Abstract
Curcumin and resveratrol are naturally occurring polyphenolic compounds having anti-cancer potential. However, their poor aqueous solubility and bioavailability limits their clinical use. Entrapment of hydrophobic drugs into hydrophilic nanoparticles such as calcium alginate presents a means to deliver these drugs to their target site.|Curcumin and resveratrol loaded calcium alginate nanoparticles were prepared by emulsification and cross-linking process. The nanoparticles were characterized for particle size, zeta potential, moisture content, physical state of the drugs, physical stability, and entrapment efficiency. An UPLC method was developed and validated for the simultaneous analysis of curcumin and resveratrol. The in vitro release of drugs from the nanoparticles was studied using the dialysis membrane. The cytotoxicity and cellular uptake of the formulation was studied in DU145 prostate cancer cell line.|The particle size of the nanosuspension and freeze dried nanoparticles was found to be 12.53±1.06 nm and 60.23±15 nm, respectively. The zeta potential of blank as well as drug loaded nanoparticles were in the range of -13 to -25 mV. The moisture content of blank and drug loaded nanoparticles was 5.9±0.8% and 4.8±0.2%, respectively, as determined by Karl Fisher titrimetry. Both DSC and powder XRD studies indicated that curcumin as well as resveratrol were present in a non-crystalline state, in the nanoparticles. The entrapment efficiency for curcumin and resveratrol was found to be 49.3±4.3% and 70.99±6.1%, respectively. Resveratrol showed a higher release than curcumin (87.6±7.9% versus 16.3±3.1%) in 24 hours. Curcumin was found to be taken up by the cells from solution as well as the nanoparticles. Resveratrol had a poor cellular uptake. The drug loaded nanoparticles were found to exhibit cytotoxic effects on DU145 cells with a 47.2±7.7% cell survival, 72-hours post-treatment. Drug solution exhibited greater toxicity than nanoparticles at the highest concentrations. The formulation was found to be safe for intravenous administration. This formulation needs further testing for its efficacy in other cells lines such as prostate cancer, breast cancer and pancreatic cancer cell lines. The possible efflux mechanism for resveratrol transport in these cell needs future investigation.