Department of Chemistry, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
Eur J Pharm Sci. 2011 Apr 18;42(5):517-26. doi: 10.1016/j.ejps.2011.02.006. Epub 2011 Feb 23.
A novel folate-decorated maleilated pullulan-doxorubicin conjugate (abbreviated as FA-MP-DOX) for active tumor targeting was set up. The structure of this conjugate was confirmed by (1)H NMR analysis. Furthermore, the conjugation efficiency, drug release property and stability of the conjugate were determined. The cellular uptake and cytotoxicity were assessed by using ovarian carcinoma A2780 cells as in vitro cell model. In vitro DOX release from FA-MP-DOX conjugate occurred at a faster rate at acidic pH compared to neutral pH (7.4). After 30 h of incubation at pH 2.5, 5.0 and 7.4 the released free DOX was about 68.71%, 50.08% and 26%, respectively. Based on the IC(50) values, the conjugate was found more effective with ovarian carcinoma A2780 cells than the parent drug after 48 h culture. These results suggested that FA-MP-DOX conjugate could be a promising doxorubicin carrier for its targeted and intracellular delivery.
一种新型叶酸修饰的马来化普鲁兰-阿霉素偶联物（简称 FA-MP-DOX）被用于主动肿瘤靶向。通过（1）H NMR 分析证实了该偶联物的结构。此外，还测定了该偶联物的结合效率、药物释放性能和稳定性。采用卵巢癌细胞 A2780 作为体外细胞模型，评估了细胞摄取和细胞毒性。与中性 pH（7.4）相比，FA-MP-DOX 偶联物在酸性 pH 下的 DOX 释放速度更快。在 pH 2.5、5.0 和 7.4 下孵育 30 h 后，分别释放了约 68.71%、50.08%和 26%的游离 DOX。根据 IC（50）值，与母体药物相比，该偶联物在 48 h 培养后对卵巢癌细胞 A2780 更有效。这些结果表明，FA-MP-DOX 偶联物可能是一种有前途的阿霉素载体，可用于靶向和细胞内递药。
