Ota Aoba, Mochizuki Ayaka, Sou Keitaro, Takeoka Shinji
Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
Waseda Research Institute for Science and Engineering, Waseda University, Tokyo, Japan.
Front Bioeng Biotechnol. 2023 Aug 22;11:1229829. doi: 10.3389/fbioe.2023.1229829. eCollection 2023.
Microfluidic formulation of liposomes has been extensively studied as a potential replacement for batch methods, which struggle with problems in scalability and difficulty in modulating conditions. Although microfluidic devices are considered to be able to combat these issues, an adequate replacement method has yet to be established. This paper examines the potential of a static mixer (SM) by comparing the encapsulation efficiency, loading, lamellarity, and user-friendliness with a commonly used microfluidic device, a staggered herringbone micromixer (SHM). In both devices, it was found that as the initial lipid concentration increased, the particle size increased; however, the overall particle size was seen to be significantly larger in the liposomes prepared with SM. PDI remained significantly smaller in SM, however, signifying that better control of the particle size was accomplished in SM. In addition, the encapsulation efficiency was slightly smaller in SM compared to SHM, and in both devices, the values increased as the initial lipid concentration increased. The increase in encapsulation efficiencies was significantly smaller than that of the theoretical encapsulation efficiency, and this was found to be due to the increase in lamellarity as the initial lipid concentration increased. In terms of user-friendliness, SM demonstrated significant advantages. The mixing elements could be taken out from the device, allowing for thorough cleaning of the element and device before and after experiments and ensuring experiments are conducted at virgin state in every round. Consequently, it was found that SM not only can produce uniformly distributed liposomes but has the potential to become a more practical method for liposome formulation with modifications in the mixing elements.
脂质体的微流体制备方法已被广泛研究，有望取代传统的批量制备方法，后者在可扩展性和条件调控方面存在问题。尽管微流控设备被认为能够解决这些问题，但尚未建立一种合适的替代方法。本文通过比较静态混合器（SM）与常用的微流控设备——交错人字形微混合器（SHM）的包封效率、载药量、层数和用户友好性，研究了静态混合器的潜力。在这两种设备中，均发现随着初始脂质浓度的增加，粒径增大；然而，用静态混合器制备的脂质体的总体粒径明显更大。不过，静态混合器中的多分散指数（PDI）仍然显著更小，这表明静态混合器对粒径的控制更好。此外，静态混合器的包封效率略低于交错人字形微混合器，且在两种设备中，该值均随初始脂质浓度的增加而升高。包封效率的增加明显小于理论包封效率的增加，这是由于随着初始脂质浓度的增加层数增多所致。在用户友好性方面，静态混合器具有显著优势。混合元件可以从设备中取出，便于在实验前后对元件和设备进行彻底清洁，并确保每一轮实验都在原始状态下进行。因此，发现静态混合器不仅可以制备分布均匀的脂质体，而且通过对混合元件进行改进，有潜力成为一种更实用的脂质体制备方法。
