State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, People's Republic of China.
Biomed Mater. 2010 Dec;5(6):065006. doi: 10.1088/1748-6041/5/6/065006. Epub 2010 Oct 22.
Honokiol, an active principle extracted from Magnolia officinalis, has great potential as a cancer treatment. However, its poor water solubility greatly hampers its delivery to the tumor sites at an effective concentration. In this study, an amphiphilic polymer-drug conjugate was successfully prepared by condensation of low molecular weight monomethoxy-poly(ethylene glycol) (MPEG)-2000 with honokiol (HK) through an ester linkage to increase the hydrophilicity of honokiol. The MPEG-honokiol (MPEG-HK) conjugate prepared formed nano-sized micelles, with a mean particle size of less than 20 nm (MPEG-HK, 360 µg ml(-1)) in water, which could be well dispersed in water. The nanoparticles obtained were characterized by particle size distribution, morphology and zeta potential. The stability and hydrolysis profile of the polymeric pro-drug in phosphate-buffered saline (PBS) and plasma were also studied and the results showed that only 20% of the conjugated honokiol was released in 2.0 h in beagle dog plasma, while in PBS the time required to reach 20% of honokiol release was >200 h. Meanwhile, the inhibitory activity of the honokiol conjugate was found to be retained in vitro against LL/2 cell lines with an IC50 value of 10.7 µg ml(-1). These results suggest that the polymer-drug conjugate provides a potential new approach to hydrophobic drugs, such as honokiol, in formulation design.
厚朴酚是从厚朴中提取的一种活性成分，具有很大的癌症治疗潜力。然而，其较差的水溶性极大地阻碍了它以有效浓度递送到肿瘤部位。在这项研究中，通过低分子量单甲氧基聚乙二醇（MPEG）-2000 与厚朴酚（HK）的缩合反应成功制备了一种两亲性聚合物-药物偶联物，通过酯键增加了厚朴酚的亲水性。所制备的 MPEG-厚朴酚（MPEG-HK）缀合物形成纳米级胶束，在水中的平均粒径小于 20nm（MPEG-HK，360μgml-1），可以很好地分散在水中。所得纳米粒通过粒径分布、形态和zeta 电位进行了表征。还研究了聚合物前药在磷酸盐缓冲盐水（PBS）和血浆中的稳定性和水解情况，结果表明，在犬血浆中，只有 20%的共轭厚朴酚在 2.0h 内释放，而在 PBS 中，达到 20%厚朴酚释放所需的时间>200h。同时，发现厚朴酚缀合物在体外对 LL/2 细胞系的抑制活性保持不变，IC50 值为 10.7μgml-1。这些结果表明，聚合物-药物偶联物为厚朴酚等疏水性药物的制剂设计提供了一种潜在的新方法。
