Ouahab Ammar, Shao Chengyi, Shen Yan, Tu Jiasheng
Department of Pharmaceutics, China Pharmaceutical University , Nanjing , China and.
Drug Dev Ind Pharm. 2014 Jul;40(7):860-8. doi: 10.3109/03639045.2013.788017. Epub 2013 Apr 19.
Double loaded micelles (DLM) in which paclitaxel (PTX) and docetaxel (DTX) were co-solubilized with monomethoxy poly(ethylene glycol)-block-poly(d,l-lactide) (mPEG-PLA) copolymer were prepared and evaluated in an aim to investigate the effect of a combination of PTX and DTX on the stability of mPEG-PLA micelles compared to single drug-loaded micelles (SDM), especially that recent clinical anticancer formulations are limited by the existence of toxic excipients and stability issues.
The SDM and DLM of PTX and DTX were prepared by a solvent evaporation method. Micellar size, size distribution, drug loading content and drug release were investigated. Transmission electron microscopy was used to investigate the stabilization mechanism.
The drug loading efficiency of both PTX and DTX in DLM and SDM were 25% and 10%, respectively. (1)H NMR showed a successful encapsulation of both drugs in the polymeric micelle. DLM showed better physical stability at drug concentrations higher than 1 mg/mL compared to SDM. Moreover, DLM, SDM-PTX and SDM-DTX were stable for 24, 9 and 1 h, respectively. The stabilization mechanism of DLM was investigated, a network structure of DLM was observed in TEM graphs. Furthermore, DLM showed complete and faster drug release compared to SDM. mPEG-PLA double loaded micelles can deliver two poorly water soluble anticancer drugs at clinically relevant doses. The obtained results offer a promising alternative for double drug therapy without any formulation associated undesirable effects and encourage further in vivo development and optimization of the DLM as a drug delivery system for anticancer drugs.
制备了紫杉醇（PTX）和多西他赛（DTX）与单甲氧基聚（乙二醇）-嵌段-聚（d，l-丙交酯）（mPEG-PLA）共聚物共增溶的双载药胶束（DLM）并进行评估，旨在研究PTX和DTX联合使用对mPEG-PLA胶束稳定性的影响，与单载药胶束（SDM）相比，特别是因为近期临床抗癌制剂受到有毒辅料的存在和稳定性问题的限制。
采用溶剂蒸发法制备PTX和DTX的SDM和DLM。研究了胶束大小、大小分布、载药量和药物释放情况。使用透射电子显微镜研究稳定机制。
PTX和DTX在DLM和SDM中的载药效率分别为25%和10%。核磁共振氢谱显示两种药物均成功包封在聚合物胶束中。与SDM相比，DLM在药物浓度高于1mg/mL时表现出更好的物理稳定性。此外，DLM、SDM-PTX和SDM-DTX分别稳定24、9和1小时。研究了DLM的稳定机制，在透射电子显微镜图像中观察到DLM的网络结构。此外，与SDM相比，DLM显示出完全且更快的药物释放。mPEG-PLA双载药胶束可以以临床相关剂量递送两种难溶性抗癌药物。所获得的结果为双药治疗提供了一种有前景的替代方案，且没有任何制剂相关的不良影响，并鼓励进一步在体内开发和优化DLM作为抗癌药物的给药系统。
