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Synergistic Combinations of Multiple Chemotherapeutic Agents in High Capacity Poly(2-oxazoline) Micelles

机译:高容量聚(2-恶唑啉)胶束中多种化学治疗剂的协同组合

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摘要

Many effective drugs for cancer treatment are poorly water-soluble. In combination chemotherapy, needed excipients in additive formulations are often toxic and restrict their applications in clinical intervention. Here, we report on amphiphilic poly(2-oxazoline)s (POx) micelles as a promising high capacity delivery platform for multi-drug cancer chemotherapy. A variety of binary and ternary drugs combinations of paclitaxel (PTX), docetaxel (DTX), 17-allylamino-17-demethoxygeldanamycin (17-AAG), etoposide (ETO) and bortezomib (BTZ) were solubilized in defined polymeric micelles achieving unprecedented high total loading capacities of up to 50 wt.% drug per final formulation. Multi-drug loaded POx micelles showed enhanced stability in comparison to single-drug loaded micelles. Drug ratio dependent synergistic cytotoxicity of micellar ETO/17-AAG was observed in MCF-7 cancer cells and of micellar BTZ/17-AAG in MCF-7, PC3, MDA-MB-231 and HepG2 cells.
机译:许多有效的癌症治疗药物可溶性差。在组合化疗中,添加剂配方中所需的赋形剂通常毒性并限制其在临床干预中的应用。在这里,我们报道两亲性聚(2-恶唑啉)S(POX)胶束作为多药物癌症化疗的有希望的高容量递送平台。各种二元和三元药物组合的紫杉醇(PTX),多西紫杉醇(DTX),17- allylamino-17-Demethoxygeldanamycin(17-AAG),依托普苷(ETO)和Bortezomib(BTZ)中溶解于所定义的聚合物胶束,实现前所未有的高总装载能力高达50重量%。每最终配方的药物%。与单药载胶束相比,多药物负载痘胶束显示出增强的稳定性。在MCF-7癌细胞和MCF-7,PC3,MDA-MB-231和HEPG2细胞中,在MCF-7癌细胞和胶束BTZ / 17-AAG中观察到胶束的药物比依赖于胶束entO / 17-AAG的协同细胞毒性。

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