Enhanced Allicin Cytotoxicity on HEPG-2 Cells Using Glycyrrhetinic Acid Surface-Decorated Gelatin Nanoparticles

Abstract

The cytotoxic potential of allicin was evaluated on different cancer cell lines, particularly, hepatic (HepG-2), breast (MCF-7), lung (A-549), and prostatic (PC-3), where allicin scored an IC₅₀ score of 19.26 μM on HepG-2. In order to increase the cell uptake, optimized allicin-loaded gelatin nanoparticles (GNPs) were prepared where the optimum formulation was surface-conjugated to glycyrrhetinic acid. GNPs were optimized using a D-optimal design. The optimum formulation had a particle size of 370.7 ± 6.78 nm and polydispersity index of 0.0363 ± 0.009 and 39.13 ± 2.38% of drug entrapment. The conjugation of the ligand, glycyrrhetinic acid with allicin-loaded GNPs, was confirmed utilizing ¹H NMR. Drug release profiles in the presence/absence of collagenase were obtained. Finally, a cytotoxicity study on HepG-2 was performed for the unconjugated and conjugated allicin-loaded GNPs scoring IC₅₀ of 10.95 and 5.046 μM, revealing two- and fourfold enhancements in allicin cytotoxicity, respectively. To our knowledge, the ligand-carrier pair, glycyrrhetinic acid-gelatin, was not explored before, and the developed system poses a successful liver cancer therapy.

Figure 1

Evaluation of the cytotoxic potential of allicin on: (A) human hepatocellular cancer cell line HepG-2, (B) human breast cancer cell line MCF-7, (C) human lung cancer cell line, and (D) human prostatic cancer cell line.

Figure 2

TEM images for the prepared allicin-loaded GNPs at a magnification power of 50 000× for (A,C) and 25 000× for (B).

Figure 3

In vitro release profiles of allicin from the prepared GNPs in PBS of pH 7.4 with and without collagenase.

Figure 4

Cytotoxicity of unconjugated and conjugated allicin-loaded GNPs on HepG-2 cells.

Figure 5

Interaction of glycyrrhetinic acid with the ASGPR. Molecular docking displayed in (A) 2D and (B) 3D images.