Peganum harmala Alkaloids Self-Assembled Supramolecular Nanocapsules with Enhanced Antioxidant and Cytotoxic Activities

Amphiphilic macrocycles, such as p-sulfonatocalix[6]arenes (p-SC6), have demonstrated great potential in designing synthetic nanovesicles based on self-assembly approaches. These supramolecular nanovesicles are capable of improving the solubility, stability, and biological activity of various drugs. In the present study, the biologically active harmala alkaloid-rich fraction (HARF) was extracted from Peganum harmala L. seeds. Ultraperformance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC/ESI-MS) analysis of HARF revealed 15 alkaloids. The reversed-phase high-performance liquid chromatography (RP-HPLC) analysis revealed three peaks: peganine, harmol, and harmine. The HARF was then encapsulated in p-SC6 nanocapsules employing a thin-film hydration approach. The designed nanocapsules had an average particle size of 264.8 +/- 10.6 nm, and a surface charge of -30.3 +/- 2.2 mV. They were able to encapsulate 89.3 +/- 1.4, 74.4 +/- 1.3, and 76.1 +/- 1.7% of the three harmala alkaloids; harmine, harmol, and peganine; respectively. The in vitro drug release experiments showed the potential of the designed nanocapsules to release their cargo at a pH of 5.5 (typical of cancerous tissue). The IC so values of HARF encapsulated in p-SC6 (H/p-SC6 nanocapsules) were 5 and 2.7 mu g/mL against ovarian cancer cells (SKOV-3) and breast adenocarcinoma cells (MCF-7), respectively. The prepared nanocapsules were found to be biocompatible when tested on human skin fibroblasts. Additionally, the antioxidant activity of the designed nanocapsules was 5 times that of the free powder fraction; the IC50 of the H/p-SC6 nanocapsules was 30.1 +/- 1.3 mu g/mL, and that of the HARF was 169.3 +/- 7.2 mu g/mL. In conclusion, encapsulation of P. harmala alkaloid-rich fraction into self-assembled p-SC6 significantly increases its antioxidant and cytotoxic activities.

Automated summary

Amphiphilic macrocycles like p-sulfonatocalix[6]arenes have shown potential in designing synthetic nanovesicles. These nanovesicles can improve drug solubility, stability, and biological activity. Encapsulation of harmala alkaloid-rich fraction (HARF) in p-SC6 nanocapsules significantly increased antioxidant and cytotoxic activities.