanosuspensions, the cytotoxicity of the isoliquiritigenin solution and isoliquiritigenin nanosuspension against HELF cells, and the flow cytometric data used in the optimization study are provided as Supporting Information.

  • Supporting Information
 

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