Tima Singkome, Anuchapreeda Songyot, Ampasavate Chadarat, Berkland Cory, Okonogi Siriporn
Nanoscience and Nanotechnology Program, The Graduate School, Chiang Mai University, Chiang Mai 50200, Thailand.
Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
Eur J Pharm Biopharm. 2017 May;114:57-68. doi: 10.1016/j.ejpb.2016.12.032. Epub 2017 Jan 12.
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.
本研究旨在开发一种稳定的姜黄素（CM）聚合物胶束制剂，以提高其溶解度和稳定性，并适用于白血病患者的临床应用。使用泊洛沙姆制备了载有CM的聚合物胶束（CM-胶束）。聚合物的化学结构影响胶束性质。CM-胶束的最佳制剂，即CM-P407，是由泊洛沙姆407在药物与聚合物比例为1:30时获得的，并用pH 7.4的磷酸盐缓冲溶液复水。CM-P407表现出最小尺寸为30.3±1.3nm，最高包封率为88.4±4.1%。当在-80°C储存60天时，CM-P407对CM保持高度保护，且尺寸无显著变化。与二甲基亚砜中的CM溶液（CM-DMSO）相比，两种制剂中CM的动力学降解均遵循伪一级反应，但CM在CM-P407中的半衰期约比在CM-DMSO中长200倍。关于对过表达FLT3的EoL-1白血病细胞的活性，CM-P407显示出比CM-DMSO更高的细胞毒性。此外，CM-P407对白血病细胞的细胞内摄取比CM-DMSO高2-3倍。CM-P407的这些有前景的结果将在啮齿动物和白血病治疗的临床研究中进一步研究。
