2025-02-10 作者：ZJ 来源：文献：Synergistically Improved Anti-tumor Efficacy by Co-delivery Doxorubicin and Curcumin
Polymeric Micelles
文献链接：https://pubmed.ncbi.nlm.nih.gov/25981672/
作者：Jinling Wang, Wenzhuan Ma, Pengfei Tu
原文摘要：P-gp mediated drug efflux has been recognized as a major obstacle limiting the success of cancer chemotherapy. To overcome this issue, doxorubicin (DOX) and curcumin (Cur; P-gp inhibitor and apoptosis inhibitor) co-encapsulated pegylated polymeric micelles ((DOXþCur)-
PMs) were designed, prepared and characterized to simultaneously deliver chemotherapeutic drug and multidrug resistance (MDR) modulator to tumor sites. The (DOXþCur)-PMs were spherical nano-size particle, with a loading content of 6.83%, and high colloidal stability. Codelivery micelles exhibited excellent cytotoxicity by reversing MDR, promoting cellular uptake and enhancing cellular apoptosis in MCF7/Adr cells. The tumor growth inhibitory effect of (DOXþCur)-PMs in 4T1-bearing mice was more effective compared with the combination solution of DOX and Cur and even DOX-PMs. In conclusion, simultaneous delivery of DOX and Cur by (DOXþCur)-PMs has been demonstrated to be a promising approach for overcoming MDR and improving antitumor efficacy.
PEG2000-DSPE（聚乙二醇 2000 - 二硬脂酰磷脂酰乙醇胺）能增加脂质体等纳米制剂的稳定性，延长在体内的循环时间，减少被网状内皮系统快速清除的几率。同时，其良好的亲水性可改善制剂的水溶性，提高药物的生物利用度。此外，PEG2000-DSPE 还具有较好的生物相容性，能降低对机体的不良反应，为药物的安全递送提供保障。基于此采用TPGS2000和PEG2000-DSPE两种二嵌段聚合物制备了结合DOX和Cur（P-gp抑制剂和Apoptosis 抑制剂）的混合胶束，将药物和多药耐药（MDR）调节剂传递到药用部位克服MDR，提高DOX的作用。制备过程如下：
图：用DLS测定（DOXþCur）-pms的大小分布(A)和 zeta电位(B)
采用溶剂蒸发法制备了（DOXþCur）-PMs的共传递胶束。将DOX盐酸与过量的三乙胺在甲醇中反应，获得阿霉素游离碱（DOX）。然后，将DOX、Cur、TPGS2000和PEG2000-DSPE溶解在甲醇溶液中，温和搅拌。采用旋转真空蒸发法，通过减压法去除有机溶剂。将药物聚合物膜在生理盐水中水合，搅拌然后离心，通过过滤器过滤得到（DOXþCur）-pms。
图：分别在MCF7/Adr细胞中分别孵育DOX、DOXþCur和（DOXþCur）-pms1小时和3小时后的共聚焦激光扫描显微镜（CLSM）图像。
结论：PEG2000-DSPE参与制备的共封装DOX和Cur的包封效率和稳定性高的聚合物胶束。Cur是一种化学增敏剂，可增加DOX的细胞摄取，提高MCF7/Adr细胞的效果。同时，DOX和Cur共包束在胶束中可增强体外细胞摄取和Apoptosis ，提高体内抗tumor作用。
