TY - JOUR
T1 - Stable curcumin-loaded polymeric micellar formulation for enhancing cellular uptake and cytotoxicity to FLT3 overexpressing EoL-1 leukemic cells
AU - Tima, Singkome
AU - Anuchapreeda, Songyot
AU - Ampasavate, Chadarat
AU - Berkland, Cory
AU - Okonogi, Siriporn
N1 - Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - The present study aims to develop a stable polymeric micellar formulation of curcumin (CM) with improved solubility and stability, and that is suitable for clinical applications in leukemia patients. CM-loaded polymeric micelles (CM-micelles) were prepared using poloxamers. The chemical structure of the polymers influenced micellar properties. The best formulation of CM-micelles, namely CM-P407, was obtained from poloxamer 407 at drug to polymer ratio of 1:30 and rehydrated with phosphate buffer solution pH 7.4. CM-P407 exhibited the smallest size of 30.3 ± 1.3 nm and highest entrapment efficiency of 88.4 ± 4.1%. When stored at −80 °C for 60 days, CM-P407 retained high protection of CM and had no significant size change. In comparison with CM solution in dimethyl sulfoxide (CM-DMSO), CM kinetic degradation in both formulations followed a pseudo-first-order reaction, but the half-life of CM in CM-P407 was approx. 200 times longer than in CM-DMSO. Regarding the activity against FLT3 overexpressing EoL-1 leukemic cells, CM-P407 showed higher cytotoxicity than CM-DMSO. Moreover, intracellular uptake to leukemic cells of CM-P407 was 2–3 times greater than that of CM-DMSO. These promising results for CM-P407 will be further investigated in rodents and in clinical studies for leukemia treatment.
AB - The present study aims to develop a stable polymeric micellar formulation of curcumin (CM) with improved solubility and stability, and that is suitable for clinical applications in leukemia patients. CM-loaded polymeric micelles (CM-micelles) were prepared using poloxamers. The chemical structure of the polymers influenced micellar properties. The best formulation of CM-micelles, namely CM-P407, was obtained from poloxamer 407 at drug to polymer ratio of 1:30 and rehydrated with phosphate buffer solution pH 7.4. CM-P407 exhibited the smallest size of 30.3 ± 1.3 nm and highest entrapment efficiency of 88.4 ± 4.1%. When stored at −80 °C for 60 days, CM-P407 retained high protection of CM and had no significant size change. In comparison with CM solution in dimethyl sulfoxide (CM-DMSO), CM kinetic degradation in both formulations followed a pseudo-first-order reaction, but the half-life of CM in CM-P407 was approx. 200 times longer than in CM-DMSO. Regarding the activity against FLT3 overexpressing EoL-1 leukemic cells, CM-P407 showed higher cytotoxicity than CM-DMSO. Moreover, intracellular uptake to leukemic cells of CM-P407 was 2–3 times greater than that of CM-DMSO. These promising results for CM-P407 will be further investigated in rodents and in clinical studies for leukemia treatment.
KW - Block copolymeric micelles
KW - Cellular uptake
KW - Curcumin
KW - FLT3
KW - Leukemia
KW - Poloxamer 407
KW - Stability
UR - https://www.scopus.com/pages/publications/85009944213
U2 - 10.1016/j.ejpb.2016.12.032
DO - 10.1016/j.ejpb.2016.12.032
M3 - Article
C2 - 28089916
AN - SCOPUS:85009944213
SN - 0939-6411
VL - 114
SP - 57
EP - 68
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
ER -