A Novel Curcumin Arginine Salt: A Solution for Poor Solubility and Potential Anticancer Activities

Abstract

Curcumin is a natural polyphenolic compound with well-known anticancer properties. Poor solubility and permeability hamper its use as an anticancer pharmaceutical product. In this study, L-arginine, a basic amino acid and a small hydrophilic molecule, was utilized to form a salt with the weak acid curcumin to enhance its solubility and potentiate the anticancer activities of curcumin. Two methods were adopted for the preparation of curcumin: L-arginine salt, namely, physical mixing and coprecipitation. The ion pair or salt was characterized for docking, solubility, DSC, FTIR, XRD, in vitro dissolution, and anticancer activities using MCF7 cell lines. The molecular docking suggested a salt/ion-pair complex between curcumin and L-arginine. Curcumin solubility was increased 335- and 440-fold by curcumin in L-arginine, physical, and co-precipitated mixtures, respectively. Thermal and spectral analyses supported the molecular docking and formation of a salt/ion pair between curcumin and L-arginine. The cytotoxicity of curcumin L-arginine salt significantly improved (p < 0.05) by 1.4-fold, as evidenced by the calculated IC50%, which was comparable to Taxol (the standard anticancer drug but with common side effects).

Keywords: L-arginine; breast cancer; curcumin; cytotoxicity.

Figure 1

Possible interactions between curcumin and L-arginine. Dashed lines denote H-bond length in Angstrom.

Figure 2

Solubility (A) and pH of the solutions measured at equilibrium for curcumin and curcumin–L-arginine physical (PM) and coprecipitated (Coppt) mixtures (B) (results are expressed as mean ± SD; n = 3).

Figure 3

DSC thermal spectra of curcumin, curcumin-L-arginine physical mixture, and coprecipitated dispersion.

Figure 4

FTIR spectra of curcumin, curcumin-L-arginine physical mixture, and coprecipitated dispersion.

Figure 5

XRD spectra of curcumin, curcumin-L-arginine physical mixture, and coprecipitated dispersion.

Figure 6

In vitro drug dissolution from curcumin alone, curcumin and L-arginine, and curcumin and L-arginine PM and Coppt (results are expressed as mean ± SD; n = 3).

Figure 7

Cytotoxicity (%) of six different concentrations of curcumin, curcumin and L-arginine salt, and paclitaxel (Taxol^®) using MCF-7 human breast epithelial cell lines (results are expressed as mean ± SD; n = 5).