title: Stable curcumin-loaded polymeric micellar formulation for enhancing cellular uptake and cytotoxicity to FLT3 overexpressing EoL-1 leukemic cells.
abstract: 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±1.3nm and highest entrapment efficiency of 88.4±4.1%. When stored at -80°C for 60days, 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.
authors.affiliation: Nanoscience and Nanotechnology Program, The Graduate School, Chiang Mai University, Chiang Mai 50200, Thailand.
authors.forename: Singkome
authors.initials: S
authors.lastname: Tima
authors.affiliation: Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
authors.forename: Songyot
authors.initials: S
authors.lastname: Anuchapreeda
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand.
authors.forename: Chadarat
authors.initials: C
authors.lastname: Ampasavate
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, University of Kansas, KS 66047, USA. Electronic address: berkland@ku.edu.
authors.forename: Cory
authors.initials: C
authors.lastname: Berkland
authors.affiliation: Nanoscience and Nanotechnology Program, The Graduate School, Chiang Mai University, Chiang Mai 50200, Thailand; Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand. Electronic address: siriporn.okonogi@cmu.ac.th.
authors.forename: Siriporn
authors.initials: S
authors.lastname: Okonogi
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000737:chemistry*; D004121:Dimethyl Sulfoxide; D004339:Drug Compounding; D006207:Half-Life; D006801:Humans; D008823:Micelles; D010316:Particle Size; D020442:Poloxamer; D011108:Polymers; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013501:Surface-Active Agents; D051941:fms-Like Tyrosine Kinase 3 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D008823:Micelles; D011108:Polymers; D013501:Surface-Active Agents; D020442:Poloxamer; D012710:Serum Albumin, Bovine; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3; D003474:Curcumin; D004121:Dimethyl Sulfoxide
keywords: Block copolymeric micelles; Cellular uptake; Curcumin; FLT3; Leukemia; Poloxamer 407; Stability