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首页> 外文期刊>RSC Advances >Engineering docetaxel-loaded micelles for non-small cell lung cancer: a comparative study of microfluidic and bulk nanoparticle preparation
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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：非小细胞肺癌工程多西他赛负载胶束：微流控和批量纳米粒子制备的比较研究。

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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 IC _(50) 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：胶束的批量制备具有容易形成大的聚集体和不均匀的粒径分布的缺点。微流体技术显示出明显的潜力，可以解决强大的纳米医学应用中的这些挑战。在这项研究中，通过微流控和透析方法制备了装载多西他赛的PLGA-PEG-Mal基胶束，并对其理化性质进行了分析。还在非小细胞肺癌（NSCLC）细胞系A549中体外和体内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径较小，平均粒径为72±1 nm，粒径分布较窄，多分散指数（PDI）为0.072;同时，用透析法（DMD）制备的胶束具有较大的粒径（102-144 nm）和PDI（最大0.390）。更重要的是，使用微流控过程可实现很高的载药量。 DMM的IC _（50）值低于DMD。活体小鼠的全身荧光成像显示，与DMD相比，DMM在肿瘤中获得了更高的积累。 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，胶束没有引起明显的生物毒性。另外，在DMM的基础上，以Arg-Gly-Asp（RGD）为靶向剂制备靶向胶束，该靶向胶束具有较强的细胞毒性和明显的抗肿瘤功效。综上所述，由于DMM具有最佳的理化特性，其在NSCLC的治疗中可能具有明显的临床优势。因此，基于微流体技术的胶束作为结合抗癌药的有效药物递送系统是一个有前途的平台。

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