Inhalable resveratrol-cyclodextrin complex loaded biodegradable nanoparticles for enhanced efficacy against non-small cell lung cancer.

Resveratrol (RES), a natural polyphenol in fruits, has shown promising anti-cancer properties. Due to its relative low toxicity which limits the adverse effects observed for conventional chemotherapeutics, RES has been proposed as an alternative. However, the therapeutic applications of RES have been limited due to low water solubility, as well as chemical and physical instability. This study investigated enhancing the anti-cancer activity of RES against non-small-cell-lung-cancer (NSCLC) by complexing with sulfobutylether-β-cyclodextrin (CD-RES) and loading onto polymeric nanoparticles (NPs). The physicochemical properties of the CD-RES NPs were then characterized. The CD-RES inclusion complex increased the water solubility of RES by ~66-fold. CD-RES NPs demonstrated very good aerosolization potential with a mass median aerodynamic diameter of 2.20 μm. Cell-based studies demonstrated improved therapeutic efficacy of CD-RES NPs compared to RES. This included enhanced cellular uptake, cytotoxicity, and apoptosis, while retaining antioxidant activity. The 3D spheroid study indicated an intensified anti-cancer effect of CD-RES NPs. Altogether, these findings marked CD-RES NPs as a potential inhalable delivery system of RES for the treatment NSCLC. Unlabelled Image • CD-RES inclusion complex was prepared to improve the aqueous solubility of RES by 66-folds. • CD-RES NPs proved to have excellent aerosolization potential using the Next-Generation Impactor™. • CD-RES loaded onto PLGA NPs significantly enhanced the anti-cancer effects when tested on NSCLC cell lines. • 3D spheroid study also indicated a considerably intensified anti-cancer effect of the CD-RES NPs compared to the plain drug. [ABSTRACT FROM AUTHOR]