Department of Polymer Science and Engineering, College of Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
J Control Release. 2013 Jun 10;168(2):105-14. doi: 10.1016/j.jconrel.2013.02.022. Epub 2013 Mar 6.
The in vivo stability and tumor targetability of self-assembled polymeric nanoparticles are crucial for effective drug delivery. In this study, to develop biostable nanoparticles with high tumor targetability, poly(ethylene glycol)-conjugated hyaluronic acid nanoparticles (PEG-HANPs) were mineralized through controlled deposition of inorganic calcium and phosphate ions on the nanoparticular shell via a sequential addition method. The resulting nanoparticles (M-PEG-HANPs) had a smaller size (153.7±4.5nm) than bare PEG-HANPs (265.1±9.5nm), implying that mineralization allows the formation of compact nanoparticles. Interestingly, when the mineralized nanoparticles were exposed to acidic buffer conditions (<pH6.5), their sizes increased rapidly due to dissolution of the inorganic minerals. Doxorubicin (DOX), chosen as the model anticancer drug, was effectively encapsulated into the bare and mineralized nanoparticles. For bare PEG-HANPs, DOX was released in a sustained manner and its release rate was not dependent on the pH of the solution. On the other hand, DOX release from M-PEG-HANPs was pH-dependent: i.e. DOX was slowly released from nanoparticles under physiological condition (pH7.4), whereas its release rates were much higher at mildly acidic environments (<pH6.5). From in vivo biodistribution study, it was found that M-PEG-HANPs could reach the tumor site more effectively than bare PEG-HANPs. The antitumor efficacy of DOX-loaded nanoparticles was evaluated after systemic administration into the tumor-bearing mice. Of the samples tested, the most effective antitumor efficacy was observed for DOX-loaded M-PEG-HANPs. Overall, these results suggest that M-PEG-HANPs could be a promising carrier for an anticancer drug.
自组装聚合物纳米粒子的体内稳定性和肿瘤靶向性对于有效的药物传递至关重要。在这项研究中，为了开发具有高肿瘤靶向性的生物稳定纳米粒子，通过在纳米粒子壳上通过顺序添加方法用无机钙和磷酸盐离子进行控制沉积，使聚乙二醇-接枝透明质酸纳米粒子（PEG-HANPs）矿化。所得纳米粒子（M-PEG-HANPs）的粒径（153.7±4.5nm）小于裸 PEG-HANPs（265.1±9.5nm），这意味着矿化允许形成更紧凑的纳米粒子。有趣的是，当矿化纳米粒子暴露于酸性缓冲条件（<pH6.5）时，由于无机矿物质的溶解，其粒径迅速增加。阿霉素（DOX）被选为模型抗癌药物，被有效地包封到裸和矿化纳米粒子中。对于裸 PEG-HANPs，DOX 以持续的方式释放，并且其释放速率与溶液的 pH 值无关。另一方面，M-PEG-HANPs 中的 DOX 释放依赖于 pH：即在生理条件（pH7.4）下，纳米粒子中 DOX 的释放速度较慢，而在轻度酸性环境（<pH6.5）下，其释放速度要高得多。从体内生物分布研究中发现，M-PEG-HANPs 比裸 PEG-HANPs 更能有效地到达肿瘤部位。在荷瘤小鼠中进行全身给药后，评估了载 DOX 纳米粒子的抗肿瘤功效。在所测试的样品中，观察到载 DOX 的 M-PEG-HANPs 的抗肿瘤功效最有效。总体而言，这些结果表明 M-PEG-HANPs 可以成为抗癌药物的有前途的载体。
