Resveratrol loaded functionalized nanostructured lipid carriers for breast cancer targeting: Systematic development, characterization and pharmacokinetic evaluation

Resveratrol (RSV) has shown to possess anti-cancer potential in various studies; however, its poor water solubility, extensive first-pass metabolism, and photostability issues have limited its clinical application. Therefore, the aim of the current investigation was to formulate and optimize a nanostructured lipid carriers (NLCs) based parenteral formulation of RSV for its effective delivery to breast cancer cells. NLCs loaded with RSV (RSV-NLCs) were formulated by the modified solvent injection technique and were systematically optimized using a three level-three factor Box-Behnken design. The optimized RSV-NLCs exhibited an optimum particle size of 88.3 +/- 3.1 nm and high entrapment efficiency of 88.0 +/- 2.6%. These optimized NLCs were further investigated for the targeting potential using folic acid as the targeting moiety and cell cytotoxicity experiments revealed high cytotoxic effects of folate modified NLCs (RSV-FA-NLCs) compared to unmodified NLCs on MCF-7 cells with high levels of over-expressed folate receptors suggesting the high potential of targeted NLCs in enhancing the therapeutic concentration of RSV to breast cancer cells. In vivo pharmacokinetic studies demonstrated a nine-fold increase in AUC values obtained with RSV-FA-NLCs (57.92 +/- 4.15 mu g h/mLh) in comparison to free RSV (6.37 +/- 1.16 mu g h/mLh). The promising results from this investigation corroborated the tremendous potential of lipidic nanocarriers in augmenting the therapeutic potential of RSV.