Wu Wenqi, Chen Hui, Shan Fengying, Zhou Jing, Sun Xun, Zhang Ling, Gong Tao
Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University , 29 Wangjiang Rd, Chengdu, Sichuan 610041, People's Republic of China.
Mol Pharm. 2014 Oct 6;11(10):3378-85. doi: 10.1021/mp500019p. Epub 2014 Apr 25.
The purpose of this study was to develop a safe and effective drug delivery system for local chemotherapy. A novel injectable in-situ-forming gel system was prepared using small molecule materials, including phospholipids, medium chain triglycerides (MCTs), and ethanol. Thus, this new sustained release system was named PME (first letter of phospholipids, MCT, and ethanol). PME has a well-defined molecule structure, a high degree of safety, and better biocompatible characteristics. It was in sol state with low viscosity in vitro and turned into a solid or semisolid gel in situ after injection. When loaded with doxorubicin (Dox), PME-D (doxorubicin-loaded PME) exhibited notably antitumor efficiency in S180 sarcoma tumors bearing mice after a single intratumoral injection. In vitro, PME-D had remarkable antiproliferative efficacies against MCF-7 breast cancer cells for over 5 days. Moreover, the initial burst effect can hardly be observed from PME system, which was different from many other in-situ-forming gels. The in vivo biodistribution study showed the high Dox concentration in tumors compared with other major organs after PME-D intratumoral administration. The strong signal in tumors was retained for more than 14 days after one single injection. The high concentration of Dox in tumor and long-term retention may explain the superior therapeutic efficacy and reduced side effects. The PME-D in-situ-forming gel system is a promising drug delivery system for local chemotherapy.
本研究的目的是开发一种用于局部化疗的安全有效的药物递送系统。使用小分子材料制备了一种新型的可注射原位形成凝胶系统，这些材料包括磷脂、中链甘油三酯（MCTs）和乙醇。因此，这种新的缓释系统被命名为PME（磷脂、MCT和乙醇的首字母）。PME具有明确的分子结构、高度的安全性和更好的生物相容性特征。它在体外呈低粘度的溶胶状态，注射后在原位转变为固体或半固体凝胶。当负载阿霉素（Dox）时，PME-D（负载阿霉素的PME）在单次瘤内注射后对荷S180肉瘤的小鼠显示出显著的抗肿瘤效果。在体外，PME-D对MCF-7乳腺癌细胞具有超过5天的显著抗增殖效果。此外，从PME系统中几乎观察不到初始突释效应，这与许多其他原位形成凝胶不同。体内生物分布研究表明，PME-D瘤内给药后肿瘤中的阿霉素浓度高于其他主要器官。单次注射后，肿瘤中的强信号保留超过14天。肿瘤中阿霉素的高浓度和长期保留可能解释了其卓越的治疗效果和减少的副作用。PME-D原位形成凝胶系统是一种有前途的局部化疗药物递送系统。
