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

Abstract

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.

p-Sulfonato-Calix[4]arene Micelles Stabilize a Povidone Iodine Solution: Supramolecular Interactions, Iodine Retention, and Bactericidal Activity

“…As previously described in the presence of phosphate buffer [ 12 ], the CMC of SC4OC6 results as significantly lower (0.05 mM) if compared to that in plain water (0.49 mM), as expected for amphiphilic molecules in the presence of salts [ 29 , 30 ]. Furthermore, the self-assembly process is less exothermic than in the buffer-free aqueous solutions [ 31 , 32 , 33 ].…”

“…The self-aggregation process of the amphiphilic SC4OC6 has already been studied in plain water and in buffered solution [ 12 , 23 ]. However, as the change in the ionic medium can induce a significant variation in the CMC value [ 24 , 25 , 26 , 27 ], the aggregation features of SC4OC6 were specifically determined at the experimental conditions employed in the present work (10 mM phosphate/citrate buffer, pH 6, hereinafter referred to as PCB).…”

“…The (small) favorable entropic contribution is due to desolvation of both the polymer chain and the micelle surface upon binding. This result suggests that the polymer interacts with the exterior surface of the micelles and such interactions cause the release of superficial water of hydration to the bulk solvent [ 12 , 38 , 39 ]. The favorable Δ H value is likely due to CH-π and electrostatic interactions between the calixarene hydrophilic heads and the PVPI backbone that advantageously balance the enthalpic cost for desolvation [ 40 , 41 ].…”

“…They possess a hydrophobic cavity able to host ions and neutral molecules and a remarkable synthetic versatility that allows for obtaining a very large number of derivatives for applications in different fields, including pharmaceutical and biomedical areas [ 9 , 10 ]. Among calixarene derivatives, p -sulfonato-calix[4]arenes have gained interest in drug discovery and drug delivery [ 11 , 12 ], including antimicrobial applications [ 13 , 14 ], due to their proved low cytotoxicity [ 15 ].…”

Quantitative Analysis of the Interactions of Metal Complexes and Amphiphilic Systems: Calorimetric, Spectroscopic and Theoretical Aspects

“…Quantitative characterization of the interactions between calixarene-based micelles and model drugs (antibiotics and anticancer agents) was also reported when analyzing data obtained by ITC measurements through a simplified model, which assumes the formation of a 1:1 species between the guest and the micellar aggregate [43,44]. The net heats of the reaction were analyzed by HypCal [45], software that allows for the simultaneous determination of the standard enthalpy and binding constant values, which has been specifically designed to treat data obtained from ITC instruments operating in the overfilled mode.…”