TY - JOUR
T1 - Cyclic peptide containing hydrophobic and positively charged residues as a drug delivery system for curcumin
AU - Shirazi, Amir Nasrolahi
AU - El-Sayed, Naglaa Salem
AU - Tiwari, Rakesh Kumar
AU - Tavakoli, Kathy
AU - Parang, Keykavous
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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.
AB - 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.
KW - Antiproliferative activity
KW - Curcumin
KW - Cyclic peptides
KW - Drug delivery systems
UR - http://www.scopus.com/inward/record.url?scp=84973616577&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84973616577&partnerID=8YFLogxK
M3 - Article
C2 - 26511089
AN - SCOPUS:84973616577
SN - 1567-2018
VL - 13
SP - 409
EP - 417
JO - Current Drug Delivery
JF - Current Drug Delivery
IS - 3
ER -