Morikawa Yoshinori, Tagami Tatsuaki, Hoshikawa Akihiro, Ozeki Tetsuya
Drug Delivery and Nano Pharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University.
Biol Pharm Bull. 2018;41(6):899-907. doi: 10.1248/bpb.b17-01036.
Microfluidics is a promising system for efficiently optimizing the experimental conditions for preparing nanomedicines, such as self-assembled nanoparticles. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are promising drug carriers allowing sustained drug release. Here, we encapsulated the model drug curcumin, which has many pharmacological activities, into PLGA nanoparticles and investigated the effects of experimental conditions on the resulting PLGA nanoparticles using a microfluidics system with a staggered herringbone structure that can stir solutions through chaotic advection. The total flow rate and flow rate ratio of the solutions in the microfluidics system affected the diameters, polydispersity index, and encapsulation efficiency of the resulting PLGA nanoparticles and produced small, homogenous PLGA nanoparticles. The incorporation of polyethylene glycol (PEG)-PLGA into the PLGA nanoparticles reduced the particle size and improved the encapsulation efficiency. Initial burst release from the PLGA nanoparticles was prevented by the incorporation of PEG2000-PLGA. Curcumin-loaded PEGylated PLGA nanoparticles showed cytotoxicity similar to that of other formulations. This microfluidics system allows high throughput and is scalable for the efficient preparation of PLGA nanoparticles and PEGylated PLGA nanoparticles. Our results will be useful for developing novel PLGA-based polymer nanoparticles by using the microfluidics.
微流控技术是一种很有前景的系统，可有效优化制备纳米药物（如自组装纳米颗粒）的实验条件。聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒是很有前景的药物载体，可实现药物的持续释放。在此，我们将具有多种药理活性的模型药物姜黄素封装到PLGA纳米颗粒中，并使用具有交错人字形结构的微流控系统研究实验条件对所得PLGA纳米颗粒的影响，该系统可通过混沌平流搅拌溶液。微流控系统中溶液的总流速和流速比会影响所得PLGA纳米颗粒的直径、多分散指数和包封效率，并产生小尺寸、均匀的PLGA纳米颗粒。将聚乙二醇（PEG）-PLGA掺入PLGA纳米颗粒中可减小粒径并提高包封效率。掺入PEG2000-PLGA可防止PLGA纳米颗粒的初始突释。负载姜黄素的聚乙二醇化PLGA纳米颗粒显示出与其他制剂相似的细胞毒性。这种微流控系统具有高通量且可扩展，可用于高效制备PLGA纳米颗粒和聚乙二醇化PLGA纳米颗粒。我们的结果将有助于利用微流控技术开发新型基于PLGA的聚合物纳米颗粒。
