Fabrication of a ternary β-cyclodextrin/curcumin/methotrexate compound for drug co-delivery, cytotoxicity and cell phagocytosis

This study investigates the drug co-delivery, cytotoxicity and cell phagocytosis of the ternary compound of β-CD/CUR/MTX prepared via co-precipitation methods. Fourier-transform infrared spectroscopy (FTIR), powder X-ray diffraction (XRD), 1 H NMR and thermogravimetric analysis (TGA) confirmed the successful encapsulation of CUR and MTX. Scanning electron microscopy (SEM) revealed rock-like morphologies for β-CD, β-CD/MTX, and β-CD/CUR/MTX. While β-CD/CUR exhibited micro-scaled rod structures. Thermogravimetric analysis (TGA) indicated that the compound maintain stability up to 200°C, although the ternary β-CD/CUR/MTX demonstrated an initial mass loss at approximately 120°C. Molecular docking studies indicated a strong binding affinity of β-CD with both CUR and MTX driving by hydrogen bonding. DPPH radical scavenging assays demonstrated that the β-CD/CUR and β-CD/CUR/MTX exhibited enhanced water solubility and antioxidant capacities compared to β-CD and β-CD/MTX. In vitro release studies revealed β-CD/MTX displayed a controlled release behavior of MTX, achieving 80-95% within 120 minutes. Whereas CUR loaded β-CD/CUR compound exhibited a rapid release of approximately 50% within 20 minutes. The release profile of β-CD/CUR/MTX was significantly influenced by pH, in which the release at pH 5.3 was higher than that at pH 7.4, and exceeding 80% after 120 minutes. Importantly, the compounds (β-CD/CUR and β-CD/CUR/MTX) at a concentration of 80 μM had a significant inhibitory cell viability and phagocytosed behavior on HepG2.