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首页> 外文期刊>RSC Advances >Co-delivery of doxorubicin and itraconazole by Pluronic? P123 coated liposomes to enhance the anticancer effect in breast cancers
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Co-delivery of doxorubicin and itraconazole by Pluronic? P123 coated liposomes to enhance the anticancer effect in breast cancers

机译：Pluronic可共同递送阿霉素和伊曲康唑？ P123涂层脂质体可增强乳腺癌的抗癌作用

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To date, the combinational cancer therapy of anticancer and antiangiogenic agents represents a promising strategy to improve antitumor outcomes in clinics. However, combination therapy with drugs having distinct properties, such as solubility, limits the likelihood of simultaneous delivery. In our study, we aimed to develop a codelivery nanoparticulate system of hydrophilic doxorubicin (DOX) and hydrophobic itraconazole (ITZ) using liposomes coated with Pluronic? P123 (ITZ/DOX-PLip). The prepared ITZ/DOX-PLip exhibited a unimodal size distribution and high loading efficiency with sustained release profiles. Furthermore, cytotoxicity against 4T1 murine breast cancer cells and cellular uptake results revealed that the inhibitory effect of ITZ/DOX-Plip on tumor growth was superior to that of free DOX or DOX-loaded liposome (DOX-Lip), which was primarily attributed to the significantly higher intercellular DOX content. Cytotoxicity against HUVEC and wound healing tests confirmed that ITZ and ITZ formulations could inhibit the growth and migration of endothelial cells. In addition, in xenograft 4T1 bearing BALB/c mice, biodistribution experiments revealed that higher drug accumulation in tumors and decreased distribution in heart were observed for ITZ/DOX-PLip as compared to free DOX. Remarkably, ITZ/DOX-PLip significantly reduced tumor volume, tumor weight, liver metastasis and microvessel density in comparison with the same dose of ITZ injection or DOX-Lip. Overall, this Pluronic? P123 modified liposome-based codelivery system represents a promising nano-platform for combination therapy in cancers.
机译：迄今为止，抗癌和抗血管生成剂的联合癌症治疗代表了一种改善临床抗肿瘤效果的有前途的策略。但是，与具有不同性质（例如溶解度）的药物联合治疗会限制同时给药的可能性。在我们的研究中，我们旨在使用涂有Pluronic？脂质体的脂质体开发亲水性阿霉素（DOX）和疏水性伊曲康唑（ITZ）的代码传递纳米颗粒系统。 P123（ITZ / DOX-PLip）。制备的ITZ / DOX-PLip具有单峰尺寸分布和高负载效率，并具有持续释放曲线。此外，针对4T1鼠乳腺癌细胞的细胞毒性和细胞摄取结果显示，ITZ / DOX-Plip对肿瘤生长的抑制作用优于游离DOX或负载DOX的脂质体（DOX-Lip），这主要归因于细胞间DOX含量明显更高。针对HUVEC的细胞毒性和伤口愈合测试证实ITZ和ITZ制剂可以抑制内皮细胞的生长和迁移。此外，在带有异种移植4T1的BALB / c小鼠中，生物分布实验表明，与自由DOX相比，ITZ / DOX-PLip观察到了更高的药物在肿瘤中的蓄积和心脏中分布的减少。值得注意的是，与相同剂量的ITZ注射剂或DOX-Lip相比，ITZ / DOX-PLip显着降低了肿瘤体积，肿瘤重量，肝转移和微血管密度。总的来说，这是Pluronic吗？ P123修饰的基于脂质体的代码传递系统代表了一种有前途的纳米平台，可用于癌症的联合治疗。

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