Zhang Juan, Men Ke, Gu Yingchun, Wang Xiuhong, Gou Maling, Guo Gang, Luo Feng, Qian Zhiyong
State Key Laboratory of Biotherapy and Cancer Center West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
J Nanosci Nanotechnol. 2011 Jun;11(6):5054-61. doi: 10.1166/jnn.2011.4121.
Doxorubicin has been widely used in cancer treatment, but its severe side-effects restrict its clinical application greatly. So, we hope to design a novel delivery system to decrease its side-effects. In this paper, we prepared core cross-linked micelle based on poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (CCPCEC) at about 30 nm in diameter with a narrow distribution. The prepared core cross-linked PCL-PEG-PCL micelles were employed to load doxorubicin by pH-induced self-assembly method. Doxorubicin-loading did not obviously affect the micelle size or size distribution. Furthermore, these micelles exhibited a significantly enhanced thermodynamic stability against dilution with aqueous solvents and showed CMC in the range of 1 x 10(-3) to 2 x 10(-3) mg/mL. Cytotoxicity study confirmed great biocompatibility of the micelles and showed that the encapsulated doxorubicin in CCPCEC micelles enhanced the cytotoxicity of doxorubicin on C26 cell line in vitro. Moreover, in vitro release profile demonstrated a significant difference between rapid release of free doxorubicin and much slower and sustained release of doxorubicin-loaded core cross-linked micelles. In addition, a faster DOX-release from micelles at pH 5.5 than that at pH 7.4 was also observed. These results suggested that this new biodegradable Core Cross-linked PCL-PEG-PCL Micelles might be potential carriers for drug delivery in cancer chemotherapy.
阿霉素已广泛应用于癌症治疗,但其严重的副作用极大地限制了其临床应用。因此,我们希望设计一种新型给药系统以降低其副作用。在本文中,我们制备了基于聚(ε-己内酯)-聚(乙二醇)-聚(ε-己内酯)(CCPCEC)的核交联胶束,其直径约为30 nm,分布狭窄。通过pH诱导自组装方法,将制备的核交联聚己内酯-聚乙二醇-聚己内酯胶束用于负载阿霉素。负载阿霉素并未明显影响胶束的大小或尺寸分布。此外,这些胶束在用水性溶剂稀释时表现出显著增强的热力学稳定性,其临界胶束浓度在1×10⁻³至2×10⁻³mg/mL范围内。细胞毒性研究证实了胶束具有良好的生物相容性,并表明CCPCEC胶束中包封的阿霉素增强了阿霉素在体外对C26细胞系的细胞毒性。此外,体外释放曲线表明游离阿霉素的快速释放与负载阿霉素的核交联胶束的更缓慢且持续的释放之间存在显著差异。另外,还观察到胶束在pH 5.5时比在pH 7.4时阿霉素释放更快。这些结果表明,这种新型可生物降解的核交联聚己内酯-聚乙二醇-聚己内酯胶束可能是癌症化疗中药物递送的潜在载体。