Micelles Based on Methoxy Poly(Ethylene Glycol)-Cholesterol Conjugate for Controlled and Targeted Drug Delivery of a Poorly Water Soluble Drug
Micelles Based on Methoxy Poly(Ethylene Glycol)-Cholesterol Conjugate for Controlled and Targeted Drug Delivery of a Poorly Water Soluble Drug
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基于甲氧基聚乙二醇-胆固醇缀合物的胶束用于水溶性差的药物的受控和靶向药物输送
DOI：
10.1166/jbn.2012.1433
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发表时间：
2012-10-01
影响因子：
2.9
通讯作者：
Song, Xiangrong
中科院分区：
文献类型：
--
作者：
Li, Junming;He, Zhiyao;Song, Xiangrong
本研究将具有癌症化学预防作用和抗癌潜力的槲皮素(QC)负载到甲氧基聚乙二醇-胆固醇结合物(mpeg-chol)的聚合物胶束中，以增加其水溶性。首先通过两步酯化反应对胆固醇进行化学修饰，合成了临界胶束浓度(CMC)较低(4.0×10~(-7)M与13×10~(-7)M)的mpeg-Chol，然后通过自组装方法将QC引入mpeg-Chol胶束中。优化工艺参数后，QC胶束具有较高的载药量(3.66%)、包封率(93.51%)和纳米粒径(116 Nm)。DSC分析表明，QC以非共价形式存在于胶束中，以非晶态或固溶体形式存在于聚合物基质中。以添加1%(w/v)甘露醇作为冻干保护剂的冻干制剂可用于QC胶束的长期保存。与游离QC相比，QC胶束释放QC的速度更慢。此外，在pH为5的PBS中，QC从胶束中的释放速度略快于在pH为7.4时的PBS中，这表明QC胶束可能是pH敏感的，从而选择性地将QC输送到肿瘤组织中，而没有任何副作用。因此，mpeg-Chol是一种很有前途的胶束载体，可用于控制和靶向QC的肿瘤给药，QC胶束也值得进一步研究，作为一种潜在的癌症化学预防和治疗方案。
In this study, quercetin (QC) with cancer chemoprevention effect and anticancer potential was loaded into polymeric micelles of methoxy poly(ethylene glycol)-cholesterol conjugate (mPEG-Chol) in order to increase its water solubility. MPEG-Chol with lower critical micelle concentration (CMC) value (4.0 x 10(-7) M similar to 13 x 10(-7) M) was firstly synthesized involving two steps of chemical modification on cholesterol by esterification, and then QC was incorporated into mPEG-Chol micelles by self-assembly method. After the process parameters were optimized, QC-loaded micelles had higher drug loading (3.66%) and entrapment efficiency (93.51%) and nano-sized diameter (116 nm). DSC analysis demonstrated that QC had been incorporated non-covalently into the micelles and existed as an amorphous state or a solid solution in the polymeric matrix. The freeze-dried formulation with addition of 1% (w/v) mannitol as cryoprotectant was successfully developed for the long-term storage of QC-loaded micelles. Compared to free QC, QC-loaded micelles could release QC more slowly. Moreover, the release of QC from micelles was slightly faster in PBS at pH 5 than that in PBS at pH 7.4, which implied that QC-loaded micelles might be pH-sensitive and thereby selectively deliver QC to tumor tissue with unwanted side effects. Therefore, mPEG-Chol was a promising micellar vector for the controlled and targeted drug delivery of QC to tumor and QC-loaded micelles were also worth being further investigated as a potential formulation for cancer chemoprevention and treatment.