Preparation and characterization of monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) micelles for the solubilization and in vivo delivery of luteolin.
Preparation and characterization of monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) micelles for the solubilization and in vivo delivery of luteolin.
复制标题
DOI：
10.2147/ijn.s45062
复制
发表时间：
2013
影响因子：
8
通讯作者：
Huang MJ
中科院分区：
文献类型：
--
作者：
Qiu JF;Gao X;Wang BL;Wei XW;Gou ML;Men K;Liu XY;Guo G;Qian ZY;Huang MJ
木犀草素是具有抗癌活性的黄酮类化合物之一，但其水溶性差限制了其在临床上的应用。在这项工作中，我们使用单甲氧基聚（乙二醇）-聚（e-己内酯）（MPEG-PCL）胶束通过自组装方法封装Lu，产生水溶性Lu/MPEG-PCL胶束。这些胶束的平均粒径为38.6 ± 0.6 nm（多分散指数= 0.16 ± 0.02），包封率为98.32% ± 1.12%，载药量为3.93% ± 0.25%。Lu/MPEG-PCL胶束可在体外缓慢释放Lu。Lu在MPEG-PCL胶束中的包封提高了半衰期（t½; 152.25 ± 49.92 vs [vs] 7.16 ± 1.23分钟，P = 0.007），曲线下面积（0-t）（2914.05 ± 445.17 vs 502.65 ± 140.12 mg/L/min，P = 0.001），曲线下面积（0-∞）（2989.03 ± 433.22 vs 503.81 ± 141.41 mg/L/min，P = 0.001）和峰值浓度大鼠静脉注射30 mg/kg的Lu后，其血药浓度分别为（92.70 ± 11.61）mg/L和（38.98 ± 7.73）mg/L，P = 0.003。Lu/MPEG-PCL胶束在体外对4 T1乳腺癌细胞（IC 50 = 6.4 ± 2.30 μg/mL）和C-26结肠癌细胞（IC 50 = 12.62 ± 2.17 μg/mL）的细胞毒作用仍保持不变。这些数据表明，将Lu包封到MPEG-PCL胶束中产生了具有潜在抗癌作用的Lu的水性制剂。
Luteolin (Lu) is one of the flavonoids with anticancer activity, but its poor water solubility limits its use clinically. In this work, we used monomethoxy poly(ethylene glycol)-poly(e-caprolactone) (MPEG-PCL) micelles to encapsulate Lu by a self-assembly method, creating a water-soluble Lu/MPEG-PCL micelle. These micelles had a mean particle size of 38.6 ± 0.6 nm (polydispersity index = 0.16 ± 0.02), encapsulation efficiency of 98.32% ± 1.12%, and drug loading of 3.93% ± 0.25%. Lu/MPEG-PCL micelles could slowly release Lu in vitro. Encapsulation of Lu in MPEG-PCL micelles improved the half-life (t½; 152.25 ± 49.92 versus [vs] 7.16 ± 1.23 minutes, P = 0.007), area under the curve (0-t) (2914.05 ± 445.17 vs 502.65 ± 140.12 mg/L/minute, P = 0.001), area under the curve (0–∞) (2989.03 ± 433.22 vs 503.81 ± 141.41 mg/L/minute, P = 0.001), and peak concentration (92.70 ± 11.61 vs 38.98 ± 7.73 mg/L, P = 0.003) of Lu when the drug was intravenously administered at a dose of 30 mg/kg in rats. Also, Lu/MPEG-PCL micelles maintained the cytotoxicity of Lu on 4T1 breast cancer cells (IC50 = 6.4 ± 2.30 μg/mL) and C-26 colon carcinoma cells (IC50 = 12.62 ± 2.17 μg/mL) in vitro. These data suggested that encapsulation of Lu into MPEG-PCL micelles created an aqueous formulation of Lu with potential anticancer effect.