Bao Yuchen, Deng Qinfang, Li Yongyong, Zhou Songwen
Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine Shanghai 200433 China
Shanghai Tenth People's Hospital, The Institute for Biomedical Engineering & Nanoscience, Tongji University School of Medicine Shanghai 200092 China
RSC Adv. 2018 Sep 14;8(56):31950-31966. doi: 10.1039/c8ra04512g. eCollection 2018 Sep 12.
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 as well as . 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 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.
大量制备胶束存在易形成大聚集体和粒径分布不均一的缺点。微流控技术已显示出在解决这些挑战以实现强大的纳米医学应用方面的明显潜力。在本研究中，通过微流控和透析方法制备了载有多西他赛的基于聚乳酸-羟基乙酸共聚物-聚乙二醇-马来酰亚胺（PLGA-PEG-Mal）的胶束，并分析了其理化性质。还在非小细胞肺癌（NSCLC）细胞系A549中研究了这些胶束的生物学行为。令人鼓舞的是，通过微流控制备的胶束（DMM）平均粒径较小，平均尺寸为72±1 nm，粒径分布窄，多分散指数（PDI）为0.072；同时，通过透析法制备的胶束（DMD）粒径较大（范围为102至144 nm），PDI高达0.390。更重要的是，使用微流控工艺实现了显著高的载药量。DMM的半数抑制浓度（IC）值低于DMD。对活小鼠的全身荧光成像显示，与DMD相比，DMM在肿瘤中的蓄积更高。DMM显示出优异的抗肿瘤疗效，肿瘤抑制率为91.5%。此外，病理组织学分析表明胶束未引起明显的生物毒性。此外，基于DMM采用精氨酸-甘氨酸-天冬氨酸（Arg-Gly-Asp，RGD）作为靶向剂制备靶向胶束，靶向胶束表现出更强的细胞毒性和明显的抗肿瘤疗效。总之，DMM由于其优化的理化性质，在治疗NSCLC方面可能具有明显的临床优势。因此，基于微流控技术的胶束作为一种有效的药物递送系统来包载抗癌药物是一个有前途的平台。
