Feng Chunsheng, Piao Meihua, Li Di
Department of Anesthesiology, The First Hospital of Jilin University, Changchun 130021, China.
Department of Chemistry, Northeast Normal University, Changchun 130024, China.
Polymers (Basel). 2016 Apr 22;8(4):165. doi: 10.3390/polym8040165.
The instability of PEGylated polylactide micelles is a challenge for drug delivery. Stereocomplex interaction between racemic polylactide chains with different configurations provides an effective strategy to enhance the stability of micelles as the nanocarriers of drugs. In this work, a stereocomplex micelle (SCM) self-assembled from the amphiphilic triblock copolymers comprising poly(ethylene glycol) (PEG), and dextrorotatory and levorotatory polylactides (PDLA and PLLA) was applied for efficient drug delivery. The spherical SCM showed the smallest scale and the lowest critical micelle concentration (CMC) than the micelles with single components attributed to the stereocomplex interaction between PDLA and PLLA. 10-Hydroxycamptothecin (HCPT) as a model antitumor drug was loaded into micelles. Compared with the loading micelles from individual PDLA and PLLA, the HCPT-loaded SCM exhibited the highest drug loading efficiency (DLE) and the slowest drug release in phosphate-buffered saline (PBS) at pH 7.4, indicating its enhanced stability in circulation. More fascinatingly, the laden SCM was demonstrated to have the highest cellular uptake of HCPT and suppress malignant cells most effectively in comparison to the HCPT-loaded micelles from single copolymer. In summary, the stereocomplex-enhanced PLA⁻PEG⁻PLA micelle may be promising for optimized drug delivery in the clinic.
聚乙二醇化聚丙交酯胶束的不稳定性是药物递送面临的一项挑战。具有不同构型的外消旋聚丙交酯链之间的立体络合相互作用提供了一种有效的策略，可增强作为药物纳米载体的胶束的稳定性。在本研究中，一种由包含聚乙二醇（PEG）、右旋聚丙交酯和左旋聚丙交酯（PDLA和PLLA）的两亲性三嵌段共聚物自组装而成的立体络合胶束（SCM）被用于高效药物递送。由于PDLA和PLLA之间的立体络合相互作用，球形SCM比单一组分的胶束尺寸最小且临界胶束浓度（CMC）最低。将10-羟基喜树碱（HCPT）作为模型抗肿瘤药物载入胶束中。与由单个PDLA和PLLA制成的载药胶束相比，载有HCPT的SCM在pH 7.4的磷酸盐缓冲盐水（PBS）中表现出最高的载药效率（DLE）和最慢的药物释放，表明其在循环中的稳定性增强。更令人感兴趣的是，与由单一共聚物制成的载有HCPT的胶束相比，载药SCM被证明对HCPT具有最高的细胞摄取率，并能最有效地抑制恶性细胞。总之，立体络合增强的PLA⁻PEG⁻PLA胶束在临床优化药物递送方面可能具有广阔前景。
