Curcumin-loaded γ -cyclodextrin-grafted hyaluronic acid nanoassimblies: In vitro investigation of anti-proliferative, wound healing, and anti-inflammatory potential

Many drugs belong to a class of molecules that suffer low aqueous solubility and poor cellular uptake, which leads to a lack of therapeutic efficacy and unwanted side effects. Curcumin (CUR) has many potential therapeutic effects and has been proven to have anti-cancer, anti-inflammatory, and wound-healing abilities. This study aims to develop a CUR nanocarrier to enhance its physiochemical characteristics. First, Mono-6-deoxyl-6-ethylenediamino-γ-cyclodextrin (γCDEDA) was grafted to a high molecular weight hyaluronic acid (HA) polymer by carbodiimide cross-linking chemistry using various HA:γCDEDA ratios followed by loading CUR into HA-γCDEDA conjugate that enable the formation of self-assembled nanoparticles (HA-γCDEDA NPs and HA-γCDEDA-CUR NPs).The synthesized HA-γCDEDA NPs were characterized using 1H NMR spectroscopy, DLS measurements, thermogravimetry analysis) TGA), differential scanning calorimetry (DSC), transmission electron microscopy (Patra et al.), encapsulation efficiency (EE%), and release kinetics. Further, cellular uptake, anti-cancer activity, wound healing ability, and anti-inflammatory potential were investigated. The results showed successful conjugation of γCDEDA to HA polymer and spherical HA-γCDEDA and HA-γCDEDA-CUR self-assembled NPs with morphological changes observed upon CUR loading. Moreover, HA-γCDEDA NPs showed reasonable thermal and colloidal stability. The cellular uptake and anti-proliferative effect of HA-γCDEDA-CUR and γCDEDA-CUR NPs demonstrated higher uptake and cytotoxicity to breast cancer cell lines (MDA-MB-231 and MCF-7) compared to CURFree. Interestingly, HA-γCDEDA-CUR NPs showed a higher wound healing activity than γCDEDA-CUR NPs and CURFree in HDF cells. Moreover, the inflammatory response of THP-1 showed a reduction in the inflammatory-related genes IL-10, IL-1β, IL-6, IL-8, TNF-α, and IRAK-1 after activation by lipopolysaccharide LPS and exposure to HA-γCDEDA-CUR NPs, γCDEDA-CUR NPs, and CURFree treatments. In conclusion, HA-γCDEDA-CUR NPs can be a promising nanocarrier for CUR and other clinically potent hydrophobic molecules.