College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
J Liposome Res. 2012 Sep;22(3):245-53. doi: 10.3109/08982104.2012.684150. Epub 2012 May 21.
Doxorubicin, as a widely used chemotherapeutic, always causes multidrug resistance in human cancer cells. To circumvent drug resistance, we developed a novel formulation where doxorubicin hydrochloride (DOX) and chloroquine phosphate (CQ) were simultaneously loaded into liposomes by a pH-gradient method where CQ played the role of a chemical sensitizer. The various factors were investigated to optimize the formulation and manufacturing conditions of DOX and CQ coencapsulated liposomes (DCL). The resultant DCLs achieved the high encapsulation efficiency of both drugs over 90%. Further, DCLs significantly displayed resistance reversal action on a doxorubicin-resistant human breast cancer cell line (MCF-7/ADR) through the cooperation of CQ with DOX. The reversal fold of DCL with the DOX/CQ/soybean phosphatidylcholine weight ratio of 0.5:1:50 was 5.7, compared to free DOX. These results demonstrate that DCL is a promising formulation for the treatment of DOX-resistant breast cancer.
多柔比星是一种广泛应用的化疗药物，但其在人类癌细胞中常导致多药耐药。为了克服耐药性，我们开发了一种新的制剂，通过 pH 梯度法同时将盐酸多柔比星（DOX）和磷酸氯喹（CQ）载入脂质体中，其中 CQ 起到化学增敏剂的作用。我们研究了各种因素来优化 DOX 和 CQ 共包封脂质体（DCL）的制剂和制备条件。所得 DCL 对两种药物的包封效率均超过 90%。此外，DCL 通过 CQ 与 DOX 的协同作用，对多柔比星耐药的人乳腺癌细胞系（MCF-7/ADR）表现出显著的耐药逆转作用。DOX/CQ/大豆磷脂重量比为 0.5:1:50 的 DCL 的逆转倍数为 5.7，优于游离 DOX。这些结果表明，DCL 是治疗多柔比星耐药乳腺癌的一种有前途的制剂。
