Characterization, in Vivo and in Vitro Evaluation of Solid Dispersion of Curcumin Containing d-α-Tocopheryl Polyethylene Glycol 1000 Succinate and Mannitol.
Characterization, in Vivo and in Vitro Evaluation of Solid Dispersion of Curcumin Containing d-α-Tocopheryl Polyethylene Glycol 1000 Succinate and Mannitol.
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DOI：
10.3390/molecules21101386
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发表时间：
2016-10-17
期刊：
影响因子：
--
通讯作者：
Choi MK
中科院分区：
文献类型：
--
作者：
Song IS;Cha JS;Choi MK
本研究的目的是制备姜黄素固体分散体制剂，以提高其溶解度、溶出速率和口服生物利用度。以d-α-生育酚聚乙二醇1000琥珀酸酯（TPGS）和甘露醇为原料，采用溶剂挥发法和冷冻干燥法制备姜黄素-TPGS-甘露醇固体分散体。与姜黄素粉末及姜黄素、TPGS和甘露醇的物理混合物相比，姜黄素固体分散体的溶解度和溶出速率显著提高。约90%的姜黄素释放的固体分散体制剂在10分钟内。口服给药后的制剂给大鼠，观察到较高的血浆浓度的姜黄素，与增加的最大血浆浓度（Cmax）和血浆浓度-时间曲线（AUC）下的86和65倍，分别与姜黄素粉末。固体分散体制剂有效地增加肠通透性并抑制P-gp功能。这些作用增加了姜黄素在MDA-MB-231乳腺癌细胞中的抗增殖作用。此外，与姜黄素粉末、固体分散体制剂及其物理混合物孵育2 h，通过抑制P-gp介导的紫杉醇外排，导致紫杉醇在P-gp过表达的LLC-PK 1-P-gp和MDA-MB-231细胞中的不同细胞毒性作用。总之，与姜黄素相比，姜黄素与TPGS和甘露醇的固体分散体制剂可能是通过增加溶解度、溶出速率、细胞渗透性和P-gp调节来提高姜黄素的口服生物利用度和功效的有前途的选择。
The aim of this study was to prepare a solid dispersion formulation of curcumin to enhance its solubility, dissolution rate, and oral bioavailability. The formulation was prepared with d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and mannitol using solvent evaporation and freeze-drying methods, which yielded a solid dispersion composed of curcumin, TPGS, and mannitol at a ratio of 1:10:15 (w/w/w). The solubility and dissolution rate of the curcumin solid dispersion markedly improved compared with those of curcumin powder and a physical mixture of curcumin, TPGS, and mannitol. About 90% of the curcumin was released from the solid dispersion formulation within 10 min. After administering the formulation orally to rats, higher plasma concentrations of curcumin were observed, with increases in the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of 86- and 65-fold, respectively, compared with those of curcumin powder. The solid dispersion formulation effectively increased intestinal permeability and inhibited P-gp function. These effects increased the anti-proliferative effect of curcumin in MDA-MB-231 breast cancer cells. Moreover, 2 h incubation with curcumin powder, solid dispersion formulation, and its physical mixture resulted in differential cytotoxic effect of paclitaxel in P-gp overexpressed LLC-PK1-P-gp and MDA-MB-231 cells through the inhibition of P-gp-mediated paclitaxel efflux. In conclusion, compared with curcumin, a solid dispersion formulation of curcumin with TPGS and mannitol could be a promising option for enhancing the oral bioavailability and efficacy of curcumin through increased solubility, dissolution rate, cell permeability, and P-gp modulation.
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