Co-Loading of Temozolomide and Curcumin into a Calix[4]arene-Based Nanocontainer for Potential Combined Chemotherapy: Binding Features, Enhanced Drug Solubility and Stability in Aqueous Medium

The co-delivery of anticancer drugs into tumor cells by a nanocarrier may provide a new paradigm in chemotherapy. Temozolomide and curcumin are anticancer drugs with a synergistic effect in the treatment of multiform glioblastoma. In this study, the entrapment and co-entrapment of temozolomide and curcumin in a p-sulfonato-calix[4]arene nanoparticle was investigated by NMR spectroscopy, UV-vis spectrophotometry, isothermal titration calorimetry, and dynamic light scattering. Critical micellar concentration, nanoparticle size, zeta potential, drug loading percentage, and thermodynamic parameters were all consistent with a drug delivery system. Our data showed that temozolomide is hosted in the cavity of the calix[4]arene building blocks while curcumin is entrapped within the nanoparticle. Isothermal titration calorimetry evidenced that drug complexation and entrapment are entropy driven processes. The loading in the calixarene-based nanocontainer enhanced the solubility and half-life of both drugs, whose medicinal efficacy is affected by low solubility and rapid degradation. The calixarene-based nanocontainer appears to be a promising new candidate for nanocarrier-based drug combination therapy for glioblastoma.