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Engineering docetaxel-loaded micelles for non-small cell lung cancer: a comparative study of microfluidic and bulk nanoparticle preparation

机译：用于非小细胞肺癌的工程多西紫杉醇胶束：微流体和散装纳米粒子制剂的比较研究

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Bulk preparation of micelles has the drawbacks of facile formation of large aggregates and heterogeneous particle size distribution. Microfluidic technology has shown clear potential to address these challenges for robust nanomedicine applications. In this study, docetaxel-loaded PLGA-PEG-Mal-based micelles were prepared by microfluidics and dialysis methods and their physicochemical properties were analyzed. The biological behaviors of these micelles were also investigated in the non-small cell lung cancer (NSCLC) cell line A549 in vitro as well as in vivo. Encouragingly, the mean particle size of the micelles prepared by microfluidics (DMM) was smaller, with an average size of 72 +/- 1 nm and a narrow size distribution with a polydispersity index (PDI) of 0.072; meanwhile, micelles prepared by the dialysis method (DMD) had larger particle sizes (range, 102 to 144 nm) and PDIs (up to 0.390). More importantly, significantly high drug loading was achieved using the microfluidic process. The IC50 value of DMM was lower than that of DMD. Whole-body fluorescence imaging of live mice showed that DMM achieved higher accumulation in tumors compared with DMD. DMM showed superior antitumor efficacy, with a tumor inhibition rate of 91.5%. Moreover, pathological histology analysis revealed that no evident biological toxicity was caused by the micelles. In addition, Arg-Gly-Asp (RGD) was employed as a targeting agent on the basis of DMM to prepare targeting micelles, and the targeting micelles exhibited stronger cytotoxicity and obvious antitumor efficacy. In conclusion, DMM may have obvious clinical advantages for the treatment of NSCLC due to its optimized physiochemical properties. Therefore, microfluidic technology-based micelles are a promising platform as an effective drug delivery system for incorporating anticancer agents.
机译：块状胶束的块状制备具有容易形成的大聚集体和异质粒度分布的缺点。微流体技术表明，为强大的纳米医疗应用解决这些挑战而明显潜力。在该研究中，通过微流体和透析方法制备了多西紫杉醇的PLGA-PEG-MAR基胶束，并分析了它们的物理化学性质。在体外，在非小细胞肺癌（NSCLC）细胞系A549中也研究了这些胶束的生物学行为。令人鼓舞的是，通过微流体（DMM）制备的胶束的平均粒子尺寸较小，平均尺寸为72 +/-1nm，并且具有0.072的多分散指数（PDI）的窄尺寸分布;同时，通过透析法（DMD）制备的胶束具有较大的粒度（范围，102至144nm）和PDI（高达0.390）。更重要的是，使用微流体过程实现了显着高的药物载荷。 DMM的IC50值低于DMD。与DMD相比，活小鼠的全体荧光成像表明DMM在肿瘤中取得了更高的积累。 DMM显示出优异的抗肿瘤功效，肿瘤抑制率为91.5％。此外，病理组织学分析表明，胶束没有明显的生物毒性。另外，基于DMM使用Arg-Gly-Asp（RGD）作为靶向剂以制备靶向胶束，并且靶标胶束表现出更强的细胞毒性和明显的抗肿瘤功效。总之，由于其优化的理化性质，DMM可能具有明显的临床优势，用于治疗NSCLC。因此，基于微流体技术的胶束是一种希望的平台，是一种用于掺入抗癌剂的有效药物递送系统。

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  • 来源
    《RSC Advances》 |2018年第56期|共17页
  • 作者

    Bao Yuchen; Deng Qinfang; Li Yongyong; Zhou Songwen;

  • 作者单位

    Tongji Univ Shanghai Pulm Hosp Sch Med Dept Med Oncol Shanghai 200433 Peoples R China;

    Tongji Univ Shanghai Pulm Hosp Sch Med Dept Med Oncol Shanghai 200433 Peoples R China;

    Tongji Univ Shanghai Peoples Hosp 10 Sch Med Inst Biomed Engn &

    Nanosci Shanghai 200092 Peoples R China;

    Tongji Univ Shanghai Pulm Hosp Sch Med Dept Med Oncol Shanghai 200433 Peoples R China;

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