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 μM) was enhanced through the physical mixing with [WR]5 by 5.7 folds compared to that of curcumin alone in human leukemia (CCRFCEM) 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 ∼13% through the physical mixture and the conjugate, respectively, in CCRF-CEM cells after 72 h.
Amir Nasrolahi
AN
Shirazi
Naglaa Salem
NS
El-Sayed
Rakesh Kumar
RK
Tiwari
Kathy
K
Tavakoli
9401 Jeronimo Road, Chapman University, School of Pharmacy, Irvine, CA 92618, USA. parang@chapman.edu.
Keykavous
K
Parang
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D010456:Peptides, Cyclic / Q000008:administration & dosage* / Q000737:chemistry
D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; D003474:Curcumin