Abstract
Curcumin and resveratrol are two natural products with activity against various types of cancers. However, they have poor bioavailability due to poor solubility, limiting their clinical applications. Solid lipid nanoparticles (SLNs) of these drugs present a means to improve their delivery to the target site.|Polymers such as 2-hydroxypropyl β-cyclodextrin (HPβCD), hydroxypropyl methyl cellulose (HPMC), polyvinylpyrrolidone (PVP), and eudragit EPO® (EPO) were screened using X-ray diffraction (XRD) for miscibility and proton nuclear magnetic resonance spectroscopy (1H-NMR) and infrared spectroscopy (IR) were used to study molecular interactions with the aim of selecting most suitable polymer for designing curcumin-resveratrol SLN. Curcumin-resveratrol along with the selected polymer were incorporated in various lipids to form emulsion which were probe sonicated and freeze-dried to obtain SLNs. SLNs were optimized for particle size range below 200 nm and were characterized by zeta potential, XRD, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), physical stability, and entrapment efficiency. A UV-visible method was developed and validated for the simultaneous analysis of curcumin and resveratrol. The in vitro release of drugs from the SLNs was studied using the direct dispersion method. The SLNs were tested for in vitro efficacy using colorectal cancer cell line.|HPβCD was found to have good miscibility with curcumin and resveratrol. It also showed hydrogen bonding tendency with both the drugs. Curcumin-resveratrol-gelucire 50/13-HPβCD and curcumin-resveratrol-gelucire 50/13 SLNs showed a particle size from 100-150 nm. SLNs were characterized by XRD, TGA, DSC. XRD results showed that the drugs were not in crystalline state; MDSC did not show melting endotherm of curcumin, thus complementing the XRD results; TGA showed no weight loss and SEM showed curcumin-resveratrol-gelucire 50/13 SLNs were spherical in shape. Curcumin-resveratrol-gelucire 50/13 SLNs were stable for 21 days with respect to particle size and zeta potential. Encapsulation of the drugs was in the range of 75-85% for both the SLNs. MTT assay indicated better IC50 value for curcumin-resveratrol-gelucire 50/13 as compared to curcumin-resveratrol-gelucire 50/13-HPβCD.|Novel SLNs of curcumin and resveratrol incorporated in lipid and polymer for anticancer activity were prepared and characterized. MTT assay showed activity of the formulations against cancer.