Cyclic Peptide Containing Hydrophobic and Positively Charged Residues as a Drug Delivery System for Curcumin

Due to the low water solubility and hydrophobic nature of curcumin, an efficient cellular uptake is critical for its biological activity. We have previously developed a number of homochiral L-cyclic peptides containing arginine and tryptophan as cell-penetrating peptides. Among the synthesized peptides, [WR](5) containing five arginine and five tryptophan residues was found to be the most efficient one. Here, we have compared the application of [WR] 5 to improve the intracellular uptake of curcumin by using both peptide-curcumin conjugate and physical mixture (peptide + curcumin) strategies. Flow cytometry results showed that the intracellular uptake of curcumin (50 mu M) was enhanced through the physical mixing with [WR](5) by 5.7 folds compared to that of curcumin alone in human leukemia (CCRF-CEM) cells after 3 h. When [WR](5) was conjugated with curcumin, the intracellular uptake was enhanced by 4 fold. These data suggest that the physical mixture can work more efficiently in enhancing the cellular delivery of curcumin. Furthermore, the antiproliferative activity of curcumin was enhanced by 20% and similar to 13% through the physical mixture and the conjugate, respectively, in CCRF-CEM cells after 72 h.