Abstract
Curcumin (Curc) and its derivatives have been extensively used as natural adjuvants in different pathologies including cancer, cardiovascular disease, Alzheimer’s disease, etc. Nowadays research is focused on formulations based on Curc to improve pharmacokinetics, bioavailability, overcoming its low water solubility and instability. Within our ongoing research on nanooncologicals based on amphiphilic cyclodextrins (aCD), here we propose nanoassemblies based on non-ionic aCD (SC6OH) entrapping Curc (SC6OH/Curc) as nanocomplex adjuvant in anticancer therapy. Nanoassemblies were prepared, at maxima entrapment efficiency, in aqueous dispersion at Curc/SC6OH 2:1 M ratio (up to [Curc] = 200 µM that is 0.073 mg/mL) by solvent evaporation method and characterized by complementary spectroscopic techniques, by studying stability and release kinetic. Theoretical studies based on Molecular Mechanics (MM) and Molecular Dynamics (MD) methods were performed to understand at atomistic level the formation of SC6OH/Curc nanoassemblies, the stability and the dispersibility of the Curc within the aggregates. Finally, SC6OH/Curc was tested in five different cancer cell lines (A2780, A549, MDA-MB-231, MDA-MB-453 and HepG2) showing similar IC50 values vs free Curc dissolved in DMSO. All these results open the routes to the development of new highly water dispersible nanodrugs based on cyclodextrin and curcuminoids for controlled drug delivery.
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